research paper topics about schizophrenia

183 Schizophrenia Essay Topics & Examples

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🔝 Top 10 Schizophrenia Research Topics for 2024

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Brain Abnormalities in Schizophrenia
Risk Factors of Adolescent Schizophrenia
Cognitive Impairment in Schizophrenia Patients
Family Support in Schizophrenia Management
Ways of Enhancing Social Skills in Schizophrenia
Schizophrenia and Comorbid Medical Conditions
Early Detection and Intervention in Schizophrenia
Genetic and Environmental Factors in Schizophrenia
The Relationship between Schizophrenia and Substance Use
Efficacy of Antipsychotic Medicines and Side Effects
Schizophrenia: An Informative View It discusses the symptoms of the disorder, the cause, and the impact it has on both the individual suffering from it and the people surrounding the victim, both within and outside the family unit.
Schizophrenia in The Center Cannot Hold by Elyn Saks Nevertheless, in college, Saks faced stress due to the need to study, communicate, and care about herself and was left without the support of the Center, which led to the first episode of acute psychosis.
Freud’s Psychoanalysis for Schizophrenia Patients In this paper, the author’s approaches to this ailment are considered, and the ways of applying the specific observations of human behavior are discussed. Freud’s contribution to the development of psychoanalysis is significant, and his […]
Schizophrenia in ‘A Beautiful Mind’ Film The main symptom of a schizophrenic patient depicted in the film is the patient’s inability to distinguish between the real world and the subconscious pattern created within the imaginations of his mind.
Dimensional Approaches to Schizophrenia and their Inclusion in the DSM-V The inclusion of the dimensional diagnosis of schizophrenia and other disorders to DSM-V will help to avoid some of the problems that are currently faced by the system.
The Movie “A Beautiful Mind” and Display of Schizophrenia This paper offers an in-depth analysis of the movie A Beautiful Mind to ascertain its display of schizophrenia as well as societal and cultural attitudes towards the disorder.
Schizophrenia Explained by “A Beautiful Mind” It is a disease which can emotionally devastate the [patient as well as the relatives and the loved ones of the patient causes the patients to have hallucinations as well as delusions and even in […]
A Beautiful Mind: Understanding Schizophrenia and Its Impact on the Individual and the Family The psychological disorder presented in the movie refer to one of the most common of schizophrenia paranoia. The disorder, however, is still subjected to experimental treatments by means of medications and psychotherapy.
Schizophrenia Patients Using Atypical Medication The research procedure follows a timed experiment with several trials beginning with a fixation point displayed in the middle of the black rectangle. A participant’s task is to identify accurate locations of the stimuli after […]
Schizophrenia and Its Effects on the Brain This shows that functional variations are not a product of long consequences of the condition or therapy for the disorder, just like the structural alterations in gray matter and white matter.
Negative versus Positive Symptoms of Schizophrenia Schizophrenia is a condition that hinders the ability of a person to think, feel, and act. In Schizophrenia, a decrease or absence of normal motivational and interest-related behaviors or expressions are referred to as negative […]
The Brief Psychotic Disorder, Schizophreniform Disorder, and Schizophrenia People with “delusions, hallucinations, and disorganized behavior, with a return to normal functioning over a short time span” are diagnosed with a brief psychotic disorder.
Schizophrenia and Schizoaffective Disorder He is calm and cooperative. There is no evidence of any suicidal or homicidal ideation, and he denies them as well.
Schizophrenia: Causes and Symptoms People with this condition can live full lives and perform independently because of the accessibility of medicine, counseling, and support. Additionally, the ideal way to perceive Schizophrenia is when it is promptly diagnosed and treated.
Schizophrenia: Neurochemical Theories and Medications The dopamine theory regarding schizophrenia, the serotonin theory of depression, and the glutamate theory will get discussed in detail in this paper. The dopamine hypothesis of schizophrenia holds that the overall neurotransmitters associated with dopamine […]
Schizophrenia and Bipolar Disorder Portrayal in Mass Media Thus, the portrayal of the disorder in the media is the mix of symptoms that belong to bipolar I and II disorders in the textbook.
Indian, Chinese, and American Approaches to Treating Schizophrenia Thus, the perception of mental illnesses in Chinese traditional medicine should be discussed it will benefit the patients and reduce the destructive effects such disorders as schizophrenia may have on one’s life.
Health Information: Schizophrenia The critical components that I used to evaluate the sites are the owners, mission, references, and information review. The benefits of WebMD are that it mentions the author’s name and the person who medically reviewed […]
Schizophrenia Spectrum and Psychosis Disorders Management The psychopharmacology of risperidone shows the correlation between the drug’s impact on the brain and the behavior of patients. The FDA addresses the management of risperidone based on its class and its mechanism of action.
Schizophrenia: Case Analysis Paper The purpose is to inform the reader about a comprehensive case study with a schizophrenia diagnosis and the rationale for a nursing care plan.
The Current Concept of Schizophrenia Is Neither Valid and Useful The primary research question is ‘Is the current concept of schizophrenia valid and useful?’ Hence, it is crucial to evaluate the empirical basis to answer the question and discuss the alternative system.
Plan for Management of Patient with Schizophrenia and Heart Disease About 1% of the world’s population suffers from schizophrenia About 0. 7% of the UK population suffers from schizophrenia Schizophrenia can manifest any time from early adulthood onwards, but rarely when a person is below […]
Quality of Life With Schizophrenia The main difference between the former and new guidelines in patients’ professional and personal life will only be that people with schizophrenia will have to consider the symptoms of their illness and maintain a distance […]
Schizophrenia: The Etiology Analysis Disrupted epigenomic regulation in response to environmental triggers leads to decreased brain function and the onset of schizophrenia. The Khavari & Cairns, article focuses on the epigenomic factors that contribute to the development of the […]
Schizophrenia as a Chronic Mental Disorder The first signs of the disease began to appear at the age of 28, which, according to his friend, coincided with the patient’s loss of a loved one.
Schizophrenia and Its Effects on the Lives of Patients Schizophrenia is a mental disorder that affects the lives of patients diagnosed with the condition on multiple levels, as evident from the individual in question.
Schizophrenia Diagnostics and Its Challenges In addition to the core symptoms of hallucinations, delusions, or persistent disorganized speech, schizophrenia may be manifested through psychosis, which accounts for the majority of acute admissions to the inpatient setting.
Schizophrenia: Symptoms and Therapy Schizophrenia is a complex condition involving a number of cognitive, behavioral and emotional symptoms, all of which can present differently depending on the person. In addition, there are a number of symptoms that can help […]
Schizophrenia Disorder: Definition, Treatment, and Medication Schizophrenia is linked to anatomical and functional alterations in the pallium, the layer of the unmyelinated neurons, as well as variations in the networks in the middle of cortical areas.
Schizophrenia: Cause, Consequence, Care Considering the assessment above, the diagnosis of paranoid schizophrenia can be established due to Caroline’s concerns about being a target for her social environment.
Analysis of Article Related to Schizophrenia Treatment The objective of the study is to evaluate the effectiveness and safety application of cannabidiol as an adjunctive treatment for patients with schizophrenia.
Neuroscience: Schizophrenia and Neurotransmitters From the definition of neurotransmitters, it is clear that schizophrenia is caused by the irregular functioning of neurotransmitters. Physical abnormalities in the brain have been suspected to be causes of schizophrenia.
Treatment Plan For Schizophrenia Patient Bill will fully recover and be in a position to perform the activities of the daily living on his own. Bill complies with the treatment regimen because treatment will help him recover and be in […]
Mental Health: Analysis of Schizophrenia In the early years, signs related to the disease were said to be resulting from possession of evil spirits. The history of development in respect to mental health can be traced to antiquity.
Paranoid Schizophrenia: Psychosocial Rehabilitation The behavior of being a social loner is reinforced by the indoor equipments that motivate his stay in the house. Barhof et al, explains that recognition of the value or importance of change is wholly […]
Principles and Practice of Psychosocial Rehabilitation: Schizophrenia The objective of this study was to evaluate the literature accumulated so far and address the issues surrounding the principles and practice of Psychosocial Rehabilitation.
Schizophrenia and Primary Care in Britain The illness causes distress in the form of severe suffering for the patient, his family and friends. The annual costs for care and treatment of schizophrenia in the United Kingdom in the 1990s were 397 […]
The Schizophrenia Drugs: Lithium and Abilify Lithium overdose affects primarily two systems of the human body: the central nervous system and the kidneys since it is through the latter that the drug is excreted from the body.
Collaborative Care in a Schizophrenia Scenario For example, the social worker will be in a position to emphasize the human dimensions of the problem, such as Simon’s preferences and social aspirations.
Alcoholism and Schizophrenia: Interconnection In addition to its physical effects on the chronic drinker’s body, alcohol is associated with a variety of mental impairments. Alcoholic dementia and Wernicke-Korsakoff syndrome are among the most prominent concerns in the matter. The former is a blanket term for a variety of cognitive deficiencies caused by the substance. The latter is a two-stage […]
“Schizophrenia: A Sibling’s Tale” by Stephan Kirby The primary purpose of this article seems to inform the readers about the effective strategies that can be implemented in order to help the families of the affected people to go through a number of […]
Schizophrenia and Workplace Behaviors Besides, their condition and performance at work may be significantly improved in case of a proper help from the company’s leadership.
Schizophrenia and Health Strategy Proposal The use of qualitative analysis is thus justified, since the amount of detail and quality of information required would only be provided using this method.
Schizophrenia and Biological Therapeutic Approach The level of social stigma associated with this condition has been identified as a major obstacle to the recovery of patients from this condition.
Schizophrenia: An Abnormal Human Behavior Despite there not being a cure for the disorder as yet, there are current treatments available and meant to eliminate the majority of symptoms associated with the disorder thus enabling such individuals to live healthy […]
Schizophrenia & Neurosis and Lifespan Development The learning objectives are to comprehend worrying conduct in the scope of the growth missions, series, and procedures that show human development.
Schizophrenia Diagnostic Assessment As is mentioned above, the client does not understand or is not able to see the original appearance of objects and people around her.
Analyzing Psychological Disorders: Schizophrenia Nevertheless, the damage to the brain as a result of this disorder seems to target two main areas: the frontal lobe, and the parietal cortex.
Schizophrenia Study and Rehabilitation Outcome In fact, the results of this prospective study can reasonably be projected to the universe of Germans with mental disorders only if Rehabilitation Psychisch Kranker in the city of Halle is a kind of secondary […]
Theme of Schizophrenia in “Slaughterhouse-Five” by Kurt Vonnegut The Tralfamadorian subplot includes a vision of the end of the world and the perpetuation of war, but these seem distant threats compared with the miseries of battlefield.
Schizophrenia in Adults: Causes, Diagnosis, and Management Among the usual characteristics of schizophrenia is low motivation; which consequently makes the victim withdraw from other members of the society.”Although studies have shown that, women are equally likely to develop the mental disorder as […]
Schizophrenia Causes, Symptoms, and Risk Factors This paper aims to research and analyze the causes, symptoms and the risk factors associated with the mental disease and discuss some of the prevention measures of the disease.
Haldol and Negative Symptoms of Schizophrenia Very often this disease is treated with the help of haloperidol, a kind of injection used as a medicine against brain disorders and psychotic states.
Schizophrenia: The Role of Family and Effect on the Relations The role of family members and other social support is essential and form part of the management of this illness. The illness causes the others in the family to have stress.
Schizophrenia as a Common Mental Disorder Before a patient is diagnosed to have schizophrenia, the person must have two or more of the following symptoms for at least a month according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth […]
Delusional “Pseudotranssexualism” in Schizophrenia But it was in the middle of the twentieth century that the name transsexualism was fixed for this disorder for the first time by Cauldwell and after a few years Benjamin in the US and […]
Schizophrenia Symptoms, Etiology, and Treatment The treatment as well as the prognosis for recovery is highly dependent on the stage in which schizophrenia is diagnosed and the age of first onset.
Schizophrenia Causes and Treatment Analysis There exist several theories about the causes of schizophrenia, the most convincing of them are: the theory of genetic predispositions, the theory of prenatal or vital antecedents and the theory of social and environmental causes.
Schizophrenia: Characteristics, Types and Symptoms This disease is a type of brain disease which if remain unnoticed affects the entire personality and life of the patient.
Schizophrenia: Biological & Environmental Causes The indications of schizophrenia are varied but the results are the same, causing a breakdown of individuality and the consequent inability of the personage to purpose in reality.
Schizophrenia and Its Special Symptoms Talking to the patients in a way that could enhance their hopes in life and activities they usually engage in is one way of reducing patients’ overwhelmed, as well as keeping them with the hope […]
Can Cannabis Cause Schizophrenia? Regarding this assignment, I am going to address the importance of this topic in the field of addiction and healthcare, assessing the research that suggests that cannabis plays a role in schizophrenia and the strengths […]
People With Schizophrenia Diagnosis in Prisons As a result, the behavior of the individuals with the condition is a threat to the members of the family and the society.
Schizophrenia Symptoms and Treatment Complications Schizophrenia is one of the most complex examples of these disorders because it leads to the inability to live independently and hold a job.
Paranoid Schizophrenia in “A Beautiful Mind” The film A Beautiful Mind depicts the impact of progressive paranoid schizophrenia on the mathematician John Nash and the burden that it places on social and personal relationships.
Schizophrenia: History and Diagnosis The process of diagnosing involves a comprehensive assessment of the patient’s symptoms, in which a specialist searches for the symptoms of schizophrenia and other disorders, which need to be ruled out for the diagnosis to […]
Schizophrenia Diagnosis, Planning and Treatment Peter is 18 years old He lives at home with his parents. The patient has gained 20 pounds without any diet changes His glucose is at 145 He has not been taking his Olanzapine […]
Schizophrenia Research: Ethical Principles and Steps The issue of beneficence is also put into consideration to ensure the research is done to improve the well being of the subjects and the society at large.
Prevention of Suicide in People with Schizophrenia As a strategy to prevent suicide in schizophrenic patients, the drugs are aimed at controlling the symptoms associated with the condition.
Readmissions in Schizophrenia and Reduction Methods After this, the regression model will be developed applying the variables associated with predictors of readmission and the dichotomous variable as the outcome.
Schizophrenia Therapy: “People Matter” by Marley The study indicates how the targeted respondents supported the “use of different interpersonal interactions towards reducing the symptoms associated with schizophrenia”. This author supports the use of interpersonal interactions in every patient with schizophrenia.
Schizophrenia Effects on Patient Development This essay explores schizophrenia in a bid to understand what it really is, how it affects the development and relational abilities of its victims, and why these effects qualify it as a mental disorder.
Courtesy Stigma: Relatives of Schizophrenia Patients The quota sampling method was used in the research survey. In regards to the analytic strategy, the inductive formation of categories was used to analyze the transcripts.
Schizophrenia Symptomatology and Misdiagnosis Although it was previously believed that the incidence and prevalence of schizophrenia in men and women were approximately the same, newer studies point out that the use of more restrictive criteria for diagnosis results in […]
Schizophrenia and Cognitive Therapy Interventions The onset of the mental disorder usually occurs in the first half of life; however, many episodes of schizophrenia have been registered beyond the age of 60 years.
Schizophrenia and Bipolar Disorder in Children and Adolescents It is acknowledged by the researchers that the symptoms indicate the possibility of bipolar disease and not schizophrenia. Psychiatric and physiological factors, among others, contribute to the prevalence of self-harm in children and young people.
Schizophrenia Drugs’ Mechanism of Action In the case of M.Y.is can be useful to prescribe a second-generation antipsychotic, and if it proves to be ineffective, clozapine can be used.
Schizophrenia Treatment: 25-Year-Old Male Patient The symptom of social isolation also contributes to the development of schizophrenia in Mr. Dashiell to identify the cause of the condition.
Schizophrenia Hypothesis and Treatment The dopamine theory hypothesizes that the activation of post-synaptic dopamine receptors in the mesolimbic pathway of the brain increases dopaminergic activity, resulting in positive symptoms delusions and hallucinations.
The Diagnostic Concept of Schizophrenia Cultural and historical contexts have largely influenced the perception of this mental disorder, and the assessment of this disease and its features in different cultures is not the same.
Schizophrenia: Diagnosis and Treatment Approaches A detailed analysis of the factors that affect the patient’s condition, including the internal and the external ones, must be mentioned as one of the essential strengths of the studies that have been conducted on […]
Schizophrenia in Young Men and Women Thus, the research of the problem among the young people is the primary task. The feelings of people with schizophrenia are contradictory and uncertain.
Paranoid Schizophrenia in “A Beautiful Mind” Movie John Nash is the protagonist in the movie, A Beautiful Mind. The movie did a good job of depicting the disorder in John Nash.
Schizophrenia, Ethical and Multicultural Issues For instance, the assumption that the absence of evidence implies the same outcomes as the actual absence of the disorder symptoms often hinders the process of determining and addressing schizophrenia in patients.
Schizophrenia, Its Symptoms, Prevalence, Causes Noteworthy, hallucinations and delusions are reflections of the distortions of the human mind, which in turn causes distortions of the person’s perceptions and interpretations of reality.
Pharmacological & Psychotherapeutic Schizophrenia Interventions The use of clozapine is a medical intervention that targets the biological functioning of patients by blocking serotonin receptors and thus bringing about the release of dopamine receptors in specific parts of the brain.
Schizophrenia Effects on Patient, Caregiver, Society The purpose of this paper is to discuss the effects of schizophrenia on the victim, caregiver, as well as the society.
Schizophrenia and the Reduction of Readmissions Thus, this research will be rather useful because it will discuss the effectiveness of self-management programs for people with schizophrenia and their influence on the reduction of readmissions.
Self-Management Programs for Schizophrenia Therefore, the significance of the problem that is reviewed in this paper consists in the fact that the approaches to the treatment of schizophrenia can be optimized.
Schizophrenia and Frequent Readmission Rates This literature review is focused on the exploration of self-management programs for patients with schizophrenia and their effectiveness in terms of the reduction readmission rates and the overall management of the condition.
Schizophrenia and Its Functional Limitation The situation advances in severity with the age of the patient. This condition may affect work, social, training, and interpersonal relations and skills among people with the schizophrenia condition.
Schizophrenia and Self-Management Programs In order to collect the data for further analysis that will help to answer the defined research question, it will be necessary to conduct the study allowing the researchers to track changes in behavior and […]
Schizophrenia Readmissions Reduction: Data Analysis A simple random sampling technique will be used to select participants, and it implies that each respondent will be randomly chosen to take part in the study to avoid bias and ensure the validity of […]
Readmission Rates in Schizophrenia Patients The purpose of this paper is to propose a research analyzing the frequency of admission rates among patients with schizophrenia treated with long-acting injectable antipsychotics or with oral antipsychotics.
Eating Disorders, Insomnia, and Schizophrenia Of course, this readiness does not exclude the necessity to identify such people and provide the necessary treatment to them, which is proved to be effective.
Schizophrenia as an Extreme Form of Schizotypy The use of Meehl’s model to expose extreme forms of schizotypy as a manifestation of schizophrenia also informs the findings of this paper. Nonetheless, the similarities between schizophrenia and schizotypy do not show that one […]
Schizophrenia: Psychiatric Evaluation and Treatment Plan The purpose of this paper is to examine the symptoms characteristic for Oscar in order to determine whether it is necessary to conduct the psychiatric evaluation for the young man and propose the plan of […]
Schizophrenia – Mental Health Disorder The neurotransmitters at the ending of the nerve cells transmit messages from one area to another nerve cell in the body.
Schizophrenia: Symptoms and Treatment The positive symptoms of the disease incorporate hallucinations associated with hearing, illusions, and disordered language and behavior. The symptoms of schizophrenia captured in the DSM IV TR includes illusions, hallucinations, and disordered language.
Undifferentiated Schizophrenia: Sally’s Case Sally could have inherited some patterns of the disease from her maternal grandfather and her mother’s continued smoking patterns and flu during her pregnancy.
Schizophrenia Patients Biochemical and Behavioral Changes It is also important to note that microscopic studies on the tissues of brain have shown slight variations in the number of cells of the brain and their distribution patterns. Biochemical changes in the brain […]
Schizophrenia and Delusional Disorder For example, a range of scholars have attempted to identify schizophrenia and the delusional disorder as phenomena. Therefore, the instances of delirium must be viewed as possible indicators of schizophrenia.
Psychiatric Issues: Schizophrenia’s Demystify The web is an internet community that is dedicated to the provision of high-quality data, elucidation, and assistance to the kin, providers, and persons that have been impacted by the condition.
Non-Clinical Indicators in Patients with Schizophrenia The collaboration between the clinicians and the family is beneficial to the patient especially in administering the daily routines of the patient.
Schizophrenia: Pathophysiology and Treatment The treatment methods commonly in the application are based on a clinical research that has been conducted on the disease as well as on the experience of the physician on the treatment of the disease.
Schizophrenia: Description, Development and Treatment According to Van Dyke, schizophrenia begins to develop in the early adulthood years of the victim from the age of 15 to 30 years.
A Critical Examination of the Link between Nicotine Dependence and Schizophrenia Over the years, there have been strong indications that heavy cigarette smoking can be linked to schizophrenia and that smoking may have a connection to the neurobiology of schizophrenic illness.
Schizophrenia Genetic and Environmental Factors The research paper explores schizophrenia by providing a general overview, a comprehensive discussion of clinical synopsis, genetics and environmental factors in relation to schizophrenia, limitations of the methods of analyses, and a clear demonstration of […]
Childhood Schizophrenia: Causes and Management of This Mental Disorder Hardman et al.are of the view that the risk of a child suffering from this condition is one percent when there are no recorded cases of the condition in the family.
Smoking as Activity Enhancer: Schizophrenia and Gender Once learning the effects which nicotine has on people’s health and the relation between gender and schizophrenia, one can possibly find the ways to prevent the latter and to protect the people in the high-risk […]
Clinical and Neuropsychological Characteristics in Subjects With Schizophrenia The need to understand the complex interplay between a number of variables, including genetics, environmental factors, clinical, psychological and social processes, in the development of brain disorders and the resultant behavioural and cognitive deficiencies informed […]
Psychological Classification of Schizophrenia The paper is composed of a matrix that gives detailed information on the major DSM IV-TR categories of schizophrenia and psychosis, and lifespan development as well as the various classifications of schizophrenia and psychosis, and […]
Cognitive Behavioural Therapy in Schizophrenia The basic idea in cognitive therapy is the fact that the cognitive aspect of esteem, the way we perceive problems, the world, and other mundane aspects of life like expectations and beliefs are chief determinants […]
Schizophrenia a Psychological Disorder The main purpose of this research study was to investigate the relationship between Schizophrenia and reading impairments that are usually experienced by individuals when assessed in terms of Oculomotor Control and phonological Processing The research […]
Homelessness and Schizophrenia It is essential to consider that lack of a proper home can exert pressure in an individual, to the extent of mental burdening.
Should Persons Suffering From Schizophrenia Be Forced to Take Medications? Though many studies have pointed out that its causes are poorly understood, Dora is of the view that it results from the interplay of the immediate environment that a person is exposed to and the […]
Bipolar Disorder and Schizophrenia Genetically, an alteration in the serotonin, dopamine and glutamate genes may be the cause of the disease. Therefore, the close interactions of genetic, psychological and environmental factors lead to severe cases of bipolar disorder.
Schizophrenia, Psychosis and Lifespan Development Schizophrenia is a complicated condition not only due to its nature but also due to the fact that it results from a wide range of factors.
Diagnosis and Treatment of the Schizophrenia The prevalence rate of the disease is around 1% in the whole world and despite the fact that its rate is higher among the poor; there is no much difference from one culture to another. […]
Physical Health and Its Relations to Schizophrenia Smith is the fact that the disease got him at a time in life when he wanted to settle in marriage and due to the changes brought about by the mental disorder, he lost his […]
Neurological Disorder: Effects of Schizophrenia on the Brain and Behavior Furthermore, as identified earlier, the neurological basis of the disorder may also involve abnormalities in the structure of the forebrain, the hindbrain and the limbic system.
What Makes Schizophrenia One of the Worst Mental Illnesses?
Are Bipolar Disorder and Schizophrenia Neuroanatomically Distinct?
What Predicts Stigmatization About Schizophrenia?
How and Why Affective and Reactive Virtual Agents Will Bring New Insights on Social Cognitive Disorders in Schizophrenia?
What Do Visual Illusions Teach Us About Schizophrenia?
Can Neurostimulation Prevent the Risk of Alzheimer’s Disease in Elderly Individuals With Schizophrenia?
How Can Nurses Deal With a Patient With Paranoid Schizophrenia?
What Is Connection Between Schizophrenia and Social Isolation?
Are Continuum Beliefs About Psychotic Symptoms Associated With Stereotypes About Schizophrenia?
What Is the Link Between Drug Addiction and Underdiagnosed Schizophrenia?
How Does Gray Matter Effect Schizophrenia and Bipolar?
What Is Schizophrenia Disorder?
Can N-Methyl-D-Aspartate Receptor Hypofunction in Schizophrenia Be Localized to an Individual Cell Type?
How Should People With Schizophrenia Be Treat?
Are Patients With Schizophrenia Impaired in Processing Non-emotional Features of Human Faces?
How Does Schizophrenia Affect Development and Aging?
Did Andrea Yates Have Schizophrenia?
How Does Schizophrenia Affect the Lifespan?
Are Patients With Schizophrenia Spectrum Disorders More Prone to Manifest Nocebo-Like-Effects?
How Does the Environment Influence Schizophrenia and Possible Prevention?
Does Co-morbid Obsessive-compulsive Disorder Modify the Abnormal Language Processing in Schizophrenia Patients?
How Will the Mild Encephalitis Hypothesis of Schizophrenia Influence Stigmatization?
Are People With Schizophrenia Dangerous and Unpredictable?
Does Non-adherence Increase Treatment Costs in Schizophrenia?
What Are the Major Main Barriers to Treatment of Schizophrenia?
Is Schizophrenia an Incurable Mental Illness?
How Do Genetic Factors Contribute to the Development of Schizophrenia?
Is Any Particular Race More Vulnerable to Schizophrenia?
How Does Schizophrenia Affect People Who Live In States That Opted Out of the State Healthcare Exchanges?
Is Schizophrenia a Genetically Transmittable Illness?
How Do Environmental Factors Contribute to the Development of Schizophrenia?
What Are the Most Effective Pharmacological Interventions for Managing Positive and Negative Symptoms of Schizophrenia?
How Does Early Intervention Impact the Long-Term Outcomes of Individuals with Schizophrenia?
What Are the Most Common Cognitive Deficits Experienced by Schizophrenia Patients?
How Can Dual Diagnosis Treatments for Substance Use and Schizophrenia Be Optimized?
What Are the Treatment Considerations for Managing Schizophrenia in Young Adults?
How Can Family Psychoeducation and Support Programs Help Improve Treatment and Outcomes in Schizophrenia?
What Are the Social Functioning Difficulties Faced by Individuals with Schizophrenia?
How Can Holistic Care Approaches Help Address Physical Health Comorbidities Associated with Schizophrenia?
How Can Neuroimaging and Brain Research Advancements Contribute to Our Understanding of Schizophrenia?
A Multimedia Presentation Explaining the Neurobiological Basis of Schizophrenia
An infographic that Educates the Public about Early Warning Signs and Symptoms of Schizophrenia.
A Survey Assessing the Awareness and Understanding of Schizophrenia in the School Community.
Video Simulation Demonstrating the Experiences of Individuals Living with Schizophrenia
Plan of a Mental Health Awareness Event to Reduce the Stigma Surrounding Schizophrenia
Research Paper on the Impact of Family Support on Improving Outcomes of Schizophrenia Patients
Interviews with Schizophrenia Patients and Their Families
A Classroom Presentation on the Connection Between Creativity and Schizophrenia
Literature Review on the Effectiveness of Cognitive Remediation Interventions for Schizophrenia
Mental Health Awareness Campaign Focused on Schizophrenia
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30 schizophrenia research topics, rachel r.n..

September 9, 2022
Essay Topics and Ideas

Schizophrenia is a mental disorder that affects how a person thinks, feels, and behaves. People with schizophrenia may seem like they have lost touch with reality. Although there is no cure for schizophrenia, it can be treated with medication, therapy, and support. In this article, we will provide an overview of some current research topics in schizophrenia.

What You'll Learn

Thirty Schizophrenia Research Topics

1. The causes of schizophrenia. 2. The symptoms of schizophrenia. 3. The relationship between schizophrenia and creativity. 4. The link between schizophrenia and violence. 5. The role of genetics in schizophrenia. 6. The role of the environment in schizophrenia. 7. The prevalence of schizophrenia in different cultures. 8. The impact of schizophrenia on the family. 9. The economic cost of schizophrenia. 10. The treatment options for schizophrenia. 11. The effectiveness of medication for treating schizophrenia. 12. Alternative treatments for schizophrenia. 13..The challenges of living with schizophrenia. 14..How to cope with the symptoms of schizophrenia

15..The role of support groups in managing schizophrenia 16. The importance of early diagnosis and treatment of schizophrenia 17. The long-term outlook for people with schizophrenia 18. The impact of schizophrenia on employment 19. The effect of schizophrenia on relationships 20. Having a baby when you have schizophrenia21. Parenting with schizophrenia 22. Schizophrenia and substance abuse 23. Schizophrenia and self-harm 24. Schizophrenia and suicide 25. The role of the media in reporting on schizophrenia 26. The use of service user involvement in mental health research 27. The experiences of people from black and minority ethnic groups with schizophrenia 28. The experiences of carers of people with schizophrenia 29. Improving access to services for people with schizophrenia 30. Developing new treatments for schizophrenia

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105 Schizophrenia Research Topics & Essay Examples

📝 schizophrenia research papers examples, 🏆 best schizophrenia essay titles, 🎓 simple research topics about schizophrenia, ❓ schizophrenia research questions, 📣 schizophrenia discussion questions.

Clozapine Treatment for Paranoid Schizophrenia Clozapine would be an effective choice for Caitlyn since this medication is prescribed for individuals suffering from severe forms of schizophrenia.
Adult Psychiatry: Schizophrenia in Quadruplets Four Genain quadruplets developed schizophrenia, but the course of the disease was different for each of them.
Geriatric Mental Health: Dementia & Schizophrenia This paper reviews the case study of a 67-year-old patient admitted to a hospital with agitation, hallucinations, and paranoia after a medication course.
Different Methods of Treating Schizophrenia Schizophrenia is a disorder that disables the brain in a severe and chronic manner. This paper examine the different treatments of Schizophrenia and their effectiveness and side effects.
Schizophrenia: Cause, Consequence, Care Being one of the most widespread mental disorders in terms of identifying major symptoms, schizophrenia still remains quite complicated when it comes to the etiology examination.
Positive and Negative Symptoms of Schizophrenia
Dysregulated but Not Decreased Salience Network Activity in Schizophrenia
Treatment Intervention for Paranoid Schizophrenia
Biological and Cognitive Approaches for the Treatment of Schizophrenia
Schizophrenia and Its Effects on the Way People Interpret
Schizophrenia and Cortical Blindness: Protective Effects and Implications for Language
Treatment-Resistant Schizophrenia: Genetic and Neuroimaging Correlates
Definitions and Social Perceptions of Schizophrenia
Hippocampus and Schizophrenia Causes
Disorganized Schizophrenia and Its Effects on Children
Disorganized Schizophrenia and Methodist Unity Point
Schizophrenia, Substance Abuse, and Violent Crime
Functional Connectivity Density Alterations in Schizophrenia
Schizophrenia and Its Effects on Young Children and Adolescents
Hispanic and Urban Black Populations and Schizophrenia
Attention and Multisensory Integration of Emotions in Schizophrenia
Negative Symptoms and Hypofrontality in Chronic Schizophrenia
Resilience and Cognitive Function in Patients With Schizophrenia and Bipolar Disorder, and Healthy Controls
Schizophrenia and Family Interventions
Schizophrenia and Anti-Social Personality Disorder
White Matter Measures and Cognition in Schizophrenia
Clinical Practice on Schizophrenia Family Work
Neurocognitive Decrements Are Present in Intellectually Superior Schizophrenia
Altered Cerebral Blood Flow Covariance Network in Schizophrenia
Schizophrenia and Its Effects on the Development of Schizophrenia
Dopamine, Psychosis and Schizophrenia: The Widening Gap Between Basic and Clinical Neuroscience
Psychosocial Rehabilitation for Schizophrenia
Psychology: Schizophrenia and Widely Used Treatments
Chronicity and Sex Affect Genetic Risk Prediction in Schizophrenia
Paranoid Schizophrenia and Nursing Interventions
Perinatal Factors and Schizophrenia
Altered Basal Ganglia Network Integration in Schizophrenia
Schizophrenia Stigmas, Causes, and Brain Activity Differences
Antipsychotics, Metabolic Adverse Effects, and Cognitive Function in Schizophrenia
Schizoaffective Disorder: The Bridge Between Schizophrenia and Bipolar
Dysfunctional Brain Networks and Genetic Risk for Schizophrenia
Demystifying Common Misconceptions About Schizophrenia
Schizophrenia and Emergency Room Costs
Schizophrenia and Causes for This Complex and Puzzling Illness
Antigliadin Antibodies Relation to Neurochemistry in Schizophrenia
How Do Gray Matter Effects Schizophrenia and Bipolar Disorder?
What Is the Role of Brexpiprazole in the Management of Schizophrenia?
Can Exercise Increase Fitness and Reduce Weight in Patients With Schizophrenia and Depression?
How Is Near Cognitive Correction for Schizophrenia Performed?
How Does Smoking Affect Schizophrenia?
How Can Nurses Deal With a Patient With Paranoid Schizophrenia?
Are People With Schizophrenia Dangerous and Unpredictable?
Are Patients With Schizophrenia Impaired in Processing Non-emotional Features of Human Faces?
What Is the Relationship Between Schizophrenia and Crime?
Schizophrenia and Medication Adherence and Health Care?
Is Early Intervention Occupational Therapy Effective for Schizophrenia?
How Will the Mild Encephalitis Hypothesis of Schizophrenia Influence Stigmatization?
What Are the Major Main Barriers to Treatment That Someone With Schizophrenia?
How Do Environmental Factors Affect the Development of Schizophrenia?
How To Reduce Social Interaction Anxiety in Schizophrenia?
What Are the Environmental and Genetic Effects of Schizophrenia?
What Is the Diagnosis of the Etiology of Schizophrenia?
What Is the Relationship Between Violence and Schizophrenia?
Biological and Environmental Factors for Schizophrenia?
What Are the Current Controversies in the Treatment of Schizophrenia?
Non-pharmacological Interventions for Schizophrenia: How Much Can Be Achieved and How?
How Is Schizophrenia Imaging With Voxel-based Morphometry?
What Are the Genetic Risk Factors for Schizophrenia?
Subjective and Objective Cognitive Dysfunction in Schizophrenia Is There a Link?
What Is the Modified Volume and Functional Connectivity of the Habenula in Schizophrenia?
What Are False Memories of Affective Information in Schizophrenia?
How Schizophrenia Affects the Lifespan?
What Mechanism Underlies Schizophrenia?
Are Bipolar Disorder and Schizophrenia Neuroanatomically Distinct?
Does Non-adherence Increase Treatment Costs in Schizophrenia?
Why Is Schizophrenia Considered a Complex and Multifaceted Disorder?
How Do Genetic Factors Contribute to the Risk of Developing Schizophrenia?
What Are the Subtypes of Schizophrenia?
Are There Gender Differences in the Prevalence and Manifestation of Schizophrenia?
At What Age Do the Symptoms of Schizophrenia Appear?
What Are the Primary Positive Symptoms of Schizophrenia, and How Do They Manifest?
How Is Schizophrenia Diagnosed and Treated?
Why Is the Age of Onset of Schizophrenia an Important Factor in Understanding Its Course?
Can Electrical Stimulation Improve Cognition in People Living with Schizophrenia?
Is It Possible to Prevent Schizophrenia?
What Is the Relationship Between Substance Abuse and the Development of Schizophrenia?
Can Schizophrenia Be Caused by Trauma?
What Challenges Do Clinicians Face in Diagnosing Schizophrenia Accurately?
What Therapy Is Best for Schizophrenia?
Does Schizophrenia Get Worse with Age?
What Role Do Psychosocial Interventions Play in the Overall Treatment of Schizophrenia?
Can Schizophrenia Be Treated Without Medication?
Are Antipsychotic Medications Effective in Addressing the Symptoms of Schizophrenia?
Can Schizophrenia Cause Memory Loss?
How Does Schizophrenia Impact Family Dynamics and Relationships?
Can a Blood Test Detect Schizophrenia?
What Ethical Considerations Arise in the Treatment of Individuals with Schizophrenia?
Can Brain Surgery Cure Schizophrenia?
How Do Cultural Factors Influence the Experience and Perception of Schizophrenia?
Does Schizophrenia Cause Brain Damage?
Is There a Correlation Between Schizophrenia and Violent Behavior?
Why Is Schizophrenia More Common in Males?
How Does Schizophrenia Impact Employment and an Individual’s Ability to Maintain Work?
What Is the Latest Treatment for Schizophrenia?
Why Are Peer Support Programs Valuable for Individuals Living With Schizophrenia?

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90 Schizophrenia Essay Topics

🏆 best essay topics on schizophrenia, 🔎 easy schizophrenia research paper topics, 👍 good schizophrenia research topics & essay examples, 🎓 most interesting schizophrenia research titles, 💡 simple schizophrenia essay ideas.

Nash’s Schizophrenia in “A Beautiful Mind” Film
Schizophrenia in “A Beautiful Mind” Film by Howard
Schizophrenia of John Nash in “A Beautiful Mind”
A Mental Health Nursing Social Interventions for Patients With Schizophrenia
Deleuze’s “A Thousand Plateaus” and Guattari’s “Capitalism and Schizophrenia”
Schizophrenia: Definition and Symptomps
Gerontology Nursing: Schizophrenia
Factors That Caused Schizophrenia Schizophrenia is a common mental disorder among the young males and females, therefore, the paper finds out the various effects of disorder on the young adults.
Schizophrenia: A Comprehensive Explanation Schizophrenia is a severe concern of the modern health care system because it is highly complicated and associated with mental and physical health and reduced life expectancy.
Neuroscience of Schizophrenia: The Thinking Patterns The journey to understanding the neuroscience of schizophrenia continues, and firsthand stories like that of John Nash and Lewis continue to play a central role in this process.
The Portrayal of Schizophrenia in a Beautiful Mind A Beautiful Mind by Ron Howard managed to portray the schizophrenia diagnosis accurately but not without a shred of Hollywood exaggeration.
Influence of Sexual Dysfunction and Schizophrenia on Human The paper examines the causes, problems and manifestations of mental problems that affect the physical condition of a person.
Schizophrenia Treatment: Biopsychological Approaches This paper is aimed at discussing schizophrenia as a mental illness from the perspective of various biopsychological approaches.
Schizophrenia: Chapters 15-16 of Psychology by Spielman et al. This research will focus on schizophrenia, a psychological disorder discussed in chapters 15 and 16 of the book Psychology by Spielman, Jenkins, and Lovett.
Advancements in Schizophrenia Research The article’s primary goal is to review the dopamine hypothesis and study and analyze new targets invented in recent years.
A Cognitive-Behavioural Therapy Utility of Schizophrenia The paper describes how cognitive-behavioral therapies may be utilized in mental health settings to aid schizophrenic patients in overcoming mental health problems.
Consciousness and Psychedelic Sciences in Managing Schizophrenia Behavioral management is emerging as a significant intervention in psychiatric treatment, focusing mainly on preserving order for those with clinical mental illness.
Gender Differences in Schizophrenia The study sheds light on the gender differences in schizophrenia onset. Schizophrenia in women and men manifests itself at different ages.
Schizophrenia Disorder Diagnosis The main reason for the patient’s visit entails experiences and behavior out of touch with reality. It is the duty of a practitioner to enhance optimal Medicare for a patient.
Schizophrenia Diagnosis, Treatment, and Prognosis This study evaluates the diagnosis of schizophrenia in a high school teenager, focusing on their background history to assert the prevalence of a different disorder.
Variables Impacting a Patient With Schizophrenia The mother brought Demetri, her 39-year-old son previously diagnosed with schizophrenia, because of his deteriorating mental well-being.
Medical Terminology of Treating Schizophrenia The article Clinical relevance of paliperidone palmitate 3-monthly in treating schizophrenia discusses how the mentioned injectable antipsychotic (PP3M) improves non-adherence.
Gender Differences in Development of Schizophrenia Schizophrenia has varied effects on men’s and women’s sexual life. These effects could be due to variances in the start of schizophrenia at different ages.
Aspects of Schizophrenia Schizophrenia is a severe mental disorder that demands a specific response. It is vital to diagnose it by using available criteria.
Schizophrenia in Young Women and Men Schizophrenia, according to several researches, affects both men and women. However, men show high vulnerability as the development of this disorder is concerned.
Schizophrenia Treatment With Fluphenazine Decanoate The present paper suggests Fluphenazine Decanoate as a medicine useful for decreasing the patient’s paranoid behavior.
Case Presentation: Schizophrenia The client’s name for this case presentation is Clara Hunters. She is a thirty-three-year-old woman. She is white and has been married for five years.
Schizophrenia: Fundamentals and Possible Causes The medicinal approach involves taking drugs based on histone deacetylases, as they improve the condition of certain parts of histones’ acetylation.
Evaluation of the Symptoms of Schizophrenia in “A Beautiful Mind” In this study, the “Diagnostic and Statistical Manual of Mental Disorder” was used to evaluate the symptoms of the main character of the movie called “A Beautiful Mind”.
Schizophrenia: Diagnosis and Treatment The presence of signs such as hallucinations, delusions, cognitive issues, and negative symptoms is a marker of developing schizophrenia.
Schizophrenia: Myths, Causes, and Impacts Schizophrenia is a major mental condition characterized by a combination of unusual behaviors such as hallucinations, delusion, and abnormal thinking.
Schizophrenia. Abnormal Psychology The implications of the analysis include the unmet need for schizophrenia stigma reduction strategies for both general audiences and mental health communities.
Schizophrenia: Causes and Symptoms The leading causes of the development of schizophrenia include heredity, an unfavorable environment, and negative social conditions.
Schizophrenia and Dopamine Level It is essential to examine the role of dopamine to understand whether the level of this neurotransmitter is high or low in schizophrenia.
Case Study of Schizophrenia: Symptoms, Misconceptions and Diagnosis The case study describes the appointment with Jasmine Mack, an African American 18-years old college student who has experienced several symptoms associated with schizophrenia.
Schizophrenia Depicted in “A Beautiful Mind” Film Schizophrenia affects millions of people worldwide, and one of them is John Nash, a mathematician played by Russell Crowe in the film “A Beautiful Mind” by Ron Howard.
Schizophrenia: Diagnosis, Prevention, and Treatment Articles included in the annotated bibliography describe the causes, diagnosis, prevention, and treatment of schizophrenia.
Schizophrenia Symptoms and Diagnosis: Patient Interview This article proposes an interview with a patient with schizophrenia, gives his reactions to the questions of the interviewer and describes the symptoms of the disease.
Biological Strategies for Studying Schizophrenia This paper analyzes several major current approaches to studying schizophrenia. It specifically focuses on several streams of research.
Schizophrenia as Dangerous Mental Disease Schizophrenia is a very dangerous mental disease, which affects a human mind in numerous ways. It warps a person’s perception of reality.
Schizophrenia as the Most Challenging Psychological Disorder Despite its relatively low prevalence, schizophrenia ranks among the most impairing and debilitating psychological conditions in people
Features of Schizophrenia as Neurodegenerative Disorder This paper describes schizophrenia as a neurodegenerative disorder and tries to understand the key underlying elements linked with the clinical aspect of schizophrenia.
Schizophrenia Treatment With Approved Drug Schizophrenia is one of the most common mental disorders in the US. Treatment of schizophrenia is critical since patients stand as dangers to themselves and society.
Schizophrenia and Folate Status Correlation The research is designed to clarify the relationship between folate status and schizophrenia with an effort to avoid methodological pitfalls during the investigation.
The Concept of Symptoms in Schizophrenia The essay will delve into the concept of symptoms in schizophrenia and underline the implications for the patient’s treatment.
Drugs for Treating Schizophrenia and Mood Disorders Schizophrenia and mood disorders are serious mental illnesses, which are challenging to treat. Millions of people suffer from adverse effects on all aspects of life.
Schizophrenia Versus Schizoaffective Disorders Schizophrenia and schizoaffective are two distinct disorders, each having its way of diagnosis and treatment. However, they share almost similar psychotic characteristics.
Schizophrenia: Causes, Symptoms, Treatments, and Myths This paper will discuss the causes and symptoms of schizophrenia, the ways of its treatment, and the myths that surround this mental illness.
Connection Between Schizophrenia and Neurotransmitters Neurotransmitters do the visible impact on the development of schizophrenia, although it manifests when they are inflamed.
Schizophrenia Disorder: Causes and Treatment Schizophrenia is a mental disease, which affects the thinking capacity of an individual. A considerable number of populations around the globe are affected by this disease.
An Accurate Portrayal of Schizophrenia This paper will analyze the Schizophrenia along with its symptoms. It will also analyze an important scene in the movie “a beautiful mind” which was directed by Ron Howard.
Schizophrenia: Non- and Pharmacological Treatment There are effective pharmacological approaches to treating Schizophrenia, such as Clozapine, and non-medical methods, such as psychoeducation.
Understanding Mental Illness: Aspects of Schizophrenia There is a significant social stigma surrounding severe mental illness such as schizophrenia which leads to discrimination of not just the patient, but the whole family.
Family Psychoeducation for Schizophrenia Patients This work reviews a meta-analysis on FPE conducted, focusing on the effectiveness of the educational approach in treating patients with schizophrenia and supporting their families.
Schizophrenia in a First-Year College Student The paper studies a case of schizophrenia, which manifested in a 39-year-old woman during her first year at college in the form of prodromal symptoms, which caused her to drop out.
Schizophrenia Features Among African American Men Schizophrenia is a serious mental disorder that may occur at any age. African Americans usually have severe psychotic symptoms regarding the scope and quality of hallucinations.
Schizophrenia and QT Prolongation The paper considers the case of a 62-year-old woman with a history of psychiatric diagnoses, which indicates her predisposition to delusions.
Schizophrenia: Approaches and Behavior It is hypothesized the symptoms of schizophrenia can be attributed to the increased dopaminergic activities in such brain areas as striatum and thalamus.
Schizophrenia: Physiological Basis of a Mental Illness Schizophrenia is mental illness with a genetic basis and its complexity is presents in form of chronic psychosis and the cognitive ability of the individual becomes impaired.
Psychiatry: The Multi-Dimensional Nature of Schizophrenia Schizophrenia is a psychological condition in which patients suffer from disabling chronic mental disorders that adversely affect the normal functioning of the brain.
Difficulties That the Person With Schizophrenia Goes Through
Altered Cerebral Blood Flow Covariance Network in Schizophrenia
Broader Visual Orientation Tuning in Patients With Schizophrenia
Imaging Schizophrenia With Voxel-Based Morphometry
Antipsychotics, Metabolic Adverse Effects, and Cognitive Function in Schizophrenia
Chronicity and Sex Affect Genetic Risk Prediction in Schizophrenia
Correlation Between Child Abuse and Schizophrenia
Genetic and Environmental Factors of Schizophrenia
Complex Gastrointestinal and Endocrine Sources of Inflammation in Schizophrenia
Environmental and Genetic Effects and Schizophrenia
Current Controversial Issues During Treatment of Schizophrenia
Environmental Factors and the Development of Schizophrenia
Cognitive Behavioral Therapy for Schizophrenia
Biological and Cognitive Approaches for the Treatment of Schizophrenia
Antigliadin Antibodies Relation to Neurochemistry in Schizophrenia
Considering Brexpiprazole and Its Role in Managing Schizophrenia
Disrupted Thalamic Resting-State Functional Networks in Schizophrenia
Demystifying Common Misconceptions About Schizophrenia
Implementing Evidence-Based Practice With Schizophrenia
Altered Volume and Functional Connectivity of the Habenula in Schizophrenia
Causes and Key Symptoms of Paranoid Schizophrenia
Definitions and Social Perceptions of Schizophrenia
Decreasing Social Interaction Anxiety for Schizophrenia
Identifying Modifiable Risk Factors for Relapse in Patients With Schizophrenia in China
Family Education and Management of Schizophrenia
Creativity and Schizophrenia Spectrum Disorders Across the Arts and Sciences
Diagnosing and Treating Schizophrenia
Drug Abuse and Schizophrenia
Critical Diagnostic Review of Schizophrenia
Disorganized Schizophrenia and Its Effects on Children

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These essay examples and topics on Schizophrenia were carefully selected by the StudyCorgi editorial team. They meet our highest standards in terms of grammar, punctuation, style, and fact accuracy. Please ensure you properly reference the materials if you’re using them to write your assignment.

This essay topic collection was updated on January 9, 2024 .

Everything begins with an idea!

Schizophrenia Research Paper Topics

Schizophrenia is a chronic mental disorder that affects how a person thinks, expresses emotions, acts, and perceives reality. Schizophrenia is among the most complex mental disorder. Due to its complex nature, students have a high chance of struggling with schizophrenia research paper topics. As a student, you should realize that a schizophrenia research paper is quite easy to write if you get a good topic to use. We know that many students don’t have enough time to be brainstorming for topics, which is why we decided to help them with topic ideas. We have listed the best schizophrenia research paper topics below. The topics that we listed below will assist you in making the most out of your research paper. You’ll quickly know what to write about any topic that you choose here after you carry out a little research. We implore you to make attempts to meet some patients with this mental disorder and use your findings in your research paper. By using the topics here for your research paper, you will surely surprise your professors and colleagues. More importantly, these topics will assist you in comprehending the medical issue of schizophrenia fully.

A Report On Schizophrenia
Association between Intracellular Pathogens and Schizophrenia
Diagnosis Of Schizophrenia
Genetic Links Between Associated Co-morbid Conditions and Schizophrenia
Schizophrenic Bipolar And Schizophrenia
Is Schizophrenia A Mental Disorder?
Living With Schizophrenia
The Dangers Of Having Schizophrenia
Causes Of Schizophrenia
Treatment Of Schizophrenia
The similarity between bipolar disorder and schizophrenia
Description Of Catatonic Schizophrenia
Analysis of Catatonic Schizophrenia
Childhood-Onset Schizophrenia
Is Schizophrenia An Incurable Mental Illness?
New Treatments for Schizophrenia
Trial Treatments for Schizophrenia
The Effect Of Medical Marijuana On Individuals with Schizophrenia
Schizophrenia Among Healthcare Professionals
Mental Health Condition Of Schizophrenia
How Do Genetic Factors Contribute To The Development Of Schizophrenia?
Behavioral Aetiology Of Schizophrenia
Schizophrenia and Neuroplasticity
Schizophrenia As A Serious Disorder
A Person With Schizophrenia
Schizophrenia and Homelessness
Schizophrenia and Aging
Psychotherapy For Treating Schizophrenia
Schizophrenia – Longitudinal Studies
Schizophrenia As A Psychotic Disorder
Schizophrenia and PET Scan Findings
Symptoms Of Schizophrenia
Early Signs Of Schizophrenia
How Schizophrenia Affects Cognitive Ability
How Schizophrenia Develops
Symptoms And Treatment Of Schizophrenia
Correlation Between Schizophrenia And Poverty
Disorder of Lifespan Development And Schizophrenia
The Effects Of Schizophrenia On Children
The Effects Of Schizophrenia On Adults
Is Any Particular Race More Vulnerable To Schizophrenia?
Schizophrenia And Other Psychotic Disorders
The Development Of Schizophrenia
Schizophrenia Of Children And Adolescents
The Pathogenesis of Schizophrenia
How The ‘Glutamate Theory’ Is Related To Schizophrenia
The Mental Health Consumer Movement And Schizophrenia
A Detailed Description Of A Schizophrenic Mind
How Schizophrenia Affects Brain Development In Children With Schizophrenia
The Diagnostic Criteria Of Schizophrenia
How Does Schizophrenia Affect People Who Live In States That Opted Out Of The State Healthcare Exchanges?
The Enigma of Schizophrenia
The Connection Between Violence And Schizophrenia
The Mental Illness Of Schizophrenia
What is Schizophrenia?
The Mental Condition Of Schizophrenia
The Vicious Cycle Of Schizophrenia
Treatment Of People With Schizophrenia
The History of Schizophrenia
The Possible Future Of Schizophrenia
Ia Schizophrenia A Genetically Transmittable Illness?
Development Of Schizophrenia
Why The Reality Of Schizophrenia Frightens Many American Citizens
Medical Solution To Schizophrenia
How To Prevent The Development Of Schizophrenia In Children
Are There Effective Drugs Against Schizophrenia?
Therapy For Schizophrenia
Schizophrenia And Cognitive Ability
Non-Genetic Factors That Can Cause Schizophrenia
What Is The Relationship Between Unhealthy Diet And Schizophrenia?
How To Reverse The Negative Impacts Of Schizophrenia
How Do People With Schizophrenia Perceive Their Environment?
Schizophrenia And Co-morbid Conditions
Reversible Damages That Schizophrenia Can Cause
Irreversible Damages That Schizophrenia Can Cause
What Are The Dangers Associated With Late Treatment Of Schizophrenia?
How Schizophrenia Affects Mental Health
Can Schizophrenia Cause The Death Of Brain Cells?
The Relationship Between Schizophrenia And Loss Of Memory
How Schizophrenia Affects Consciousness
Can Schizophrenia Affect Neurons?
How Schizophrenia Changes Brain Function
What Makes A Person Vulnerable To Schizophrenia?
How Schizophrenia Retards Brain Performance
The Health Risks Associated With Schizophrenia
What It Take To Treat Schizophrenia
The Side Effects Of Schizophrenia Treatment On Patients
The Dangers Of Living With Schizophrenia
How Can Schizophrenia Reflect On The Physical Health?
How Schizophrenia Affects Women

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Schizophrenia research papers: tips and topics.

Schizophrenia is regarded as one of the most serious psychiatric disorders that exist. It is also one of the most common psychiatric disorders. Symptoms of the disease include disorganized speech behavior, hallucinations, and delusional thoughts. Schizophrenia research as with other research under psychiatric medicine areas of today is tailored towards the industry demand.

Over the years, there has been a massive increase in educational programs, however with little or no increase in schizophrenia research topics. As a result, current research on schizophrenia deals more with the prescribing of newer antipsychotic agents. The implication is that there is a vast array of grey in schizophrenia studies. This article will provide some tips that you might need to write schizophrenia research papers on your own, and to standard.

Writing a Good Research Paper on Schizophrenia

In writing a good schizophrenia paper, here are some steps that you can follow, that would be very helpful.

In some cases, you might be lucky enough to be assigned a topic that makes this step relatively irrelevant. Otherwise, if you are to choose a topic on your own, of all the steps involved in writing your research paper on schizophrenia, this might be the toughest. First, you would have to research schizophrenia to understand what you are going into. After this, you would have to decide if your schizophrenia paper would be on areas of research that have previously been touched. You could also decide to dive into totally new research on schizophrenia.

Whichever topic you choose, a good research topic should not be too broad. A relatively broad topic might capture a general view of the research rather than capture a more specific view. For instance, a topic like “Hard drug dependence in Schizophrenia” can easily be narrowed down to “Nicotine dependence in Schizophrenia patients.”

After you might have selected an article that suits you, the next phase is proper research on your chosen topic. You can use the internet to get yourself a lot of schizophrenia research articles. In achieving this aim, you can make good use of Google Scholar.

A simple search with the words “latest research on schizophrenia” or “new research on schizophrenia” would bring you journals that might be helpful in your research study. After you might have found the schizophrenia research article that you need, do well to write down your sources in a way that you can write your references properly in the end.

Developing an outline will help you come up with ideas as well as order your thoughts appropriately. Without a proper outline, your work might like focus and direction. In creating your schizophrenia research paper outline, you create subheadings that have central themes with the topic you have chosen.

Look at these subheadings as key points that you need to discuss your topic for proper understanding. You’ll need to develop the points using what you have found in your schizophrenia research and in the research articles on schizophrenia that you have read.

In writing your research paper on schizophrenia, you could go through two ways. You could start typing your work directly or you could first have a draft. Having a draft will allow you to create a more error-free schizophrenia research paper. However, making a draft could see you extend the time you have in coming up with your schizophrenia paper.

Schizophrenia Research Journals

To come up with a research article on schizophrenia that is of standard, you’ll need to cite some journals. From these journals, you will find research papers on schizophrenia. From these papers, you’ll find the results of a series of schizophrenia research studies that might be helpful. You can also contact professional writers who are experts in this field. Here is a list of journals that are available at your disposal.

Schizophrenia Research . The schizophrenia research journal is a journal that contributes to the dissemination of information associated with research on schizophrenia. The schizophrenia research impact factor as of 2018 by Clarivative Analysis is 4.569.
Schizophrenia Bulletin . In this journal, you will find reviews on recent development in the world of research in schizophrenia. It looks into areas of schizophrenia research study bordering around the etiology and treatment of schizophrenia. The Schizophrenia bulletin impact factor is 7.289.
World Psychiatry . this journal is published by the world’s Psychiatric association. The Journal deals widely with psychiatric medicine as a whole. However, it could as well provide readers with answers to schizophrenia research questions about significant clinical, service and research developments.
Proceedings from Conferences . In addition to journals, you can make use of proceedings from conferences. For instance, proceedings from the international congress on schizophrenia research that takes place once in two years.

Sample Schizophrenia Research Paper Topics

Just in case you need a topic to write on for your research paper on Schizophrenia, here are a few topics you can work with:

The role of alkaloid in schizophrenic psychosis.
Relationship between schizophrenic psychosis and animate thing Pathogens
Medical Marijuana and its impact on people with Schizophrenia
“Schizophrenia and also the psychological state shopper Movement
Incidence of schizophrenic psychosis Among tending Professionals
Genetic Links Between schizophrenic psychosis and Associated Co-morbid Conditions”
Longitudinal Studies on Schizophrenic psychosis
Schizophrenic psychosis and Aging
New Treatments for schizophrenic psychosis presently in Clinical Trials
Schizophrenic psychosis and PET Scan Findings”
Schizophrenia, Schizophrenic psychosis and Neuroplasticity
Schizophrenia, Schizophrenic psychosis and Homelessness
The impact on people with schizophrenic psychosis in states that opted out of health care Expansion/The State tending Exchanges underneath the Affordable Care Act

Having all the necessary information relating to your topic would not necessarily make your schizophrenia research paper a good one. A good research paper in addition to having all the necessary information is one that is free of errors. Amongst other things, make sure to review your work properly for grammatical errors. Finally, look out for the flow, use of logic, sentence structure, the order of paragraphs, and avoid plagiarism.

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Schizophrenia Research Topics

Schizophrenia essay titles, schizophrenia paper topics, schizophrenia research questions.

Schizophrenia Research Topics: Schizophrenia is a complex mental disorder. When writing research topics on Schizophrenia one has to be very careful on the topics since one should be conversant with the topic. Hope the list of schizophrenia research paper topics below will give you a starting point in writing your research paper.

1. Treatment Of People With Schizophrenia

2. The Vicious Cycle Of Schizophrenia

3. The Reality Of Schizophrenia Is A Frightening Menace

4. The Progression Of Development Of Schizophrenia

5. The Mental Illness Of Schizophrenia

6. The Mental Condition Of Schizophrenia

7. The History and Future of Schizophrenia

8. The General Psychiatric Symptoms Of Schizophrenia

9. The Enigma of Schizophrenia

10. The effect on Individuals with Schizophrenia in states that opted out of Medicaid Expansion/The State Healthcare Exchanges under The Affordable Care Act

Read: Argumentative Essay Topics about Mental Health

11. The Diagnostic Criteria Of Schizophrenia

12. The Connection Between Schizophrenia And Violence

13. The Cognitive Behavioral Aetiology Of Schizophrenia

14. The ‘Glutamate Theory’ of the Pathogenesis of Schizophrenia

15. Symptoms And Treatment Of Patients With Schizophrenia

16. Symptoms And Symptoms Of Schizophrenia

17. Schizophrenia, The Schizophrenic Mind Is Not So Much Split As Shattered

18. Schizophrenia Of Children And Adolescents

19. Schizophrenia Is A Serious Disorder

Read: Research Topics on Mental Health

1. Schizophrenia As A Psychotic Disorder

2. Schizophrenia And Treatment Of Schizophrenia

3. Schizophrenia and the Mental Health Consumer Movement

4. Schizophrenia and PET Scan Findings

5. Schizophrenia And Other Psychotic Disorders

6. Schizophrenia and Neuroplasticity

7. Schizophrenia And Its Effects On The Development Of Schizophrenia

8. Schizophrenia And Its Effects On People

9. Schizophrenia And Its Effects On Children

10. Schizophrenia and Homelessness

11. Schizophrenia and Disorder of Lifespan Development

12. Schizophrenia and Aging

13. Schizophrenia – Longitudinal Studies

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14. Schizophrenia Symptoms And Treatment Of Schizophrenia

15. Schizophrenia A Correlation Between Poverty And Schizophrenia

16. Psychotherapy as a Treatment for Schizophrenia

17. New Treatments for Schizophrenia Currently in Clinical Trials

18. Mental Health Condition Of Schizophrenia

19. Living With Schizophrenia

20. Marijuana and it’s effect on Individuals with Schizophrenia

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1. Incidence of Schizophrenia Among Healthcare Professionals

2. Genetic Links Between Schizophrenia and Associated Co-morbid Conditions

3. Diagnosis Of Schizophrenia

4. Description and Analysis of Catatonic Schizophrenia

5. Childhood Onset Schizophrenia And Schizophrenia

6. Causes and Treatments of Schizophrenia

7. Bipolar Vs. Schizophrenia Bipolar And Schizophrenia

8. A Depth Report On Schizophrenia

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1. Is there an Association between Schizophrenia and Intracellular Pathogens?

2. What are the positives signs of Schizophrenia?

3. Is Schizophrenia A Psychological Or Mental Disorder?

4. How to treat Schizophrenia medically?

5. What to know about Schizophrenia?

6. Is supportive therapy effective in managing Schizophrenia

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Schizophrenia Research Paper

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Schizophrenia is a psychotic disorder characterized by disturbances in thought, emotion, and behavior. This research paper discusses the symptoms, etiology, treatment, and other pertinent issues concerning this mental illness.

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Get 10% off with 24start discount code, i. description and classification, a. symptoms, 1. delusions, 2. hallucinations, 3. disorganized speech, 4. disorganized or catatonic behavior, 5. negative symptoms, b. variability of symptoms among patients, c. subtypes of schizophrenia, ii. history, iii. demographic characteristics of schizophrenia, a. sex differences, b. social class differences, iv. life functioning and prognosis, a. long-term course, b. premorbid characteristics of schizophrenia, v. etiology: theories and research findings, a. brain abnormalities in schizophrenia, b. biochemical factors, c. genetics, d. obstetrical complications, e. viral infection, f. diathesis-stress model, vi. treatment and therapy, a. antipsychotic medication, b. psychological treatment, vii. summary.

Delusions are the primary example of abnormal thought content in schizophrenia. Delusional beliefs conflict with reality and are tenaciously held, despite evidence to the contrary. There are several types of delusions. Delusions of control is the belief that one is being manipulated by an external force, often a powerful individual or organization (e.g., the FBI) that has malevolent intent. Delusions of grancleur refers to patients’ beliefs that they are especially important and have unique qualities or powers (e.g., the capacity to influence weather conditions). In contrast, some patients express the conviction that they are victims of persecution or an organized plot, and these beliefs are referred to as delusions of persecution. Examples of more specific delusions include thought broadcasting, the patient’s belief that his or her thoughts are transmitted so that others know them, and thought withdrawal, the belief that an external force has stolen one’s thoughts.

Hallucinations are among the most subjectively distressing symptoms experienced by schizophrenia patients. These perceptual distortions vary among patients and can be auditory, visual, olfactory, gustatory, or tactile. The majority of hallucinations are auditory in nature and typically involve voices. Examples include the patient hearing someone threatening or chastising him or her, a voice repeating the patient’s own thoughts, two or more voices arguing, and voices commenting. The second most common form of hallucination is visual. Visual hallucinations often entail the perception of distortions in the physical environment, especially in the faces and bodies of other people.

Other perceptual distortions that are commonly reported by schizophrenia patients include feeling as if parts of the body are distorted in size or shape, feeling as if an object is closer or farther away than it actually is, feeling numbness, tingling, or burning, being hypersensitive to sensory stimuli, and perceiving objects as flat and colorless. In addition to these distinctive perceptual abnormalities, persons suffering from schizophrenia often report difficulties in focusing their attention or sustaining concentration on a task.

It is important to note that in order for an unsubstantiated belief or sensory experience to quality as a delusion or hallucination, the individual must experience it within a clear sensorium (e.g., unsubstantiated sensory experiences that occur only upon awaking from sleep or when falling asleep would not qualify as delusions). Thus, for example, if a patient reports hearing something that sounds like voices when alone, but adds that he or she is certain that this is a misinterpretation of a sound, such as the wind blowing leaves, this would not constitute an auditory hallucination.

The DSM uses the term disorganized speech to refer to abnormalities in the form or content of the individual’s verbalizations. It is assumed that these abnormalities reflect underlying distortions in the patient’s thought processes. Thus the term thought disorder is frequently used by researchers and practitioners to refer to the disorganized speech that often occurs in schizophrenia.

Problems in the form of speech are reflected in abnormalities in the organization and coherent expression of ideas to others. One common abnormality of form, incoherent speech, is characterized by seemingly unrelated images or fragments of thoughts that are incomprehensible to the listener. The term loose association refers to the tendency to abruptly shift to a topic that has no apparent association with the previous topic. In general, the overall content of loosely associated speech may be easier to comprehend than incoherent speech. In perseverative speech, words, ideas, or both are continuously repeated, as if the patient is unable to shift to another idea. Clang association is the utterance of rhyming words that follow each other (e.g., “a right, bright kite”). Patients choose words for their similarity in sound rather than their syntax, often producing a string of rhyming words.

The overt behavioral symptoms of schizophrenia fall in two general areas: motor functions and interpersonal behavior. Motor abnormalities, including mannerisms, stereotyped movements, and unusual posture, are common among schizophrenia patients. Other common signs include bizarre facial expressions, such as repeated grimacing or staring, and repeated peculiar gestures that often involve complex behavioral sequences. As with other symptoms of the psychosis, the manifestation of motor abnormalities varies among individuals. Schizophrenia patients sometimes mimic the behavior of others, known as echopraxia, or repeat their own movements, known as stereotyped behaviors. Although a subgroup of patients demonstrate heightened levels of activity, including motoric excitement (e.g., agitation or flailing of the limbs), others suffer from a reduction of movement. At the latter extreme, some exhibit catatonic immobility and assume unusual postures that are maintained for extended periods of time. Some may also demonstrate waxy flexibility, a condition in which patients do not resist being placed into strange positions that they then maintain. Catatonia has decreased dramatically in recent decades, so that it is now rare. Several researchers have attributed this decline to the introduction of antipsychotic medication (described later).

In the domain of interpersonal interactions, schizophrenia patients frequently demonstrate behaviors that are perceived as bizarre or inappropriate by others. For example, it is not uncommon for patients to use socially unacceptable language and unusual tones of voice, or to show overly dependent or intrusive behavior. Another common symptom, inappropriate affect, involves unusual emotional reactions to events and experiences. For example, patients may laugh at a sad or somber occasion, or be enraged by insignificant events. Finally, many patients manifest increasingly poor hygiene as their illness progresses. Their appearance may also be marked by disheveled clothing or inappropriate clothing, such as gloves and coats in the summer.

The symptoms of schizophrenia can be classified into the general categories of positive and negative. Positive symptoms involve behavioral excesses and most of the symptoms described earlier fall in to this category (e.g., delusions, hallucinations, and bizarre behaviors). In contrast, negative symptoms involve behavioral deficits. Examples include fiat affect (blunted expressions of emotion), apathy, and social withdrawal. In the domain of verbal expression, schizophrenia patients who manifest a very low rate of verbal output are described as showing poverty of speech. Patients whose speech is normal in quantity, but lacks meaning, suffer from poverty of content. Recently, some researchers have suggested that positive and negative symptoms may be caused by different neural mechanisms.

It is important to mention that a reduction in overt displays of emotion does not necessarily imply that patients have less intense subjective emotional experiences than the average person. In fact, recent findings indicate that blunted emotional expressions can coexist with intense subjective feelings of emotion.

According to DSM-IV, patients must show two or more of the preceding five symptoms to meet the diagnostic criteria for schizophrenia. Thus, no one of these symptoms is required for the diagnosis. Furthermore, the following four criteria must also be met: (1) the patient shows marked deterioration in occupational, interpersonal, or domestic functioning; (2) the patient manifests continuous signs of symptoms or dysfunction for at least 6 months; (3) the patient does not manifest predominant signs of mood disturbance (e.g., depression or mania); and (4) the symptoms are not caused by substance abuse or a primary medical condition.

Because the diagnostic criteria for schizophrenia are relatively broad, with no one essential symptom, there is a great deal of variability among patients in their symptom profiles. It has therefore been proposed that schizophrenia is a heterogeneous disorder with multiple causes. It is also the case, however, that patients must show a marked and persistent impairment to meet the diagnostic criteria for schizophrenia. Thus, those who meet criteria for the diagnosis are significantly impaired in everyday functioning. For many individuals who are diagnosed with schizophrenia, independent functioning is never achieved.

The DSM lists five subtypes of schizophrenia. In schizophrenia of the paranoid type, delusional concerns about persecution and/or preoccupation with threat dominate the clinical presentation, although delusions of grandeur are also often present. Disorganized schizophrenia is distinguished by extremely incoherent speech and behavior, as well as blunted or inappropriate affect. In catatonic schizophrenia, the clinical picture is dominated by abnormalities in movement and posture, such as those described earlier. Patients classified as having undifferentiated schizophrenia do not meet criteria for any of the previous subtypes. Finally, the diagnosis of residual schizophrenia is applied to patients who have had at least one episode of schizophrenia and who continue to show functional impairment, but who do not currently manifest any positive symptoms.

During the late 1800s and early 1900s, Emil Kraepelin and Eugen Bleuler provided the first conceptualizations of schizophrenia. Kraepelin defined “dementia praecox,” the original term for schizophrenia, as an endogenous psychosis characterized by intellectual deterioration (dementia) and early onset (praecox). Kraepelin included negativism, hallucinations, delusions, stereotyped behaviors, attentional difficulties, and emotional dysfunction as major symptoms of the disorder. Kraepelin’s work focused on description and phenomenology, leaving subsequent researchers to investigate the cause or causes of the disorder.

In contrast to Kraepelin, Eugen Bleuler, a Swiss psychiatrist, proposed a broader view of dementia praecox, with a more theoretical emphasis. Bleuler contested two of Kraepelin’s defining assumptions: specifically, that the psychosis was typically characterized by early onset and intellectual deterioration. Bleuler attempted to identify an underlying commonality among the diverse variations of what Kraepelin referred to as dementia praecox and concluded that all of the patients suffered from a “breaking of associative threads,” causing a disharmony among communicative and thought processes. He believed this abnormality accounted for the problems of thought, emotional expression, decision making, and social interaction associated with schizophrenia. Guided by the defining principle of disharmonious mental structures, Bleuler renamed the disorder “schizophrenia,” meaning “split mind.”

In the early to mid-1900s, American psychiatrists continued to use a broad definition of schizophrenia. The distinction between process and reactive schizophrenia was considered important, however, because it was assumed to distinguish between cases characterized by gradual deterioration (process) and cases that were precipitated by acute stress (reactive).

During this time, some clinicians and researchers viewed the specific diagnostic criteria for the major mental illnesses (schizophrenia, bipolar disorder, major depression) as artificial and discretionary, and used instead flexible and inconsistent standards for diagnoses. Studies that compared the rates of disorder across nations revealed that schizophrenia was diagnosed at a much higher rate in the United States than in Great Britain and some other countries. This national difference resulted from the use of broader criteria for diagnosing schizophrenia in the United States. Many patients who were diagnosed as having depression or bipolar disorder in Britain were diagnosed with schizophrenia in the United States. Because subsequent revisions in the DSM have included more restrictive criteria for schizophrenia, U.S. diagnostic rates are now comparable with other countries.

In addition to a more restrictive definition of schizophrenia, subsequent editions of the DSM have included additional diagnostic categories that contain similar symptoms. Thus the range of “schizophrenia spectrum disorders” continue to broaden with the description of variants of schizophrenia, such as schizoaffective disorder, which is characterized by a mix of affective and psychotic symptoms. The diagnostic category of schizophreniform disorder was also added. This diagnosis is given when the patient shows the typical symptoms of schizophrenia, but does not meet the criterion of 6 months of continuous illness.

Estimates of the prevalence of schizophrenia converge at around 1% of the population. Although there is evidence of cross-national differences in the rate of schizophrenia, the differences are not large (i.e., 1 to 2% difference). It is, in fact, striking that the rate of occurrence is so consistent across cultures.

The modal age at onset of schizophrenia is in early adulthood, usually before 25 years of age. Thus most patients have not had the opportunity to marry or establish a stable work history before the onset of the illness. As a result of this, and the often chronic nature of the illness, many patients never attain financial independence. It is relatively rare for preadolescent children to receive a diagnosis of schizophrenia. Similarly, it is rare for individuals beyond the age of 40 to experience a first episode of the illness.

Although it has traditionally been assumed that there is no sex difference in the rates of schizophrenia, some recent research findings indicate that a somewhat larger proportion of males than females meet the DSM-IV criteria for the disorder. Nonetheless, the overall rates do not differ dramatically for men and women. It is well established, however, that women are more likely to have a later onset of illness, as well as a better prognosis. Women also show a higher level of interpersonal and occupational functioning during the period prior to illness onset. The reasons for this sex difference are not known, but it has been proposed by several theorists that the female sex hormone, estrogen, may function in attenuating the severity of the illness.

Compared with the general population averages, schizophrenia patients tend to have significantly lower incomes and educational levels. Poor urban inner city districts, inhabited by the lowest socioeconomic class, contain the largest proportion of schizophrenia patients. There is a sharp contrast between the rates of schizophrenia in the lowest socioeconomic class and all other levels, including the next higher level. Findings from various cultures suggest that rates of schizophrenia are almost two times higher in the lowest social class group compared with the next lowest.

These social class differences appear to be a partial consequence of the debilitating nature of the illness. The social-drift theory suggests that during the development of schizophrenia, people drift into poverty. When the incomes and educational levels of the parents of patients are compared with those of the general population, the differences are not as striking.

There is, nonetheless, evidence that patients do come from families where the incomes and educational backgrounds of the parents are slightly below the average. These findings have led researchers to conclude that there may be a causal link between social class and risk for the illness. The sociogenic hypothesis posits that situational factors associated with low social class, such as degrading treatment from society, low levels of education, and few opportunities for achievement and reward, produce stress that contributes to the risk for schizophrenia.

Before the introduction of antipsychotic medications in 1950, the majority of patients spent most of their lives in institutional settings. There was little in the way of programs for rehabilitation. But contemporary, multifaceted treatment approaches have made it possible for most patients to live in community settings.

Of course, during active episodes of the illness, schizophrenia patients are usually seriously functionally impaired. They are typically unable to work or maintain a social network, and often require hospitalization. Even when in remission, some patients find it challenging to hold a job or to be self-sufficient. This is partially due to residual symptoms, as well as to the interruptions in educational attainment and occupational progress that result from the illness. However, there are many patients who are able to lead productive lives, hold stable jobs, and raise families. With the development of greater community awareness of mental illness, some of the stigma that kept patients from pursuing work or an education has diminished.

For about one third of patients, the illness is chronic and is characterized by episodes of severe symptoms with intermittent periods when the symptoms subside but do not disappear. For others, there are multiple episodes with periods of substantial symptom remission. About one third of those who receive the diagnosis eventually show a partial or complete recovery after one or two episodes.

Several factors have been linked with a more favorable prognosis for schizophrenia. Early treatment seems to be important in that the shorter the period between the onset of the patient’s symptoms and the first prescribed medication, the better the clinical outcome. Another indicator of better prognosis is a high level of occupational and interpersonal functioning in the premorbid period. Also, as noted earlier, women and patients who have a later onset of symptoms have a better long-term outcome.

Some of the difficulties experienced by individuals with schizophrenia can be observed before the onset of the clinical symptoms. Deficits in social skills, concentration, emotional expression, motivation, and occupational or academic performance often precede the first clinical symptoms. This period of gradual decline in functioning before the first illness episode is referred to as the prodromal phase.

However, there are often more subtle signs of dysfunction long before the onset of the prodromal period. Controlled studies using archival data sources, such as medical and school records or childhood home-movies, indicate that subtle differences are discernible as early as infancy in some patients. Individuals who succumb to schizophrenia in adulthood sometimes have abnormal motor development and show deficits in emotional expression and interpersonal relationships in early childhood. Cognitive impairment and difficult temperament have also been observed. During middle childhood and adolescence, researchers have found evidence of neurological abnormality, poor emotional control, social immaturity, and academic performance deficits. Premorbid behavioral problems often become marked through the adolescent years, and many exhibit behavioral disturbances and cognitive abnormalities that resemble the clinical symptoms of schizophrenia.

The causes of schizophrenia are unknown, but it is now widely accepted by both researchers and clinicians that schizophrenia is biologically determined. This is in striking contrast to the early and mid-1900s, when many subscribed to the theory that faulty parenting, especially cold and rejecting mothers, caused schizophrenia in offspring.

There are several sources of evidence for the assumption that schizophrenia involves an abnormality in brain function. First, studies of schizophrenia patients have revealed a variety of behavioral signs of central nervous system impairment, including motor and cognitive dysfunctions. Second, when the brains of patients are examined with in vivo imaging techniques, such as magnetic resonance imaging (MRI), many show abnormalities in brain structure. Similarly, postmortem studies of brain tissue have revealed irregularities in nerve cell formation and interconnections.

Laboratory studies of schizophrenia patients have revealed a variety of abnormalities, including irregularities in smooth pursuit eye movements, psychophysiological responses to sensory stimuli, and concentration. Research on the neuropsychological performance of schizophrenia patients was first conducted in the 1950s and continues to the present time. Individual neuropsychological tests are designed to measure functions subserved by specific regions or systems of the brain. An early finding in this area was that schizophrenia patients were the one psychiatric group whose performance on neuropsychological tests was indistinguishable from people with known brain damage. The findings suggested a generalized cerebral dysfunction in schizophrenia. However, patients show the most consistent deficits on tests of attention and memory, indicating dysfunction of the frontal and temporal lobes and the hippocampus. Further evidence of dysfunction in these brain regions is derived from poor performance on tests of executive functions: the ability to formulate, maintain, and adapt appropriate responses to the environment.

Brain-imaging studies of schizophrenia have yielded results that mirror those obtained from neuropsychological research. Some relatively consistent findings are that the brains of schizophrenia patients have abnormal frontal lobes and enlarged ventricles. Enlarged ventricles suggest decreased brain mass, particularly in the limbic regions, which are intimately involved in emotional processing. Furthermore, ventricular size correlates with negative symptoms, performance deficits on neuropsychological tests, poor response to medication, and poor premorbid adjustment. These associations between ventricular enlargement and both premorbid and postmorbid characteristics suggest that the brain abnormalities are long-standing, perhaps congenital.

In addition to brain structure, investigators have examined biological indices of brain function in schizophrenia. Functional brain-imaging studies, with procedures such as positron emission tomography (PET) and measurement of regional cerebral blood flow, reveal that schizophrenia patients have decreased levels of blood flow to the frontal lobes, especially while performing cognitive tasks.

Researchers are now pursuing the question of what causes the brain abnormalities observed in schizophrenia. Although as yet there are no definitive answers, investigators have made continuous progress in identifying factors that are associated with risk for the disorder.

The structural brain abnormalities that have been observed in schizophrenia support the assumption that it is a disorder of the central nervous system. But it has also been shown that similar structural abnormalities (i.e., ventricular enlargement and volume reductions) are present in other disorders, both neurological and psychiatric. It is therefore assumed that specific abnormalities in brain biochemistry may play a role in schizophrenia.

The functioning of the central nervous system is dependent on a host of chemicals that serve as the “messenger substances” among neurons. These chemicals or neurotransmitters have been the subject of intense investigation. Among the various neurotransmitters that have been implicated in the neuropathophysiology of schizophrenia is dopamine. Dopamine is viewed as a likely candidate for two main reasons: (1) drugs that act to enhance the release or activity of dopamine can produce psychotic symptoms, and (2) drugs that have been established to have antipsychotic properties (i.e., reduce psychotic symptoms) reduce the activity of dopamine in the brain. Current theories of the role of dopamine in schizophrenia have focused on dopamine receptors. There is evidence that there may be an abnormality in the number or sensitivity of certain dopamine receptors in the brains of schizophrenia patients. To date, however, this evidence remains inconclusive.

Several other neurotransmitters have also been hypothesized to play a role in schizophrenia. Current theories under investigation include a malfunction of the receptors for a neurotransmitter called glutamate and an abnormality in the balance between dopamine and serotonin (another neurotransmitter which, like dopamine, has been implicated in the pathogenesis of schizophrenia). As research findings on the biochemical aspects of schizophrenia accumulate, it increasingly appears that the illness may involve multiple neurotransmitters, with different biochemical profiles for different patients.

A convincing body of research supports the notion of a genetic predisposition to schizophrenia. Behavioral genetic studies of families, twins, and adopted offspring of schizophrenia patients indicate that an inherited vulnerability is involved in at least some cases of the disorder.

There is an elevated risk of schizophrenia for individuals with a biological relative who suffers from the disorder, and the risk rates increase as a function of the genetic closeness of the relationship. For example, it has been estimated that children of schizophrenia patients have a 9 to 15 % likelihood of developing the illness, siblings of patients have an 8 to 14% likelihood, and cousins have a 2 to 6% likelihood of being diagnosed with schizophrenia. Given the general population rate of approximately 1%, relatives of patients are at statistically increased risk. It must be noted, however, that relatives share common experiences as well as common genes. Therefore, examinations of the prevalence of schizophrenia in the relatives of patients cannot elucidate the relative contributions of environmental and genetic factors.

Some investigators have studied the development of adopted children whose biological mothers had schizophrenia. This approach has the potential to provide more conclusive information than family studies. The results of these investigations show that when biological offspring of schizophrenic mothers are reared from infancy in adoptive homes they are more likely to develop schizophrenia than are adopted children from healthy mothers. Furthermore, these children also exhibit a higher rate of other adjustment problems when compared with controls. Studies of this type have clearly illustrated that vulnerability to schizophrenia can be inherited.

Research on twins examines differences in concordance rates between identical (monozygotic or MZ) and fraternal (dizygotic or DZ) twins. Twin studies rely on the fact that MZ twins essentially share 100% of their genes. Thus, environmental influences account for any behavioral differences between MZ twins. In contrast, DZ twins are no more genetically similar than regular siblings; DZ twins do, however, share more similar environmental factors than do nontwin siblings. To date, the results of twin studies have consistently shown that MZ twins are significantly more likely to be concordant for schizophrenia than are DZ twins.

At the same time, it is important to note that in at least 50% of the cases in which one member of an MZ twin pair has schizophrenia, the other does not. Such “discordant” pairs have been the subject of a recent, comprehensive investigation in the United States. Among the most important findings from this research project are those from the MRI scans conducted on the twins. The ill twins in the pairs showed significantly more brain abnormalities than the healthy twins. Most notable were reductions in the volume of certain brain regions, especially the hippocampus, and increases in the size of the ventricles. These results clearly indicate the importance of environmental factors in the etiology of schizophrenia.

As is the case with many other disorders that involve brain dysfunction, there is evidence that schizophrenia is associated with exposure to prenatal and delivery complications. Obstetrical complications (OCs) are defined as physical deviations from the normal course of events during pregnancy, labor, or the neonatal period. Estimates of OCs in schizophrenics have been as high as 67%, significantly higher than the rate of OCs found in normal controls.

Among the prenatal factors that have been found to be associated with increased risk for schizophrenia are prenatal maternal nutritional deficiency, viral infection, bleeding, and toxemia. Complications of delivery that can result in hypoxia have also been linked with heightened risk for the disorder. Hypoxia, a deficiency in the amount of oxygen available to the fetus, can affect the development of various parts of the brain. Some researchers argue that hypoxia results in hippocampal damage, thus contributing to vulnerability for schizophrenia. Low birth weight, a neonatal complication, is another potential early factor contributing to schizophrenia. There is evidence that low birth weight is related to increased ventricular size, which is a common characteristic of schizophrenia patients.

The findings on prenatal complications support the notion that fetal brain development may be disrupted in individuals who later manifest schizophrenia. A central question raised by these findings concerns the nature of the etiologic role of OCs. Some hypothesize that OCs produce the neural predisposition to schizophrenia, whereas others posit that OCs exacerbate or interact with an existing genetic predisposition.

Findings from prospective, high-risk research projects lend support to the hypothesis that OCs interact with genetic vulnerabilities in the etiology of schizophrenia. High-risk studies involve the repeated assessment of children of schizophrenia patients, based on the expectation that a larger percentage of these children will eventually develop the illness than individuals in the general population. The high-risk method offers some advantages when compared with retrospective studies of the precursors of schizophrenia. One advantage is that it allows for the direct assessment of subjects in the premorbid period, as well as the selection and study of variables that are thought to have prognostic relevance. Furthermore, because a significant portion of the data collection takes place during the premorbid period, this reduces confounds that often occur in the study of diagnosed patients (e.g., medication and institutionalization).

Studies using the high-risk method have shown an interactive effect of genetic risk and exposure to OCs in predicting adult psychiatric outcome. In other words, the correlation between OCs and adult psychiatric symptoms was greater for offspring of schizophrenia parents than for children of healthy parents. The same pattern was apparent for the relation between OCs and adult brain morphology, suggesting that pre- and perinatal factors contribute to brain abnormalities.

As noted earlier, prenatal exposure to maternal viral infection has also been linked with schizophrenia. Specifically, the rate of schizophrenia is increased for cohorts who were in the second trimester during flu epidemics. Another source of evidence for the viral hypothesis is the finding that the births of schizophrenia patients do not seem to be randomly distributed throughout the course of the year. Instead, the births of schizophrenia patients occur more frequently in winter months.

Some researchers have suggested that postnatal viral infection may also be relevant to schizophrenia, and that the illness may be caused by a long-acting virus. This hypothesis claims that “slow viruses,” which are active over a long period of time, interact with a genetic predisposition to produce schizophrenia. Various findings are cited in support of this hypothesis. Some researchers have identified a viral infection in fatal catatonia, a disorder characterized by schizophrenia-like symptoms, suggesting that a similar viral infection may be found for schizophrenia. Other researchers have found signs of viral activity in the cerebrospinal fluid of patients with schizophrenia.

The diathesis-stress model has dominated theories about the etiology of schizophrenia for several decades. This model assumes that certain individuals inherit or acquire a vulnerability to schizophrenia (the diathesis), and that the behavioral expression of this vulnerability is determined or triggered by environmental stressors. Although “stress” was originally conceptualized as psychosocial in origin, contemporary versions of this model broaden the definition of stress to include prenatal and postnatal insults to the central nervous system. Thus the diathesis, combined with exposure to environmental stressors, can produce schizophrenia.

Exposure to stress within the context of the family has been the focus of researchers in the field. Families in which there is a schizophrenia patient show more conflict and abnormalities in communication than do other families. However, it has also been shown that there is greater conflict and more abnormalities of communication in families in which any member has a severe debilitating illness. Thus, family communication styles are unlikely to play a unique causal role in schizophrenia.

There is good evidence, however, that exposure to high levels of criticism from family members can increase the likelihood of relapse in schizophrenia patients. The number of critical comments, expressions of hostility, and emotional overinvolvement comprise a construct referred to as expressed emotion (EE). Recovering schizophrenia patients in families high in EE are much more likely to have a relapse compared with patients in families low in EE. There is also evidence from studies of the adopted offspring of schizophrenia patients suggesting that familial stress can hasten the onset of symptoms.

Before 1900, knowledge of the nature and causes of mental disorders was limited. Individuals with psychiatric symptoms, particularly psychotic symptoms, were typically viewed by others with disdain or amusement. However, social trends and advances in medical knowledge converged to produce greater sympathy for those with mental illness. This led, especially during the early part of the century, to the construction of public and private hospitals devoted to the care of the mentally ill.

Today, most schizophrenia patients experience at least one period of inpatient treatment. This is typically precipitated by the first psychotic episode. During this initial hospitalization, an extensive assessment is usually conducted to determine the most appropriate diagnosis. Treatment is then initiated to reduce symptoms and stabilize patients so that they can return to the community as soon as possible.

In the past, periods of hospitalization were longer in duration than they are today. This is due, in part, to the availability today of better medical treatments. Another factor that has contributed to shorter hospital stays is the deinstitutionalization movement. Initially spurred by concerns that too many of the mentally ill were becoming “institutionalized” and were losing their ability to function in the community, financial support for state psychiatric hospitals was gradually cut. But community support services and transitional living arrangements were not readily available to many patients. As a result, former psychiatric inpatients now constitute a substantial proportion of the homeless found in U.S. cities.

Introduced in the 1950s, antipsychotic medication has since become the most effective and widely used treatment for schizophrenia. Research indicated that the “typical” antipsychotics, such as haloperidol, decreased the symptoms of schizophrenia, especially positive symptoms, and reduced the risk of relapse. However, they were not as effective in reducing the negative symptoms. Furthermore, some patients showed no response to antipsychotic drugs.

Chlorpromazine (Thorazine) was among the first antipsychotic commonly used to treat schizophrenia. Since the 1950s, many other antipsychotic drugs have been introduced. Like chlorpromazine, these drugs reduce hallucinations, delusions, and thought disorder, and engender more calm, manageable, and socially appropriate behavior. As mentioned, all currently used antipsychotic drugs block dopamine neurotransmission. Thus it has been assumed that their efficacy is due to their capacity to reduce the overactivation of dopamine pathways in the brain.

Unfortunately, the benefits of standard or typical antipsychotic drugs are often mitigated by side effects. Minor side effects include sensitivity to light, dryness of mouth, and drowsiness. The more severe effects are psychomotor dysfunction, skin discoloration, visual impairment, and tardive dyskinesia (an involuntary movement disorder that can appear after prolonged use of antipsychotics). It is especially unfortunate that tardive dyskinesia is sometimes irreversible when patients are withdrawn from neuroleptics. Many of these physical signs are known to be caused by chronic blockade of dopamine pathways. Although additional medications can counter some of the negative effects of the typical antipsychotics, schizophrenia patients often resist taking them because of an aversion to the side effects.

Within the past decade, some new, “atypical” antipsychotic drugs have been introduced. It was hoped that these drugs would be effective in treating patients who had not responded to standard antipsychotics. Also, researchers hoped to identify medications that had fewer side effects. One example is Clozapine, released in 1990, which seems to reduce negative symptoms more effectively than typical antipsychotic drugs. Clozapine not only offers hope for patients who are nonresponsive to other medications, but it also has fewer side effects than typical antipsychotics. However, clozapine can produce one rare, but potentially fatal, side effect, agranulocytosis, a blood disorder. Consequently, patients who are on this medication must be monitored on a regular basis. It is fortunate that several other new antipsychotic medications have recently become available, and some of these appear to have no serious side effects.

It appears that it is important to begin pharmacological treatment of schizophrenia as soon as possible after the symptoms are recognized. The longer patients go without treatment of illness episodes, the worse the long-term prognosis. Medication also has the benefit of lowering the rate of mortality, particularly suicide, among schizophrenia patients. Patients who are treated with antipsychotic medication generally require maintenance of the medication to obtain continued relief from symptoms. Medication withdrawal often results in relapse. At the same time, the associated long- and short-term side effects of antipsychotics, especially the typical antipsychotics, are of continuing concern to patients, their families, and physicians. It is possible that future research on the neural mechanisms involved in schizophrenia will lead to the development of novel treatments that eliminate the need for maintenance medication.

Many schizophrenia patients also suffer from depression and, as noted, are at elevated risk for suicide. The reason or reasons for the high rate of co-occurance of depression with schizophrenia is not known. Given the debilitating and potentially chronic nature of schizophrenia, however, it is likely that some patients experience depressive symptoms in response to their condition. For others, depressive symptoms may be medication side effects or a manifestation of a biologically based vulnerability to depression.

Clinicians have used various forms of psychological therapy in an effort to treat schizophrenia patients. Early attempts to provide therapy for schizophrenia patients relied on insight-oriented or psychodynamic techniques. The chief goal was to foster introspection and self-understanding in patients. Research findings provided no support for the efficacy of these therapies in the treatment of schizophrenia.

It has been shown, however, that supportive therapy can be a useful adjunct to medication in the treatment of patients. Similarly, psychoeducational approaches that emphasize providing information about symptom management have proven effective in reducing relapse. Among the most beneficial forms of psychological treatment is behavioral therapy. Some psychiatric hospitals have established programs in which patients earn credits or “tokens” for appropriate behavior and then redeem these items for privileges or tangible rewards. These programs can increase punctuality, hygiene, and other socially acceptable behaviors in patients.

In recent years, family therapy has become a standard component of the treatment of schizophrenia. These family therapy sessions are psychoeducational in nature and are intended to provide the family with support, information about schizophrenia, and constructive guidance in dealing with the illness in a family member. In this way, family members become a part of the treatment process and learn new ways to help their loved one cope with schizophrenia.

Another critical component of effective treatment is the provision of rehabilitative services. These services take the form of structured residential settings, independent life-skills training, and vocational programs. Such programs often play a major role in helping patients recover from their illness.

It is now firmly established that schizophrenia is caused by an abnormality of brain function that in most cases has its origin in early brain insults, inherited vulnerabilities, or both. But the identification of the causal agents and the specific neural substrates responsible for schizophrenia must await the findings of future research. There is reason to be optimistic about future research progress. New technologies are available for examining brain structure and function. In addition, dramatic advances in neuroscience have expanded our understanding of the brain and the impact of brain abnormalities on behavior. We are likely to witness great strides in our understanding of the causes of all mental illnesses within the coming decades.

It is hoped that advances will also be made in the treatment of schizophrenia. New drugs are being developed at a rapid pace, and more effective medications are likely to result. At the same time, advocacy efforts on the part of patients and their families have resulted in improvements in services. But a further expansion of services is greatly needed to provide patients with the structured living situations and work environments they need to make the transition into independent community living.

Bibliography:

Breier, A. (Ed.). (1996). The new pharmacotherapy of schizophrenia. Washington DC: American Psychiatric Press.
Keefe, R. S., & Harvey, P. (1994). Understanding schizophrenia: A guide to the new research on causes and treatment. New York: Free Press.
Miller, G. A. (Ed.). (1995). The behavioral high-risk paradigm in psychopathology. New York: Springer.
Shriqui, C. L., & Nasrallah, H. A. (Eds.). (1995). Contemporary issues in the treatment of schizophrenia. Washington DC: American Psychiatric Press.
Torrey, E. F. (1994). Schizophrenia and manic-depressive disorder: The biological roots of mental illness as revealed by the landmark study of identical twins. New York: Basic Books.
Walker, E. F. (1991). Schizophrenia: A life-course developmental perspective. New York: Academic Press.

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Schizophrenia

What is schizophrenia.

Schizophrenia is a serious mental illness that affects how a person thinks, feels, and behaves. People with schizophrenia may seem like they have lost touch with reality, which can be distressing for them and for their family and friends. The symptoms of schizophrenia can make it difficult to participate in usual, everyday activities, but effective treatments are available. Many people who receive treatment can engage in school or work, achieve independence, and enjoy personal relationships.

What are the signs and symptoms of schizophrenia?

It’s important to recognize the symptoms of schizophrenia and seek help as early as possible. People with schizophrenia are usually diagnosed between the ages of 16 and 30, after the first episode of psychosis . Starting treatment as soon as possible following the first episode of psychosis is an important step toward recovery. However, research shows that gradual changes in thinking, mood, and social functioning often appear before the first episode of psychosis. Schizophrenia is rare in younger children.

Schizophrenia symptoms can differ from person to person, but they generally fall into three main categories: psychotic, negative, and cognitive.

Psychotic symptoms include changes in the way a person thinks, acts, and experiences the world. A person experiencing psychotic symptoms often has disrupted thoughts and perceptions, and they may have difficulty recognizing what is real and what is not. Psychotic symptoms include:

Hallucinations : When a person sees, hears, smells, tastes, or feels things that are not actually there. Hearing voices is common for people with schizophrenia. People who hear voices may hear them for a long time before family or friends notice a problem.
Delusions : When a person has strong beliefs that are not true and may seem irrational to others. For example, individuals experiencing delusions may believe that people on the radio and television are sending special messages that require a certain response, or they may believe that they are in danger or that others are trying to hurt them.
Thought disorder : When a person has ways of thinking that are unusual or illogical. People with thought disorder may have trouble organizing their thoughts and speech. Sometimes a person will stop talking in the middle of a thought, jump from topic to topic, or make up words that have no meaning.

Negative symptoms include loss of motivation, loss of interest or enjoyment in daily activities, withdrawal from social life, difficulty showing emotions, and difficulty functioning normally.

Negative symptoms include:

Having trouble planning and sticking with activities, such as grocery shopping
Having trouble anticipating and being motivated by pleasure in everyday life
Talking in a dull voice and showing limited facial expression
Avoiding social interaction or interacting in socially awkward ways
Having very low energy and spending a lot of time in passive activities. In extreme cases, a person might stop moving or talking for a while, which is a rare condition called catatonia .

These symptoms are sometimes mistaken for symptoms of depression or other mental illnesses.

Cognitive symptoms include problems in attention, concentration, and memory. These symptoms can make it hard to follow a conversation, learn new things, or remember appointments. A person’s level of cognitive functioning is one of the best predictors of their day-to-day functioning. Health care providers evaluate cognitive functioning using specific tests.

Cognitive symptoms include:

Having trouble processing information to make decisions
Having trouble using information immediately after learning it
Having trouble focusing or paying attention

The Centers for Disease Control and Prevention (CDC) has recognized that having certain mental disorders, including depression and schizophrenia, can make people more likely to get severely ill from COVID-19. Learn more about getting help and finding a health care provider .

Risk of violence

Most people with schizophrenia are not violent. Overall, people with schizophrenia are more likely than those without the illness to be harmed by others. For people with schizophrenia, the risk of self-harm and of violence to others is greatest when the illness is untreated or co-occurs with alcohol or substance misuse. It is important to help people who are showing symptoms to get treatment as quickly as possible.

Schizophrenia vs. dissociative identity disorder

Although some of the signs may seem similar on the surface, schizophrenia is not dissociative identity disorder (which used to be called multiple personality disorder or split personality). People with dissociative identity disorder have two or more distinct identities with distinct behaviors and memories.

What are the risk factors for schizophrenia?

Several factors may contribute to a person’s risk of developing schizophrenia.

Genetics: Schizophrenia sometimes runs in families. However, just because one family member has schizophrenia, it does not mean that other members of the family also will have it. Studies suggest that many different genes may increase a person’s chances of developing schizophrenia , but that no single gene causes the disorder by itself.

Environment: Research suggests that a combination of genetic factors and aspects of a person’s environment and life experiences may play a role in the development of schizophrenia. These environmental factors that may include living in poverty, stressful or dangerous surroundings, and exposure to viruses or nutritional problems before birth.

Brain structure and function: Research shows that people with schizophrenia may be more likely to have differences in the size of certain brain areas and in connections between brain areas. Some of these brain differences may develop before birth. Researchers are working to better understand how brain structure and function may relate to schizophrenia.

How is schizophrenia treated?

Current treatments for schizophrenia focus on helping people manage their symptoms, improve day-to-day functioning, and achieve personal life goals, such as completing education, pursuing a career, and having fulfilling relationships.

Antipsychotic medications

Antipsychotic medications can help make psychotic symptoms less intense and less frequent. These medications are usually taken every day in a pill or liquid forms. Some antipsychotic medications are given as injections once or twice a month.

If a person’s symptoms do not improve with usual antipsychotic medications, they may be prescribed clozapine. People who take clozapine must have regular blood tests to check for a potentially dangerous side effect that occurs in 1-2% of patients.

People respond to antipsychotic medications in different ways. It is important to report any side effects to a health care provider. Many people taking antipsychotic medications experience side effects such as weight gain, dry mouth, restlessness, and drowsiness when they start taking these medications. Some of these side effects may go away over time, while others may last.

Shared decision making between health care providers and patients is the recommended strategy for determining the best type of medication or medication combination and the right dose. To find the latest information about antipsychotic medications, talk to a health care provider and visit the U.S. Food and Drug Administration (FDA) website .

Psychosocial treatments

Psychosocial treatments help people find solutions to everyday challenges and manage symptoms while attending school, working, and forming relationships. These treatments are often used together with antipsychotic medication. People who participate in regular psychosocial treatment are less likely to have symptoms reoccur or to be hospitalized.

Examples of this kind of treatment include types of psychotherapy such as cognitive behavioral therapy, behavioral skills training, supported employment, and cognitive remediation interventions.

Education and support

Educational programs can help family and friends learn about symptoms of schizophrenia, treatment options, and strategies for helping loved ones with the illness. These programs can help friends and family manage their distress, boost their own coping skills, and strengthen their ability to provide support. The National Alliance on Mental Illness website has more information about support groups and education .

Coordinated specialty care

Coordinated specialty care (CSC) programs are recovery-focused programs for people with first episode psychosis, an early stage of schizophrenia. Health care providers and specialists work together as a team to provide CSC, which includes psychotherapy, medication, case management, employment and education support, and family education and support. The treatment team works collaboratively with the individual to make treatment decisions, involving family members as much as possible.

Compared with typical care, CSC is more effective at reducing symptoms, improving quality of life, and increasing involvement in work or school.

Assertive community treatment

Assertive community treatment (ACT) is designed especially for people with schizophrenia who are likely to experience multiple hospitalizations or homelessness. ACT is usually delivered by a team of health care providers who work together to provide care to patients in the community.

Treatment for drug and alcohol misuse

People with schizophrenia may also have problems with drugs and alcohol. A treatment program that includes treatment for both schizophrenia and substance use is important for recovery because substance use can interfere with treatment for schizophrenia.

How can I find help for schizophrenia?

If you have concerns about your mental health, talk to a primary care provider. They can refer you to a qualified mental health professional, such as a psychologist, psychiatrist, or clinical social worker, who can help you figure out the next steps. Find tips for talking with a health care provider about your mental health.

You can learn more about getting help on the NIMH website. You can also learn about finding support and locating mental health services in your area on the Substance Abuse and Mental Health Services Administration (SAMHSA) website.

It can be difficult to know how to help someone who is experiencing psychosis.

Here are some things you can do:

Help them get treatment and encourage them to stay in treatment.
Remember that their beliefs or hallucinations seem very real to them.
Be respectful, supportive, and kind without tolerating dangerous or inappropriate behavior.
Look for support groups and family education programs, such as those offered by the National Alliance on Mental Illness .

If you or someone you know is struggling or having thoughts of suicide, call or text the 988 Suicide & Crisis Lifeline at 988 or chat at 988lifeline.org . In life-threatening situations, call 911 .

How can I find a clinical trial for schizophrenia?

Clinical trials are research studies that look at new ways to prevent, detect, or treat diseases and conditions. The goal of clinical trials is to determine if a new test or treatment works and is safe. Although individuals may benefit from being part of a clinical trial, participants should be aware that the primary purpose of a clinical trial is to gain new scientific knowledge so that others may be better helped in the future.

Researchers at NIMH and around the country conduct many studies with patients and healthy volunteers. We have new and better treatment options today because of what clinical trials uncovered years ago. Talk to your health care provider about clinical trials, their benefits and risks, and whether one is right for you.

To learn more or find a study, visit:

NIMH’s Clinical Trials webpage : Information about participating in clinical trials
Clinicaltrials.gov: Current Studies on Schizophrenia : List of clinical trials funded by the National Institutes of Health (NIH) being conducted across the country
Join a Study: Schizophrenia : List of studies being conducted on the NIH Campus in Bethesda, MD

Where can I learn more about schizophrenia?

Free brochures and shareable resources.

Schizophrenia : This brochure on schizophrenia offers basic information on signs and symptoms, treatment, and finding help. Also available en español .
Understanding Psychosis : This fact sheet presents information on psychosis, including causes, signs and symptoms, treatment, and resources for help. Also available en español .
Digital Shareables on Schizophrenia : These digital resources, including graphics and messages, can be used to spread the word about schizophrenia and help promote schizophrenia awareness and education in your community.

Research and statistics

Accelerating Medicines Partnership® Program - Schizophrenia (AMP® SCZ) : This AMP public-private collaborative effort aims to promote the development of effective, targeted treatments for those at risk of developing schizophrenia. More information about the program is also available on the AMP SCZ website .
Early Psychosis Intervention Network (EPINET) : This broad research initiative aims to develop models for the effective delivery of coordinated specialty care services for early psychosis.
Journal Articles: This webpage provides information on references and abstracts from MEDLINE/PubMed (National Library of Medicine).
Psychotic Disorders Research Program : This program supports research into the origins, onset, course, and outcome of schizophrenia spectrum disorders and other psychotic illnesses.
Risk and Early Onset of Psychosis Spectrum Disorders Program : This program supports research on childhood and adolescent psychosis and thought disorders.
Recovery After an Initial Schizophrenia Episode (RAISE) : The NIMH RAISE research initiative included two studies examining different aspects of coordinated specialty care treatments for people who were experiencing early psychosis.
Statistics: Schizophrenia : This webpage provides the statistics currently available on the prevalence and treatment of schizophrenia among people in the United States.
NIMH Experts Discuss Schizophrenia : Learn the signs and symptoms, risk factors, treatments of schizophrenia, and the latest NIMH-supported research in this area.

Last Reviewed: April 2024

Unless otherwise specified, the information on our website and in our publications is in the public domain and may be reused or copied without permission. However, you may not reuse or copy images. Please cite the National Institute of Mental Health as the source. Read our copyright policy to learn more about our guidelines for reusing NIMH content.

Broadband Internet Access, Economic Growth, and Wellbeing

Between 2000 and 2008, access to high-speed, broadband internet grew significantly in the United States, but there is debate on whether access to high-speed internet improves or harms wellbeing. We find that a ten percent increase in the proportion of county residents with access to broadband internet leads to a 1.01 percent reduction in the number of suicides in a county, as well as improvements in self-reported mental and physical health. We further find that this reduction in suicide deaths is likely due to economic improvements in counties that have access to broadband internet. Counties with increased access to broadband internet see reductions in poverty rate and unemployment rate. In addition, zip codes that gain access to broadband internet see increases in the numbers of employees and establishments. In addition, heterogeneity analysis indicates that the positive effects are concentrated in the working age population, those between 25 and 64 years old. This pattern is precisely what is predicted by the literature linking economic conditions to suicide risk.

We are grateful to participants at the Association of Public Policy and Management and the Washington Area Labor Symposium conferences for their helpful comments. Any errors or conclusions are our own. The views expressed herein are those of the authors and do not necessarily reflect the views of the National Bureau of Economic Research.

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Brendan Kelly is professor of Psychiatry, holds advanced degrees in history, psychiatry and law. This interdisciplinary perspective is evident in his extensive publications on the history of psychiatry and mental illnesses in Ireland. As a public intellectual, he has addressed topics such as the impact of Covid-19 on mental health, schizophrenia, and Ireland’s history of institutional confinement, particularly the history of Grangegorman Asylum.

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Current Concepts and Treatments of Schizophrenia

Piotr stępnicki.

1 Department of Synthesis and Chemical Technology of Pharmaceutical Substances, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodzki St., PL-20093 Lublin, Poland; [email protected] (P.S.); [email protected] (M.K.)

Magda Kondej

Agnieszka a. kaczor.

2 School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627, FI-70211 Kuopio, Finland

Schizophrenia is a debilitating mental illness which involves three groups of symptoms, i.e., positive, negative and cognitive, and has major public health implications. According to various sources, it affects up to 1% of the population. The pathomechanism of schizophrenia is not fully understood and current antipsychotics are characterized by severe limitations. Firstly, these treatments are efficient for about half of patients only. Secondly, they ameliorate mainly positive symptoms (e.g., hallucinations and thought disorders which are the core of the disease) but negative (e.g., flat affect and social withdrawal) and cognitive (e.g., learning and attention disorders) symptoms remain untreated. Thirdly, they involve severe neurological and metabolic side effects and may lead to sexual dysfunction or agranulocytosis (clozapine). It is generally agreed that the interactions of antipsychotics with various neurotransmitter receptors are responsible for their effects to treat schizophrenia symptoms. In particular, several G protein-coupled receptors (GPCRs), mainly dopamine, serotonin and adrenaline receptors, are traditional molecular targets for antipsychotics. Comprehensive research on GPCRs resulted in the exploration of novel important signaling mechanisms of GPCRs which are crucial for drug discovery: intentionally non-selective multi-target compounds, allosteric modulators, functionally selective compounds and receptor oligomerization. In this review, we cover current hypotheses of schizophrenia, involving different neurotransmitter systems, discuss available treatments and present novel concepts in schizophrenia and its treatment, involving mainly novel mechanisms of GPCRs signaling.

1. Introduction

Schizophrenia is an important health issue, affecting almost 1% of the population, frequently with significant social and economic implications, as patients often suffer from unemployment and are homeless. Moreover, antipsychotics prescribed to treat schizophrenia are used in bipolar affective disorder, which has a prevalence of 2.3% in the population. Consequently, about 16.5 million patients in the EU need antipsychotics on a daily basis. This generates a significant healthcare costs, as central nervous system (CNS) disorders are among the most costly medical conditions (EUR 386 billion annually in the EU) [ 1 ]. Current treatments of schizophrenia have significant limitations. Firstly, they are efficient for only about half of patients enabling them independent life [ 2 ]. Secondly, they ameliorate mainly positive symptoms (e.g., hallucinations and thought disorders which are the core of the disease) but negative (e.g., flat affect and social withdrawal) and cognitive (e.g., learning and attention disorders) symptoms remain untreated [ 3 ]. Thirdly, they involve severe neurological and metabolic side effects and may lead to sexual dysfunction or agranulocytosis (clozapine) [ 4 ]. The reason for only partial effectiveness of current antipsychotics is the pathomechanism of schizophrenia which is not adequately understood due to its complexity and involvement of many molecular targets.

The current understanding of schizophrenia is constituted by the dopaminergic hypothesis which denotes alterations of dopamine neurotransmission in the mesolimbic system responsible for positive symptoms and mesocortical pathway, causing negative symptoms, complemented by the glutamatergic hypothesis which considers changes in prefrontal neuronal connectivity involving glutamatergic neurotransmission at NMDA receptor [ 5 ]. In particular, increased presynaptic dopamine synthesis is relevant for the pathogenesis of schizophrenia [ 6 ]. The methods of treatment of schizophrenia are classified as the first (mainly dopamine D 2 receptor antagonists), second (multi-target antagonists with greater antagonism at serotonin 5-HT 2A receptor than at dopamine D 2 receptor) and third generation antipsychotics represented, e.g., by aripiprazole, brexpiprazole and cariprazine. Aripiprazole is a partial dopamine D 2 receptor agonist in G α pathway but it can display agonist, partial agonist or antagonist activity at dopamine D 2 receptor upon different signaling readouts [ 7 ]. In particular it is an antagonist or a partial agonist for β-arrestin-2 signaling pathway [ 7 ].

As G protein-coupled receptors (GPCRs) are classical and well-validated targets for antipsychotics, the elaboration of concepts on the nature of GPCR signaling opens novel and unexplored possibilities for more effective and safer antipsychotics. GPCR functioning is conceptualized by the ternary complex model which involves activation of the receptor by an agonist and transmission of the signal to G protein. However, it was reported that many GPCR ligand display high degree of promiscuity which was considered a drawback in GPCR-oriented drug discovery [ 8 ]. In many complex diseases including schizophrenia, the single target drugs turned out a failure, whereas multi-target drugs are much more efficient [ 9 ]. Clozapine has a low nanomolar affinity to several aminergic GPCRs which reflexes the complex pathomechanism of the disease.

Another important breakthrough in the field was discovery that a specific receptor can couple to a few G proteins and can signal independently on G proteins by occurring in an ensemble of conformations which trigger interaction with biased ligands to downstream effectors. This phenomenon is termed the functional selectivity [ 10 , 11 ] and may lead to safer drugs thanks to selective modulation of one pathway over another one. In the field of dopamine D 2 ligands as antipsychotics, it was found that many clinically useful drugs are antagonists of β-arrestin recruitment [ 12 ]. Contrarily, it was also reported that dopamine D 2 receptor ligands which are antagonists of Gα i/o pathway and agonists of β-arrestin pathway may display beneficial antipsychotic properties with diminished extrapyramidal unwanted effects in animal models [ 7 ].

Allosteric modulation of GPCRs has lately been a hot topic in GPCR-oriented drug discovery [ 13 , 14 ] as allosteric mode of action brings important advantages over orthosteric drugs: better receptor or even pathway selectivity and fewer side effects and ceiling effect reducing the risk of overdosage [ 15 ]. This approach has not yet been exploited for antipsychotics, however a positive allosteric modulator (PAM) of dopamine D 2 receptor, a peptidomimetic PAOPA, was proven efficient in attenuating symptoms of schizophrenia in animal models [ 16 ]. Few small molecule negative allosteric modulators (NAMs) of dopamine D 2 receptor are known (SB269,652 [ 17 ]; homocysteine and analogs [ 18 ]) and their usefulness in schizophrenia needs to be further evaluated.

Finally, targeting heterodimers of dopamine D 2 receptor which are distinct pharmacological entities, in particular adenosine A 2A –D 2 and serotonin 5HT 2A –D 2 heterodimers with bivalent ligands, dimer-specific monovalent ligands, compounds causing ligand-induced dimerization and peptides, peptidomimetics or small molecules disrupting dimer interface may lead to better pharmaceutics with higher selectivity and tissue specificity [ 19 , 20 ]. Among compounds targeting these dimers only bivalent ligands (not drug-like due to high molecular weight) are relatively easy to design. Compounds from other groups are not known either for D 2 dimers (dimer-specific monovalent ligands and ligands inducing dimerization) or in the whole GPCR family (small molecules disrupting dimer interface). It was only reported that peptides, corresponding to the dopamine D 2 receptor transmembrane regions TMVI and TMVII, effectively dissociated the dimer [ 21 ].

In this review, we cover current hypotheses of schizophrenia, involving different neurotransmitter systems, discuss available treatments and present novel concepts in schizophrenia and its treatment, involving mainly novel mechanisms of GPCRs signaling.

2. Schizophrenia as a Complex Disease

2.1. dopaminergic hypothesis.

The dopaminergic hypothesis of schizophrenia is the fundament of the investigation and treatment of schizophrenia [ 22 ]. The first version of this hypothesis stressed the role of the excess of dopamine but it was developed into an idea linking prefrontal hypodopaminergia and striatal hyperdopaminergia and then to the current aberrant salience hypothesis [ 22 ].

The dopaminergic hypothesis of schizophrenia was proposed for the first time in the 1960s when chlorpromazine was introduced as the first antipsychotic and proved to treat positive symptoms of the disease [ 23 ]. Subsequently, the discovery that amphetamine produces psychosis was another proof for a role of excessive dopamine in schizophrenia. It was thus proposed that the increased dopamine neurotransmission might be a reason of this disease. The advancement of novel antipsychotics was in accordance with the dopaminergic hypothesis of schizophrenia as it was observed that positive symptoms of the disease can be attenuated with dopamine receptor antagonists. However, some findings contradicted this hypothesis, e.g., clozapine, which is a very effective antipsychotic in patients with resistant schizophrenia, has rather low affinity to dopamine D 2 receptors. Moreover, some patients with schizophrenia also have normal level of dopamine metabolites in cerebrospinal fluid or serum. These contradictions and novel findings from PET studies led Davis et al. [ 24 ] to propose that schizophrenia involves diminished frontal and increased striatal dopaminergic neurotransmission. Moreover, they linked the positive symptoms of the disease with the striatal dopamine D 2 receptor overactivation resulting from hyperactive mesolimbic dopamine projections while negative and cognitive symptoms result from the prefrontal cortex dopamine D 1 receptor hypostimulation due to diminished mesocortical dopamine projections [ 22 , 24 ]. Further reformulation of this hypothesis has been reported [ 25 ].

Nowadays, aberrant salience hypothesis of psychosis most commonly links the dopaminergic system with the symptoms of schizophrenia. It is based on the incentive salience hypothesis [ 26 ] which suggests that the mesolimbic dopaminergic neurotransmission is crucial in the attribution of salience which governs attention and affects decision making and functioning [ 22 ]. The aberrant salience hypothesis assumes that the attribution of salience is disturbed by excessive dopamine firing in psychotic episode, while, in healthy individuals, dopamine is responsible for mediating contextually appropriate saliences [ 27 ]. This revised version of dopaminergic hypothesis of schizophrenia may explain some clinical and pharmacological features of the disease, i.e., why the schizophrenia patients do not develop all symptoms of psychosis at once or why antipsychotics exert their therapeutic effects after weeks [ 22 ]. Moreover, it can also shed new light on the side effect of diminished motivation in patients with antipsychotics medication and on the recurrence of psychosis after drug withdrawal.

As mentioned above, the dopamine D 2 receptor is a drug target for all drugs against schizophrenia currently present on the market. First- and second-generation antipsychotics are dopamine D 2 receptor antagonists while third-generation drugs are partial agonists or biased ligands of this receptor. Many drugs applied to treat schizophrenia are antagonists of D 2 -like (D 2 , D 3 and D 4 ) dopamine receptor subtypes [ 28 ]. As dopamine receptor play a key role in coordination of movement, memory and cognition, emotion and affect, and the regulation of prolactin secretion, blockade D 2 -like receptors may result in side effects linked with the long-lasting antipsychotics medication. This involves parkinsonian-like extrapyramidal symptoms typically resulting from the application of the first-generation antipsychotics and metabolic side effects (weight gain, hyperglycemia, increased risk of diabetes mellitus, dyslipidemia and gynecomastia) linked with the second-generation antipsychotics [ 28 ]. In this regard, there are some reports which indicate that D 3 versus D 2 dopamine receptor selective ligands may be an interesting alternative to treat schizophrenia [ 28 ]. It has also been found that the antagonism of dopamine D 3 receptor may be partially responsible for blonanserin-caused cortical dopamine and acetylcholine efflux and cognitive improvement [ 29 ]. Importantly, selective dopamine D 3 receptor antagonists are not efficient in antipsychotic animal models based on D 2 receptor antagonism [ 30 ]. On the other hand, selective D 3 receptor antagonists influence dopaminergic neurons electrical activity in the ventral tegmental area in the way characteristic for the second-generation antipsychotics, neutralize NMDA glutamate receptor blockade effects, and increase cortical dopamine and acetylcholine in microdialysis [ 30 ]. Contrary to dopamine D 2 receptor antagonists, D 3 antagonists beneficially affect several cognitive and social features in animal models, e.g., cognitive flexibility and executive function, that are deteriorated in patients with schizophrenia [ 30 ].

It was also demonstrated that prolonged dopamine D 2 receptor blockade leads to downregulation of D 1 receptors in the prefrontal cortex and, consequently, results in significant deterioration of working memory [ 31 ]. Thus, agonism at D 1 receptors in the prefrontal cortex can have a key role in working memory and thus D 1 receptor might be a target of choice for treating cognitive deficits in schizophrenia [ 32 ].

It should be stressed that, despite a key role of dopamine in the pathomechanism and clinical practice of schizophrenia, dopamine allows understanding the pathophysiology of the disease but not the reason per se [ 22 ]. In this context, dopamine functions as the common final pathway for a number of contributing environmental and/or genetic factors [ 22 ]. Thus, other neurotransmitters, in particular glutamate, are important for the pathomechanism of schizophrenia.

2.2. Glutamatergic Hypothesis

Glutamate belongs to the main excitatory neurotransmitters and is the most common neurotransmitter in the mammalian brain [ 33 ]. Glutamatergic pathways linking to the cortex, the limbic system, and the thalamus regions are important in schizophrenia [ 34 , 35 ]. Disturbances in the glutamatergic neurotransmission may influence synaptic plasticity and cortical microcircuitry, especially NMDA receptor functioning [ 36 ]. NMDA receptors belong to ligand-gated ion channels, and are important for excitatory neurotransmission, excitotoxicity and plasticity [ 37 , 38 ]. NMDA-receptor antagonists, e.g., phencyclidine and ketamine, can mimic psychosis with similar symptoms as in schizophrenia [ 39 ]. Moreover, in therapeutic trials substances which increase NMDA receptor signaling were reported to attenuate some symptoms in patients with schizophrenia [ 40 ]. Next, in postmortem studies, some disturbances in glutamatergic receptor density and subunit composition in the prefrontal cortex, thalamus, and temporal lobe were found [ 38 , 39 , 40 ] and these are brain regions with distorted stimulation while cognitive actions are performed by schizophrenia patients [ 41 , 42 , 43 , 44 ]. NMDA-receptor hypofunction state can lead to morphological and structural brain changes which can result in the development of psychosis [ 45 , 46 ]. It was hypothesized that levels of glutamate lower with age in healthy people, but it was not determined how they are affected by the chronic illness [ 47 ].

Antipsychotics may influence glutamate transmission by affecting the release of glutamate, by interaction with glutamatergic receptors, or by changing the density or subunit composition of glutamatergic receptors [ 35 ]. It was demonstrated that antipsychotics interacting with dopamine D 2 receptor enhance the phosphorylation of the NR1 subunit of the NMDA receptor, thus reinforce its activation and consequent gene expression [ 48 ]. In this context, dopamine–glutamate interactions occur intraneuronally and intrasynaptically. There are also reports that action of some second-generation antipsychotics on NMDA receptors might be different from the effect of the first generation antipsychotics on this receptor [ 49 ]. Antipsychotics also influence glutamate transmission by acting on serotonin receptors [ 50 ].

Disturbances in glutamate signaling may be an attractive drug target for schizophrenia due to its key role in the pathomechanism of this disease in terms of cognitive impairment and negative symptoms [ 34 , 35 ]. Findings for hypoactivity of NMDA receptors in schizophrenia stimulated the clinical trials with substances activating this receptor [ 35 ]. Classical agonists at the NMDA are not useful here as excessive stimulation of NMDA receptors results in excitotoxicity and neuron damage. The glycine modulatory binding pocket on the NMDA receptor can be considered a more promising target. Similarly, positive allosteric modulators of another family of ionotropic glutamatergic receptors, i.e., α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors [ 51 , 52 ] as well as positive allosteric modulators of metabotropic glutamatergic receptors [ 53 ], might be considered promising new treatments of schizophrenia in accordance with the glutamatergic hypothesis of this disease.

2.3. Serotoninergic Hypothesis of Schizophrenia

The serotonin hypothesis of schizophrenia is derived from the reports about the mechanism of action of the hallucinogenic drug lysergic acid diethylamide (LSD) and its linkage to serotonin [ 54 ]. Consideration of the psychotic effects of LSD and the antipsychotic effects of, e.g., risperidone and clozapine, which are dopamine-serotonin receptor ligands, stimulated the research on connections between these neurotransmitters as a drug target in schizophrenia [ 55 ].

It was suggested that the overload of serotonin from the dorsal raphe nucleus (DRN) resulting from stress can disturb the activity of cortical neurons in schizophrenia [ 56 ]. Moreover, long-lasting extensive stress-derived serotonergic overload in the cerebral cortex in schizophrenia, in particular in the anterior cingulate cortex (ACC) and dorsolateral frontal lobe (DLFL), may be a key reason of this disorder [ 57 ].

Serotonin antagonists improve the extrapyramidal side effects of antipsychotics. Despite the lack of absolute proofs aberrance of serotonin signaling in the pathomechanism of schizophrenia, serotonin receptors, particularly 5-HT 3 and 5-HT 6 , still represent promising drug targets for the discovery of novel multi-receptors antipsychotic agents which can alleviate cognitive and negative symptoms of the disease [ 58 , 59 ].

Serotonin-receptor-based signaling was proposed to have an important role in the action of the atypical antipsychotics [ 60 ]. It was suggested by Meltzer et al. [ 61 ] that significant 5-HT 2A receptor antagonism accompanied by diminished dopamine D 2 receptor antagonism are the key pharmacological attributes which characterize clozapine and other second-generation antipsychotics and differentiate them from first-generation drugs. Several serotonin receptors, including 5-HT 2A / 2C , 5-HT 1A , 5-HT 6 and 5-HT 7 receptors, can be partially responsible for the “atypicality” [ 62 ]. Many studies demonstrated that partial and full 5-HT 1A receptor agonists can diminish antipsychotic-induced catalepsy. Consequently, certain second-generation drugs which display a balance between dopamine D 2 antagonism or partial agonism and 5-HT 1A receptor agonism/partial agonism result in low extrapyramidal side effects, which was demonstrated as low cataleptogenic activity in animal models [ 63 ]. Polymorphism of 5-HT 2C receptor gene is associated with olanzapine-induced weight gain [ 64 ]. Moreover, in meta-analyses, three genetic variants within serotonin genes were found linked to clozapine-associated weight gain: rs6313 and rs6314 within HTR2A gene and rs1062613 within HT3A gene [ 65 ]. Moreover, amisulpride, which has a high affinity for serotonin 5-HT 7 receptors, reversed ketamine-induced social withdrawal in rat models [ 66 ]. Next, the antagonism of 5-HT 7 receptors may be partially responsible for antidepressant and procognitive activity of amisulpride [ 67 ].

2.4. Other Aminergic GPCRs in Schizophrenia

Besides dopamine and serotonin receptors, other aminergic receptors are also linked to schizophrenia, i.e., histamine, muscarinic and adrenergic receptors. Histamine H 3 receptor antagonists can be useful in treating cognitive deficits of schizophrenia [ 68 ].

Muscarinic receptors have a key role in modulating synaptic plasticity in the prefrontal cortex and stimulation of these receptors results in long-term depression at the hippocampo-prefrontal cortex synapse [ 69 ]. Cholinergic neurotransmission is impaired in patients with schizophrenia and in animal models of schizophrenia [ 69 ]. Importantly, muscarinic receptor antagonists deteriorate cognitive and negative symptoms in schizophrenia patients and xanomeline, a muscarinic receptor agonist, ameliorates all symptoms in schizophrenia patients and corresponding animal models [ 69 ].

There are also reports that α adrenergic receptors activity can be crucial for aberrant regulation of cognition, arousal, and valence systems associated with schizophrenia [ 70 ].

2.5. GABAergic Hypothesis of Schizophrenia

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the CNS [ 71 ]. GABAergic interneurons are crucial for suppression of the CNS, key for the synchronization and oscillations of activity of neurons which are vital for perception, learning memory, and cognition [ 72 ]. GABA signaling disturbances cause imbalance between excitation and inhibition in the cerebral cortex which is one of the key factors in the pathomechanism of schizophrenia [ 73 , 74 ]. A role of GABA in schizophrenia was first noticed by Eugene Roberts in 1972 [ 75 ]. It was first suggested that GABA can be applied for the treatment of schizophrenia as it inhibits dopaminergic signaling, however recent evidence demonstrated that, in some models, GABA can have adverse effect on the dopamine activity [ 75 ].

Post-mortem studies supported the hypothesis about a changed GABA transmission in schizophrenia [ 72 ]. Importantly, the reduction of glutamic acid decarboxylase-67, GABA synthetic enzyme was observed in brain parts linked with critical cognitive functions (the dorsolateral prefrontal cortex, anterior cingulate cortex (ACC), motor cortex, visual cortex, and hippocampus) [ 72 ].

The decrease in transmission through the TrkB neurotrophin receptor results in a diminished GABA synthesis in parvalbumin-containing subpopulation of GABA neurons in the dorsolateral prefrontal cortex of schizophrenia patients. Despite both pro- and presynaptic compensative responses, the resulting change in the perisomatic inhibition of pyramidal neurons leads to a reduced capacity for the gamma-frequency synchronized neuronal functioning, which is necessary for the working memory functioning [ 76 ].

Changes in the GABA neurotransmission were found in basic and clinical research on schizophrenia and in animal models. The chandelier subtype of parvalbumin-positive GABA neurons can be particularly altered by, and characteristic for schizophrenia [ 77 ]. GABA interneurons are key to brain rhythm-generating networks, and synchrony of neural oscillations is crucial for the perception, memory and consciousness [ 78 ]. GABA signaling disturbances can result in changes in neural synchrony [ 78 ], abnormal gamma oscillations [ 79 ], and working memory deficits.

In clinical studies, the administration of GABA agonists was demonstrated to attenuate schizophrenia symptoms [ 80 ]. Nevertheless, it is not known how GABA interplays with other neurotransmitter systems which needs further investigation.

2.6. Nicotinic Receptors in Schizophrenia

Many people suffering from schizophrenia smoke. This can be attributed to the disease itself or its treatment [ 81 ]. There are numerous reports about disturbed brain cholinergic transmission in patients with schizophrenia [ 82 ]. Patients communicate that smoking helps them to relieve negative symptoms [ 83 , 84 ] which can be linked to their deficiencies regarding nicotinic receptors.

The high rate of smokers among patients with schizophrenia stimulated the research on the role of nicotinic receptors in this disorder [ 85 ]. Studying of α7 receptors with specific venomous toxins showed that α7 receptors are located in brain regions involved in cognition (e.g., the cortex and hippocampus) [ 85 ]. Deterioration of cognitive abilities such as working memory and cognitive flexibility, as well as attention, anticipate psychotic symptoms and are a prognosticator of functional outcome [ 85 ].

Preclinical and clinical research demonstrated that the diminished suppression of P50 auditory evoked potentials in schizophrenia patients can be linked with a lowered density of α7 nicotinic receptors in the CNS [ 86 ]. Schizophrenia patients display weak inhibition of P50-evoked responses to repeated auditory stimuli, which can result from damaged sensory gating. The influence of smoking, however, on the reversing of lowered auditory sensory gating in schizophrenia may be weakened as a result of the desensitization of the nicotine receptors. This was connected with the chromosome 15q14 locus of the α7 nicotinic receptor gene [ 87 ]. Consequently, nicotinic receptors can be an attractive drug target for the treatment of schizophrenia.

The results of trials with α7 nicotinic receptor agonists or positive allosteric modulators are promising [ 88 ] but require further investigation.

2.7. The Endocannabinoid System in Schizophrenia

The endocannabinoid system is changed in schizophrenia (i.e., elevated density of cannabinoid CB1 receptor binding in corticolimbic regions and increased levels of andamide in cerebrospinal fluid). This results in “cannabinoid hypothesis” of schizophrenia [ 89 ]. Moreover, certain genetic changes of the CNR1 gene may protect against schizophrenia or can promote a better pharmacological response to atypical antipsychotics [ 89 ].

2.8. Role of Inflammation and Oxidative Stress in the Pathomechanism of Schizophrenia

The role of inflammation and oxidative stress in schizophrenia is a focus of many studies [ 34 ]. It was reported that severe infections and immune disorders during the life-time are an additional risk factor for the development of schizophrenia [ 90 , 91 ]. Although prenatal infections alone do not seem to be a definitive risk factor, the neurodevelopmental exposure to infection can facilitate the occurrence of psychosis in offspring. This can be supported by the observation that during influenza epidemics women are more likely to give birth to children who develop schizophrenia [ 92 ]. In this regard, there are inflammatory models of psychotic disorders, e.g., the anti-NMDAR encephalitis syndrome [ 93 ]. In this disease, schizophrenia-liked symptoms are combined with elevated level of NMDA receptor autoantibodies. Immunotherapy is a treatment option for this syndrome. This is also indirect proof of involvement of glutamatergic system in the pathomechanism of schizophrenia.

Another treatable immune model of schizophrenia is gluten sensitivity with the occurrence of anti-tissue transglutaminase or anti-gliadin antibodies [ 94 ]. Indeed, there can be a possible relationship between diet rich in grain products with high gluten content and the occurrence or exacerbation of schizophrenia symptoms [ 95 ].

As a consequence of inflammation role in schizophrenia, antibiotics and anti-inflammatory agents have been tested to treat this disease but with a rather limited success [ 96 ]. However, a trial of 1000 mg per day of aspirin as add on treatment demonstrated improvements in the Positive and Negative Syndrome Scale (PANSS) total and positive symptoms [ 97 ].

The importance of oxidative stress in schizophrenia was suggested in the 1930s but it was for a long time underestimated. Recent studies indicate that the oxidative stress preferentially affects interneurons which can be subjected to antioxidant therapies [ 98 , 99 ]. Next, lipid-rich white matter is also sensitive to oxidative stress which can underlie myelin-associated deficiencies in schizophrenia [ 100 ].

3. Classical Approaches to Treat Schizophrenia

Due to poor understanding of the causes of schizophrenia, the treatment, engaging antipsychotic drugs, focuses mainly on reducing the symptoms of the disease. Although psychotic illnesses include a number of various disorders, the term antipsychotic drugs—also known as neuroleptics, major tranquillizers or anti-schizophrenic drugs—conventionally refers to drugs used to treat schizophrenia. The same drugs are also used to treat brain damage, mania, toxic delirium, agitated depression and other acute behavioral disturbances. In terms of pharmacology, most are antagonists of dopamine receptor, although many of them also have an affinity for other targets, especially serotonin receptors, which may have an impact on their clinical efficacy. Currently available drugs have many drawbacks when it comes to their efficacy and side effects. Even though gradual improvements with newer drugs have been achieved, radical new approaches require a deeper understanding of the pathomechanism and causes of the disorder that are still insufficiently understood [ 101 ].

The purpose of treatment is to reduce the suffering of the patient and to improve functioning in cognitive and social area. Life-long treatment with antipsychotic drugs is required in case of many patients. Neuroleptics relieve positive symptoms of schizophrenia such as thought disorder, delusions and hallucinations, and prevent relapse. Their effectiveness is lesser on negative symptoms, which include social withdrawal and apathy. In many patients, negative symptoms have a tendency to persist between periods of treated positive symptoms, but early begun treatment of schizophrenia may prevent the development of negative symptoms over time. Patients suffering from acute schizophrenia usually respond better to treatment than those with the symptoms of chronic disease. To prevent relapses, long-term treatment is usually necessary after the first episode of the disease. Doses that are effective in acute schizophrenia should ordinarily be continued as prophylaxis [ 102 ].

The clinical effectiveness of antipsychotics in enabling patients suffering from schizophrenia to lead relatively normal lives has been presented in many controlled trials. The patient population of psychiatric hospitals, which was comprised of mainly chronic schizophrenics, declined exponentially in the 1950s and 1960s. It took place due to the introduction of neuroleptics, as well as the changing professional and public attitudes in terms of hospitalization of mentally ill patients. However, antipsychotic drugs suffer severe limitations which include:

- (1) Some patients lack response to drug treatment. Clozapine is recommended in patients resistant to other neuroleptics. The 30% of patients that do not respond are classified as “treatment resistant” and represent a major problem regarding treatment. It is still unknown what underlies the difference between responsive and unresponsive patients, although there are some presumptions that polymorphisms within the dopamine and serotonin receptors family may be involved.
- (2) They are effective in relieving the positive symptoms (delusions, hallucinations, thought disorders, etc.) but most of them lack effectiveness in controlling the negative symptoms (social isolation, emotional flattening) and cognitive dysfunctions.
- (3) They may result in a wide range of side effects including extrapyramidal, sedative and endocrine effects that can limit patient compliance.
- (4) They may decline survival through pro-arrhythmic effects.

Antipsychotic drugs of second generation were believed to overcome these limitations to some degree. However, according to meta-analysis performed by Leucht and co-workers [ 103 ], only some of the examined second-generation neuroleptics, displayed better overall efficacy. Sudden cessation of administration of antipsychotic drugs may result in a rapid onset of psychotic episode, that are different from the underlying illness [ 101 ].

The antagonism of dopamine D 2 receptors located in the mesolimbic pathway is believed to reduce the positive symptoms of schizophrenia. Unluckily, systemically administered neuroleptics do not distinguish between D 2 receptors in different brain areas and thus D 2 receptors present in other regions of the central nervous system will be blocked as well. As a result of this effect, antipsychotics lead to unwanted motor effects (blocking D 2 receptors in the nigrostriatal pathway), enhanced secretion of prolactin (blocking D 2 receptors in the tuberoinfundibular pathway), reduced pleasure (blocking D 2 receptors in the reward system component in the mesolimbic pathway) and presumably they even exacerbate the negative symptoms of the disease (blocking D 2 receptors located in the prefrontal cortex, although they occur in low abundance–D 1 receptors are expressed at higher density). While all neuroleptics, excluding third generation, act by blocking D 2 receptors and therefore, theoretically, should induce all of these side effects, some exhibit additional pharmacological activity (e.g., antagonism at muscarinic and 5-HT 2A receptor) that, to various degree, reduce unwanted effects. Blockade of 5-HT 2A receptor may also contribute to alleviating the negative and cognitive symptoms of schizophrenia [ 101 ].

The concept that serotonin dysfunction can be involved in the development of schizophrenia has come in and out of favor several times. As already mentioned, originally, it was based on the fact that LSD, which is a 5-HT 2A receptors partial agonist, produces hallucinations. However, nowadays, it is thought that serotonin is not directly associated with the pathogenesis of schizophrenia. Nonetheless, affecting serotonin receptors, combined with antagonism at D 2 receptor, has resulted in development of new drugs with improved pharmacological and therapeutic profiles. These are serotonin 5-HT 2A and 5-HT 1A receptors that play an important role in the treatment of schizophrenia.

5-HT 2A receptors belong to G i /G o -coupled receptors and, being activated, produce neuronal inhibition. In the nigrostriatal pathway, 5-HT 2A receptors control the dopamine release in this way. Drugs that are antagonists to 5-HT 2A (e.g., olanzapine, risperidone) enhance the release of dopamine in the striatum by decreasing the inhibitory effect of serotonin. It will manifest in reducing extrapyramidal side effects. Moreover, in the mesolimbic pathway, combined effects of antagonism at D 2 and 5-HT 2A receptors are suggested to counteract the enhanced dopamine function that cause positive symptoms of schizophrenia. Furthermore, block of 5-HT 2A receptor appears to improve the negative symptoms on account of enhancing the release of both dopamine and glutamate in the mesocortical circuit. 5-HT 1A receptors, which are somatodendritic autoreceptors, inhibit serotonin release. Neuroleptics that are 5-HT 1A receptors agonists or partial agonists (e.g., quetiapine) may act by reducing the release of serotonin and thus increasing dopamine release in prefrontal cortex and the striatum.

Some phenothiazine antipsychotics (e.g., periyazine) have been proven to cause fewer extrapyramidal effects than others, which is thought to be correlated with their antagonist properties to muscarinic receptors. Some second-generation drugs (e.g., olanzapine) also exhibit muscarinic antagonist properties. Dopaminergic nerve terminals in the striatum are suggested to innervate cholinergic interneurons which express inhibitory D 2 receptors [ 104 ]. Normally, there is an equilibrium between activation of dopamine D 2 and muscarinic receptor. Antipsychotic drug that block D 2 receptors in the striatum will lead to increased release of acetylcholine on to muscarinic receptors, producing extrapyramidal side effects, which are neutralized if the antagonist of D 2 receptor also display antagonist activity at muscarinic receptors. Maintaining the balance between dopamine and acetylcholine was also the rationale behind the use of benztropine, the muscarinic antagonist, to reduce extrapyramidal side effects of neuroleptics. However, antagonist activity at muscarinic receptors may result in side effects such as blurred vision, dry mouth and constipation [ 101 ].

The term “atypical” is widely used, although it has not been clearly defined. In result, it refers to the diminished tendency of later drugs to cause motor side effects, but it is also used in describing compounds that have different pharmacological profile from first-generation antipsychotics. In practice, it frequently serves—not very usefully—to distinguish the large group of similar first-generation dopamine antagonists from the group of later compounds, which is characterized by higher degree of diversity. Distinction between first- and second-generation antipsychotic drugs rests on such criteria as: receptor profile, occurrence of extrapyramidal side effects (less in second-generation group), efficacy (especially of clozapine) in resistant to treatment group of patients, and efficacy against negative symptoms [ 101 ].

It is also worth mentioning that nowadays new system of nomenclature for psychotropic medications that is neuroscience-based nomenclature (and its further update neuroscience-based nomenclature-2) is recommended [ 105 ]. This system supplies a pharmacological driven nomenclature which focuses on pharmacology and mode of action, reflecting available knowledge and understanding about the targeted neurotransmitter, molecule, system being modified, and mode/mechanism of action. It also includes four additional dimensions: (1) approved indications; (2) efficacy and side effects; (3) “practical note” which summarizes the clinical knowledge that has been prioritized by “filtering” though the taskforce’s “opinion sieve”; and (4) neurobiology.

3.1. First-Generation Antipsychotics

The first-generation antipsychotic drugs act mainly by blocking dopamine D 2 receptors in the brain. They do not exhibit a selectivity for any of the dopamine pathways in the central nervous system and therefore can lead to a range of side-effects, in particular extrapyramidal symptoms and elevated prolactin. In this and the following sections, the most common adverse effect of antipsychotics are mentioned.

The history of antipsychotic drugs dates to December 1950, when chlorpromazine, the first neuroleptic that belongs to the family of phenothiazines, was synthesized in France by the chemist Paul Charpentier as a result of research on new antihistaminic drugs. Further behavioral experiments confirmed antipsychotic properties of chlorpromazine. The release of chlorpromazine to the market took place in 1953 with the trade name Largactil , which derives from “arge” and “acti”, indicating the broad activity of the drug [ 106 ].

According to chemical structure the first-generation antipsychotics may be divided into several groups, as showed in Table 1 [ 107 ].

Classification of first-generation antipsychotic drugs: examples and their chemical structures.

The prototypical and the largest group of antipsychotic drugs in terms of chemical structure is the group of phenothiazines. It may be divided into three subclasses, which comprise in total more than forty drugs. All of them share three-ring phenothiazine structure but differ with side chains joined to the nitrogen atom (position 10 of phenothiazine) and substituents in position 2, which affects the activity of the drug. The three subgroups of phenothiazines have been distinguished considering the side chain in position 10. They are aliphatic, piperidine, and piperazine phenothiazines. The potency of drugs depends on their side chain and therefore aliphatic and piperidine phenothiazines may be characterized as agents of low to medium potency, whereas the potency of piperazine phenothiazines is described as medium to high [ 108 ].

Aliphatic group of phenothiazine derivatives is generally characterized by explicit sedative effects and moderate extrapyramidal and antimuscarinic side effects. Piperidine phenothiazines have moderate sedative effects, but cause fewer extrapyramidal side effects than other groups. Drugs with side chain containing piperazine exhibit fewer sedative and antimuscarinic effects, but more pronounced extrapyramidal side effects than in case of aliphatic and piperidine phenothiazines [ 102 ].

Another group of typical antipsychotic drugs are butyrophenones (e.g., benperidol, droperidol, and haloperidol) whose pharmacological properties are similar to those of piperazine phenothiazines, although their antidopaminergic effect is probably higher than in the case of phenothiazines, with lower antihistaminic, antiadrenergic and anticholinergic effect. Thioxanthenes exhibit moderate sedative, extrapyramidal and antimuscarinic effects, whereas diphenylbutylpiperidines are characterized by reduced sedative, antimuscarinic and extrapyramidal effects [ 108 ].

The relative potency of typical antipsychotics can be expressed by comparison with chlorpromazine and according to that first-generation neuroleptics can be arranged from low to high potency. The measure of “chlorpromazine equivalence” defines the amount of the drug in mg which allows to achieve the same effect as administration of 100 mg of chlorpromazine. The examples of high potent antipsychotic drugs are haloperidol and fluphenazine, both with chlorpromazine equivalent dose of 2 mg. Thioridazine is an antipsychotic of low potency, according to this classification, and is comparable with chlorpromazine—it must be administered in the dose of 100 mg to achieve similar potency as 100 mg of chlorpromazine [ 101 , 108 ].

Due to affecting wide range of receptors and lack of selectivity to dopamine receptors located in the mesolimbic pathway, antipsychotic drugs result in numerous side effects. The most frequent and severe are extrapyramidal effects, such as dyskinesia, dystonias, akathisia, unwanted movements, muscle breakdown, tremors and rigidity, which occur as a result of blocking dopamine D 2 receptors in the nigrostriatal pathway. High doses of typical antipsychotics may induce negative and cognitive symptoms by antagonism to dopamine receptors in the mesocortical pathway, whereas blocking those receptors in the tuberoinfundibular pathway increases the release of prolactin in the pituitary gland and leads to hyperprolactinemia. Another side effects on the CNS are sedation (resulting from antihistaminic activity), drowsiness, vertigo, disturbed sleep, agitation, nightmares, dementia, loss of memory, and depression. Blockade of α 1 adrenergic receptors may cause hypotension. Side effects on cardiovascular system comprise also tachycardia, palpitation, arrhythmia or chest pain. Antipsychotic drugs affect also liver. They increase the concentration of alkaline aminotransferase in the serum and may cause side effects such as jaundice, reversible liver cell hyperplasia, necrosis and increased level of bilirubin. Some effects from the side of the urinary and reproductive system have also been reported: impotence, increased or decreased libido, priapism, polyuria, delayed and premature ejaculation, galactorrhea and anorgasmia. Side effects related to the gastrointestinal system, such as weight gain, nausea, dry mouth, heartburn, anorexia, epigastric distress, dyspepsia, constipation, increased level of pancreatic enzymes, and abdominal cramps, are also common. Other adverse reactions that may result from the treatment with antipsychotic drugs involve: hot flashes, nasal congestion, numbness, blurred vision, dry throat, neutropenia, leukopenia, agranulocytosis, chills, glaucoma, hyperlipidemia, and depression of the respiratory system [ 101 , 108 ].

3.2. Second-Generation Antipsychotics

The new era in treating schizophrenia has begun when, after almost forty years from the introduction of chlorpromazine, the first antipsychotic, FDA approved the clinical use of clozapine in the cases of treatment-resistant schizophrenia. Clozapine has been synthesized in the laboratories of Sandoz and, after clinical trials were performed, released to the market in such countries as Switzerland, Austria, West Germany and Finland. However, studies on clozapine performed at the same time in the USA resulted in reports of agranulocytosis leading to death in some patients treated with the drug. Thus, clozapine disappeared from the market for a long time, but the interest of the scientists in working on the drug did not diminish. Further studies proved the high efficacy of clozapine in the treatment-resistant forms of schizophrenia, which resulted in the FDA approval for the drug in this disease entity [ 109 ].

Clozapine was the first drug with a stronger ability to reduce negative symptoms and that causes fewer extrapyramidal symptoms than known to date antipsychotics. The discovery of clozapine contributed to the introduction of new drugs with more beneficial pharmacological profile than first generation antipsychotics. Generally, second=generation drugs, in comparison with classical antipsychotics, exhibit higher ability to block serotonin 5-HT 2A receptors than dopamine D 2 receptors. Additionally, antagonism to D 2 receptors is weaker in the case of second-generation antipsychotics comparing to those of first generation, which manifests in lower occurrence of extrapyramidal side effects. There are also hypotheses that suggest that atypical antipsychotics bind to dopamine receptors with high dissociation rates or that they are more likely to block dopamine receptors in cortical and limbic regions than in nigrostriatal pathway, which also contributes to lower risk of extrapyramidal effects [ 110 ].

Besides schizophrenia, atypical antipsychotics are used in other diseases, such as bipolar disorder, anxiety disorder, obsessive-compulsive disorder, agitation associated with dementia and autism spectrum disorder [ 111 ]. This makes searching for novel antipsychotics even more important as there is a significant group of patients who need antipsychotics on a daily basis. Second-generation antipsychotics currently approved for clinical use include: clozapine, olanzapine, quetiapine, risperidone, paliperidone, ziprasidone, and molindone ( Figure 1 ).

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The chemical structures of representatives of second-generation antipsychotic drugs.

Clozapine, as an atypical antipsychotic, is dopamine and serotonin receptor antagonist. It binds to dopamine D 1–5 receptors, with ten times higher affinity to D 4 receptors than to D 2 . Both D 4 and 5-HT 2A antagonist properties contributes to decrease of negative symptoms and lower occurrence of extrapyramidal side effects. The effect of clozapine on 5-HT 2A receptor signaling differs from classic GPCR antagonists, as it also induces 5-HT 2A receptor internalization and activates Akt signaling via a 5-HT 2A receptor-mediated event [ 112 ]. Thus, clozapine may also be considered a functionally selective agonist. At this serotonin receptor, clozapine is also serotonin 5-HT 1A receptor partial agonist, which is thought to have beneficial effect in terms of reducing negative and cognitive symptoms. Muscarinic receptors are also affected by clozapine: it blocks M 1 , M 2 , M 3 and M 5 receptors, while stimulates M 4 receptor (which results in an excessive salivation as a side effect). Clozapine’s metabolite norclozapine is an allosteric modulator of muscarinic M1 and M4 receptors [ 50 ]. The use of clozapine is associated also with sedation, as a result of antagonism to histamine receptors, and side effects from autonomous system, including hypotension and reflex tachycardia, which in turn result from blockade of α 1 adrenergic receptors. Clozapine is currently used mainly in forms of schizophrenia that are resistant to treatment with other drugs, which means that no satisfactory response has been achieved with at least two other drugs. The main limitation of clozapine is its tendency to cause agranulocytosis, which may lead to death. FDA suggests patients to control the number of white blood cells every week during first six months of treatment (it is the period of the highest risk of agranulocytosis). Afterwards, the number of leukocytes should be controlled every two weeks [ 108 ].

Olanzapine is a chemical analog of clozapine with similar pharmacological properties. However, contrary to clozapine, olanzapine causes fewer autonomic side effects and its use is not associated with a risk of agranulocytosis. Affinity of olanzapine to serotonin 5-HT 2 receptors is approximately two times higher than to dopamine D 2 receptors. It also blocks D 3 and D 4 receptors. Antagonism to histamine, muscarinic and α 1 -adrenoreceptors is weaker than in the case of clozapine. Clinical trials showed that efficacy of olanzapine in reducing positive symptoms is comparable with haloperidol, but is much more effective against negative symptoms and causes fewer side effects than haloperidol. The most frequent side effects of olanzapine are sedation and weight gain.

Quetiapine belongs to antipsychotics, which, besides schizophrenia, are used in treating bipolar disorders and major depressive disorders. Its off-label application includes insomnia, Tourette syndrome or anxiety disorders. Quetiapine acts as a dopamine D 1 , dopamine D 2 and serotonin 5-HT 2 receptors antagonist. Quetiapine is also a 5HT 1a receptor partial agonist. Antagonism to α 1 adrenergic and histamine H 1 receptor manifests in occurrence of side effects such as sedation and orthostatic hypotension.

Risperidone is the first novel atypical antipsychotic. It was introduced to the market at the beginning of the 1990s, twenty years after introduction of clozapine [ 113 ]. It is a benzisoxazole derivative ( Figure 1 ). Its pharmacological profile is reminiscent of properties of olanzapine, except that risperidone is thought to cause sedation less frequent and orthostatic hypotension more often than olanzapine. Therapeutic effect of risperidone results from antagonism to both D 2 and 5-HT 2A receptors with 5-HT 2A antagonism significantly stronger than the D 2 antagonism. Moreover, this drug also causes α 1 adrenergic and histamine receptor blockade. Its anticholinergic effects are negligible. In some patients, risperidone may elevate the level of prolactin and cause arrhythmia. The following other adverse effects may occur during treatment with risperidone: insomnia, restlessness, anxiety, headaches, agitation, EPS, headache, rhinitis, sedation, somnia, fatigue, ocular disturbances, orthostatic dizziness, palpitations, weight gain, diminished sexual desire, erectile and ejaculatory dysfunction, orthostatic dysregulation, reflex tachycardia, gastrointestinal complaints, nausea, rash, galactorrhea and amenorrhea [ 113 , 114 ]. Risperidone is efficient not only in treating positive symptoms but also negative and cognitive disturbances as well as has some anti-depressant properties which makes it one of the most commonly prescribed antipsychotics [ 113 ]. The active metabolite of risperidone is paliperidone, which acts on the same range of receptors. It is used in treating schizophrenia, as well as mania and, in lower doses, in bipolar disorder. Paliperidone comes in formulations of extended release, what allows to administer the drug once per day [ 108 ].

Ziprasidone, another second-generation antipsychotic, acts as antagonist of dopamine D 2 and serotonin 5-HT 2A receptors, partial agonist of 5-HT 1A receptor, and partial antagonist of 5-HT 2C and 5-HT 1D receptors. Besides schizophrenia it is used in acute mania or bipolar disorders [ 115 ].

Molindone acts mainly by affecting dopamine transmission in the brain. It is an atypical antipsychotic with unusual profile of pharmacological properties. It rarely causes sedation and autonomic side effects but is thought to lead to extrapyramidal side effects more frequent than other new antipsychotics, although still less frequently than classical neuroleptics. The use of molindone, contrary to other second-generation antipsychotics, rarely results in weight gain. In patients that do not tolerate or respond to other drugs, the treatment with molindone is sometimes effective [ 108 ].

Other second-generation antipsychotics include: lurasidone, iloperidone, asenapine, sertindole and amisulpiride. They are briefly presented below.

Lurasidone is a benzisothiazole derivative with high antagonist activity at serotonin 5-HT 2A and 5-HT 7 receptors and weaker antagonism at dopamine D 2 receptor [ 116 ]. It is also a partial agonist of serotonin 5-HT 1A receptor and has relatively high affinity adrebergic α 2A and weaker affinity to muscarinic receptors [ 116 ]. In general, lurasidone is effective and well-tolerated for treatment of schizophrenia and for acute bipolar depression. It has low probability of side effects such as weight-gain, and metabolic or cardiac abnormalities, but higher risk of akathisia in comparison to other atypicals [ 116 ].

Iloperidone is a benzoxazole derivative with high affinity to serotonin 5-HT 2A and dopamine D 2 receptors [ 117 ]. Iloperidone has also high affinity to α 1 adrenergic receptors and lower affinity to dopamine D 1 receptors, serotonin 5-HT 1A receptors and histamine H 1 receptors and negligible affinity to muscarinic receptors [ 117 ]. This drug has beneficial EPS and akathisia properties which makes it attractive choice for patients whose compliance is limited by these effects [ 117 ].

Asenapine is a dibenzoxepinopyrrole derivative and has a high affinity for the serotonin 5-HT 2A receptor and to a lesser extent to dopamine D 2 receptor [ 118 ] It is an antagonist of 5-HT 2C , H 1 and α2-receptors. It shares a rather complex binding profile with clozapine, olanzapine and quetiapine. The main side effects of asenapine are weight gain and metabolic disorders [ 119 ].

Sertindole is an indole derivative with a high affinity for dopamine D 2 , serotonin 5-HT 2A and 5-HT 2C , and α 1 adrenergic receptors [ 120 ]. It has also some affinity for histamine H 1 and muscarinic receptors. This drug has low probability to cause sedation and EPS and displays an acceptable metabolic profile. However, cardiac safety should be monitored during treatment with sertindole.

Amisulpiride belongs to benzamides and is a specific antagonist for dopamine D 2 and D3 receptors [ 121 ]. It has negligible affinity to serotonin receptors and receptors typically involved in side effects of atypical antipsychotics. EPS is the most common side effect of amisulpiride.

In the past decade, first-generation antipsychotics have been essentially replaced by newer, atypical antipsychotics mainly due to better toleration of second-generation antipsychotics and their more favorable profile of side effects, especially lower risk of extrapyramidal side effects. However, the second-generation antipsychotics have severe metabolic adverse effects, in particular obesity and diabetes. Weight gain and metabolic disfunctions are common in schizophrenia patients. It is attributed to the blockade of adrenergic, cholinergic, and histaminergic postsynaptic receptors by psychotropic agents [ 122 ]. Indeed, antagonism of histamine H 1 receptors is described as a key reason of second-generation antipsychotics-induced obesity [ 123 ]. Moreover, sedation, a common side effect of clozapine treatment, can be connected with clozapine binding to histamine receptors in the CNS [ 124 ]. Type 2 diabetes mellitus is their most often reported output [ 125 ]. Metabolic side effects are mainly associated with clozapine and olanzapine while data are mixed for risperidone and quetiapine [ 125 ]. For other second-generation antipsychotics, there are only few studies which examined their metabolic effects so it is difficult to draw conclusions [ 125 ].

3.3. Third-Generation Antipsychotics

The newest group of antipsychotic drugs, described as the third generation, consists of aripiprazole, brexpiprazole and cariprazine ( Figure 2 ). That group has been individualized on the grounds of their mechanism of action on dopamine receptors. Unlike other neuroleptics, third-generation drugs are not dopamine D 2 receptor antagonists but D 2 partial agonists. The D 2 receptor partial agonist properties of aripiprazole concern inhibition of cAMP accumulation through the dopamine D 2 receptor (i.e., G α signaling) [ 126 , 127 ] and in the presence of high extracellular concentrations of dopamine (e.g., in mesolimbic areas), compete with dopamine and result in partial antagonism leading to clinical benefits. Contrarily, when extracellular dopamine concentration is on a low level (e.g., in dopamine circuits that are involved in working memory), aripiprazole can bind to additional receptors and activate them partially. Hence, aripiprazole is termed as “dopamine stabilizer” [ 128 , 129 , 130 ]. It has also been demonstrated that aripiprazole is an antagonist in GTPγS binding assays with dopamine D 2 receptor [ 127 , 131 ]. Aripiprazole also failed to activate outward potassium currents following activation of dopamine D 2 receptor, which can indicate that it was inactive or an antagonist for Gβγ signaling through this receptor [ 127 ]. Next, aripiprazole, as another clinically efficient antipsychotic, is an antagonist of β-arrestin pathway [ 132 ]. Moreover, aripiprazole was also reported as agonist or antagonist of other GPCRs [ 133 ]. When it comes to serotonin transmission, aripiprazole exhibits partial agonistic properties to 5-HT 1A and 5-HT 2A (much weaker in the second case), which manifests in functional antagonism at this receptor. Contrary to antipsychotic drugs classified as second generation, aripiprazole displays higher affinity for dopamine D 2 receptor than for serotonin 5-HT 2A receptor. Clinical use of aripiprazole includes, besides schizophrenia, bipolar disorder, major depression, obsessive-compulsive disorder, and autism. Effectiveness of treating schizophrenia with aripiprazole is comparable with haloperidol or quetiapine and slightly higher than in the case of chlorpromazine or ziprasidone. Moreover, aripiprazole is characterized by better tolerability comparing to other antipsychotics [ 134 ]. Side effects that may result from treatment with aripiprazole include mainly akathisia [ 135 ] but also weight gain, agitation, insomnia, anxiety, headache, constipation or nausea [ 129 ]. However, aripiprazole results in considerably lower weight gain and lower increase in glucose and cholesterol levels in comparison to clozapine, risperidone, and olanzapine [ 136 ]. Next, aripiprazole led to weaker EPS, less use of antiparkinsonian drugs, and less akathisia, in relation to typical antipsychotic drugs and risperidone [ 136 ].

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02087-g002.jpg

Antipsychotic drugs categorized as the third generation and their structures.

Brexpiprazole, approved by FDA in 2015, acts as partial agonist to dopamine D 2 , D 3 and serotonin 5-HT 1A receptors, and exhibits also antagonist properties to 5-HT 2A , 5-HT 2B and 5-HT 7 receptors. Its pharmacological profile is very similar to that of aripiprazole. Brexpirazole and aripiprazle are considerably different in potencies at many receptors. Their antipsychotic efficacy is comparable but brexpiprazole causes less akathisia, EPS and activation [ 137 ]. Moreover, brexpiprazole has precognitive properties [ 138 ] in contrast to aripiprazole [ 139 ]. Brexpiprazole, alone or in combination with escitalopram, facilitates prefrontal glutamatergic transmission via a dopamine D 1 receptor-dependent mechanism [ 140 ]. The drug is used in the treatment of schizophrenia and as an adjunct in major depressive disorder (e.g., in combination with fluoxentine [ 141 , 142 ]). The side effects that may result from using brexpiprazol include akathisia, weight gain, infections of upper respiratory tract, somnolence, headache and nasopharyngitis [ 143 ].

Approval of cariprazine, as well as brexpiprazole, took place in 2015. Similar to other antipsychotics from third generation, cariprazine is dopamine D 2 , D 3 and serotonin 5-HT 1A receptors partial agonist. However, its affinity for dopamine D 3 receptor is approximately ten times higher than for D 2 receptors. Cariprazine can be considered a biased agonist at dopamine receptors, with antagonist or partial agonist activity depending on the signaling pathways linked to D 2 /D 3 receptors [ 144 ]. Mean half-life for cariprazine is 2–5 days over a dose range of 1.5–12.5 mg [ 145 ]. Cariprazine has two clinically significant metabolites, desmethyl-cariprazine and didesmethyl-cariprazine, the latter having a longer half-life than cariprazine [ 145 ]. The clinical use of cariprazine includes schizophrenia and manic or mixed episodes associated with bipolar disorder. In particular, cariprazine can be used for the treatment of schizophrenia patients with dominant negative symptoms, a typically difficult to treat group of patients [ 146 ]. The treatment with cariprazine may lead to occurrence of side effects, such as sedation, akathisia, weight gain, nausea, constipation, anxiety, and dizziness [ 147 ]. Metabolic side effects of cariprazine are however negligible [ 148 ]. In summary, a potential for treatment negative symptoms, anti-abuse potential, and a long half-life make cariprazine a promising drug against schizophrenia [ 149 ].

Introduction of newer antipsychotic drugs to the clinical practice has contributed chiefly to lowering extrapyramidal side effects. Patients are less likely to suffer from akathisia, dystonias, parkinsonian symptoms or tardive dyskinesia than in the case of treatment with first generation antipsychotics. However, advantage of atypical over typical drugs when it comes to effectiveness is still discussed. Some patients respond better to newer antipsychotics and in others older drugs are more effective. This issue requires further research, which is problematic, considering schizophrenia as a chronic disease and the fact that the percentage of hospitalization of schizophrenic patients is low. It should be stressed, however, that novel compounds acting on dopaminergic system are still under investigation for the treatment of schizophrenia. Compounds such as BL 1020, ITI-007, and JNJ-37822681 have been thoroughly studied, and compounds such as L-THP, Lu AF35700, S33138, and SB-773812 are under vigorous investigation [ 150 ].

4. Targeting Novel GPCR Signaling Mechanisms in Schizophrenia

4.1. gpcrs and their novel signaling mechanisms as drug targets.

According to the classical ternary complex model, the signaling through GPCRs can be illustrated as the coaction of three main players: a receptor, an agonist and a G protein. However, more and more experimental and computational studies support the view that GPCR functioning can be much more complex than depicted by the ternary complex model.

The discovery that a specific receptor can couple to more than one G protein type and, besides that, that GPCRs could trigger G protein-independent pathways, stimulated a more nuanced characterization of GPCR ligands. Indeed, there are ligands termed biased agonists that are capable of preferentially activating one receptor-associated pathway over another [ 151 ]. This has been connected with the existence of multiple receptor states, with different propensities to couple to G proteins or other signaling partners, and which can be differentially affected by functionally selected ligands. This complex receptor modulation, which has been termed functional selectivity [ 10 , 11 ], has opened a new avenue for the interrogation of specific GPCR-activated pathways and their impact on health and disease, as well as for the subsequent detection of pathway-selective drugs with a refined mechanism of action [ 152 ]. Characterization of the significance of particular pathways associated with a given receptor can provide insight into the optimal functional selectivity profile for the treatment of a particular disease. In particular, targeting β-arrestin signaling pathways can be promising in the case of antipsychotics (see below), however it should be avoided in the case of many other drugs, e.g., antinociceptive compounds targeting the µ opioid receptor [ 153 ].

At present, another hot topic in GPCR-oriented drug discovery is the design of allosteric modulators instead of orthosteric ligands [ 154 ]. Allosteric ligands possess the ability to modulate GPCR function by binding to receptor regions away from the orthosteric binding site. Allosteric modulators usually bind to receptor areas with a low degree of conservation between GPCR subtypes [ 155 ]. This binding specificity could also be the basis for the design of more selective drugs. Additionally, the fact that allosteric modulators can function together with ligands interacting at the orthosteric binding site makes drugs exploiting this phenomenon especially useful when treatment can be achieved by enhancing or decreasing an endogenous signal. Such an approach may make it possible to solve the problem of drug dependence, overdose risk and other adverse effects linked with classical orthosteric drugs. The allosteric mode of action brings several advantages, e.g., a ceiling effect preventing overdosing, high receptor selectivity, and even activation pathway selectivity which may in consequence lead to safer and more efficient drugs [ 15 ].

In addition, the growing body of experimental (cross-linking experiments, BRET and FRET studies) and computational (coarse-grained molecular dynamics simulations) reports suggesting negative and positive cooperativity between receptors, has paved the way to the concept that GPCRs can oligomerize [ 19 , 20 ]. Both homo- and heterodimerization was reported for numerous GPCRs and the resulting protein complexes were in some cases linked to particular functional outcomes. Thus, GPCR dimers, oligomers and receptor mosaics are now considered promising drug targets, which, due to their restricted tissue distribution, can result in tissue-specific drugs. Despite a growing number of functional interactions between dimers, drug discovery targeting GPCR complexes remains a challenge. Thus, a better description of the structural aspects of GPCR oligomerization and of its effect on signaling, accompanied by the developing of original treatment strategies, seems essential for further exploration of this mechanism of GPCR signaling [ 156 ].

4.2. Targeting GPCR Signaling Complexity in Schizophrenia

The GPCR signaling mechanisms described above have been considered as potential drug targets for novel antipsychotics. The most commonly exploited approach is intentional ligand promiscuity for multi-target drugs typical for second- and, to a lesser extent, first-generation antipsychotics which requires separation of the drug targets from the off-targets [ 157 ]. The treatment of complex diseases, such as Alzheimer’s disease, Parkinson’s disease, cancer or schizophrenia, which involve multiple receptors and enzymes in their pathomechanisms, require looking for potential drugs which satisfy the criteria of many pharmacophores, oppositely to acting on a single molecular target. It should be emphasized in schizophrenia and other complex psychiatric disorders, selective single-target drugs have a very limited efficacy. Clozapine with a nanomolar affinity to several aminergic GPCRs is efficient against drug-resistant schizophrenia and reflects the molecular pathomechanism of this disease, involving cross-talk of many neurotransmitter systems (in particular, dopaminergic, serotonergic, adrenergic and glutamatergic). The new paradigm in medicinal chemistry is to look for substances that act on several molecular targets simultaneously. To accomplish that, it is essential to find structural features which combine important classes of drug targets, leading to molecules with desired selectivity profiles. Although recently implement antipsychotics (e.g., cariprazine and brexpiprazole) are the third-generation drugs, efforts are still made to design new multi-target ligands which can be developed into second generation antipsychotics [ 29 , 158 ].

The next approach that is currently under extensive investigation is biased signaling and functional selectivity. D 2 receptors couple to Gα i/o subunits, which leads to a number of signaling events through the release/rearrangement of G proteins, involving inhibition/sensitization of adenylyl cyclase, G βγ potentiation of AC2, and ERK activation as well as β-arrestin pathway [ 159 , 160 ]. Latest reports allow concluding that selective modulation of signaling pathways downstream of the D 2 receptor can lead to development of more efficient and safer antipsychotics [ 161 ]. In particular, blockade of β-arrestin pathway can be considered a common feature of antipsychotics that exhibit either antagonist or partial agonist activity through Gα i/o -cAMP pathways [ 161 ]. This supposes that β-arrestin-biased D 2 antagonists can display unique antipsychotic profiles [ 161 ]. Contrary to that, a study with analogs of aripiprazole concluded that D 2 ligands with Gα i/o antagonist and β-arrestin agonist activity can display antipsychotic properties with diminished extrapyramidal side effects in animal model [ 7 ]. Several series of biased D 2 agonists have been reported [ 7 , 162 , 163 ] as underlying ligand and receptor structural features necessary for biased signaling. Moreover, as has already been mentioned, serotonin 5-HT 2A receptor functional selectivity can be important for the activity of antipsychotics as it was reported for clozapine [ 112 , 164 ].

Allosteric modulation of D 2 receptor as a mechanism for novel antipsychotics has been not sufficiently studied. Only a peptidomimetic PAOPA ( Figure 3 ), a positive allosteric modulator of D 2 receptor, has been proven to be successful in animal models of schizophrenia. Few negative allosteric modulators are known, e.g. SB269,652, homocysteine and analogs, see Figure 3 and their antipsychotic potential needs to be evaluated. A clear finding of antagonist allosteric actions on D 2 receptor has been demonstrated for homocysteine and analogs, which supports the possibility that homocysteine analogs can be developed into an efficient antipsychotic drug, since they reduce in vitro dopamine binding. Allosteric compound SB269,652 seems to act on D 2 receptor dimer [ 165 ], similarly as bivalent D 2 receptor ligands based on agonist or antagonist structures [ 166 , 167 ], which are however not drug-like due to their high molecular weight and are pharmacological tools rather than potential drugs. At present, no dimer-specific monovalent ligands are known for D2 receptor homodimers or heterodimers of this receptor and no ligands inducing or disrupting dimerization are known.

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02087-g003.jpg

Allosteric modulators of dopamine D 2 receptor with possible application for the treatment of schizophrenia.

In addition to allosteric modulators of dopamine D 2 receptor, positive allosteric modulators of metabotropic glutamate receptors are nowadays studied as possible treatment for schizophrenia [ 168 ]. In particular, PAMs of mGluR1, mGluR2, mGluR3 and mGluR5 are promising. Furthermore, PAMs of muscarinic receptors, e.g., M 1 and M 4 receptor could be also useful [ 168 ].

Targeting D 2 -receptor-containing dimers is a new and yet unexploited strategy for the treatment of schizophrenia. Among heterodimers formed by the D 2 receptor, adenosine A 2A –D 2 and serotonin 5-HT 2A –D 2 heterodimers in particular are implicated in the pathomechanism of schizophrenia [ 169 ]. A possible biochemical alteration in schizophrenia might not only be D 2 receptor sensitization with elevated D 2 receptor signaling, but also decreased A 2A receptor activity or interruption of A 2A –D 2 receptor interactions because of the existence of abnormal A 2A –D 2 receptor heteromers or by their disappearance [ 170 ]. Observations supporting the presence of A 2A –D 2 heteromers with antagonistic A 2A –D 2 interactions in the ventral striatopallidal GABA pathway suggested the use of A 2A receptor agonists as a strategy for the treatment of schizophrenia [ 171 ]. The antipsychotic potential of A 2A receptor agonists is underlined through behavioral analysis in animal models of schizophrenia in which they demonstrated an atypical antipsychotic profile [ 171 ]. Other classes of potential antipsychotics acting through the A 2A –D 2 receptor heteromer may be the heteromer selective D 2 receptor orthosteric or allosteric antagonists or compounds promoting ligand-induced dimerization. The possible involvement of the D 2 –5-HT 2A heterodimer in schizophrenia was proposed by studies on the hallucinogenic 5-HT 2A agonists showing that they probably induce a conformational state of the 5HT 2A protomer different from the one produced by serotonin, leading to facilitating allosteric interactions with the D 2 partner [ 171 ]. This increase in the D 2 receptor signaling in the D 2 –5-HT 2A heterodimer in the nucleus accumbens could be the basis for their psychotic actions [ 171 ]. This fact can also supply a better description of the molecular mechanism of the therapeutic effects of the second-generation antipsychotics, such as risperidone and clozapine, which block the 5-HT 2A receptor with higher potency than the D 2 receptor. It can be postulated that, in some cases of schizophrenia, this pathological facilitating interaction between 5-HT 2A and D 2 receptors has developed in the 5-HT 2A –D 2 heterodimer leading to increased D 2 protomer recognition and signaling [ 171 ]. Interestingly, 5-HT 2A or D 2 receptor antagonists acting selectively on this heterodimer or compounds disrupting the heterodimer interface might be a novel strategy to treat schizophrenia. Regarding other dimers with possible involvement in the pathomechanism of schizophrenia, mGluR2–5-HT 2A heteromer should be mentioned [ 172 ] This complex displays unique signaling when interacting with hallucinogenic drugs and activation of mGluR2 cancels hallucinogenic signaling and related behavioral responses. In postmortem studies of human brains from untreated schizophrenic subjects, the 5-HT 2A receptor is up-regulated and the mGluR2 is down-regulated which can predispose to psychosis.

5. Other Non-Classical Approaches for the Treatment of Schizophrenia

The limitations of current antipsychotics are supplemented by reports about involvement of neurtotransmitter systems other than the dopaminergic system, especially glutamate neurotransmission that contributes to the pathomechanism of schizophrenia. Thus, new drug targets resulting in drugs with novel mechanisms of action have been proposed. In particular, glutamate and nicotinic targets seems promising [ 173 , 174 ]. Selective ligands for metabotropic glutamate receptor, phosphodiesterase, glycine transporter subtype 1 and the alpha7 nicotinic acetylcholine receptor are considered worth further investigation [ 173 , 174 ].

Regarding metabotropic glutamate receptors, potentiation of mGluR2/3 and mGluR5 receptors can be beneficial in schizophrenia [ 175 ]. Although classical orthosteric agonists are still an option, subtype-selective allosteric ligands, including positive allosteric modulators of mGluR2 and mGluR5 can offer numerous advantages brought by allosteric mode of action.

Phosphodiesterase (PDE) inhibitors improve neurotransmission by affecting intracellular second messenger signaling [ 176 ]. In particular, inhibitors of PDE2, PDE4, PDE5 and PDE10 seem promising for treating cognitive symptoms of schizophrenia.

Glycine transporter 1 inhibitors applied in combination with antipsychotics are effective for relieving negative symptoms of the disease. α7 nicotinic receptor agonists and positive allosteric modulators and minocycline may treat negative and cognitive symptoms. Complementary oxytocin may help to ameliorate psychotic symptoms and social cognitive deficits. Complementary erythropoietin might benefit cognitive function [ 174 ].

6. Conclusions and Future Prospects

Although current concept and treatment of schizophrenia are still based on the dopaminergic hypothesis of the disease, novel approaches involving new signaling mechanisms on classical drug targets or completely new targets emerge. Schizophrenia is a complex multi-factor disease and according to the current knowledge it does not seem very probable that all symptoms of the disease can be treated with a single-target drug. Indeed, clozapine, which is used to treat resistant schizophrenia has a nanomolar affinity to a dozen of aminergic GPCRs. Searching for multi-target drugs beyond aminergic GPCRs may be a promising strategy to design better antipsychotics. Moreover, novel signaling mechanisms of GPCRs can lead to safer drugs with fewer side effects, e.g., allosteric modulators or biased ligands or even with tissue specificity (dimer-selective ligands). Current efforts in drug design against schizophrenia focus on searching for compounds to treat negative symptoms and to improve cognitive deficits as well as searching for compounds that are better tolerated by patients who often need life-lasting treatment.

In summary, after over a century of schizophrenia treatment, significant progress has been achieved, starting from lobotomy operations, through discovery of chlorpromazine to current second- and third-generation antipsychotics. Novel approaches, following new findings in the disease mechanisms, will finally result in new generations of drugs.

Author Contributions

P.S. wrote Section 3 ; M.K. wrote Section 2 ; and A.A.K. wrote Section 1 , Section 4 , Section 5 and Section 6 .

The work was performed under OPUS grant from National Science Center (NCN, Poland), grant number 2017/27/B/NZ7/01767.

Conflicts of Interest

The authors declare no conflict of interest.

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Global analysis of cancer research papers reveals consistent sex imbalance

by King's College London

A new study from the Lancet Commission on Women, Power and Cancer with the Institute of Cancer Policy at King's has revealed a consistent sex imbalance of global cancer researchers across a 10 year period.

Published in BMJ Oncology , the study found the proportion of women as first authors increased by 26% and as last authors by 12%. However, this average obscures tremendous variability between regions and countries, with some of the richest countries on the planet languishing at the bottom of the index.

"Understanding country level participation of women in cancer research is crucial for benchmarking and developing evidence-driven policy to improve equity," said Director, Institute of Cancer Policy, King's College.

The researchers looked at the total output of cancer research papers from 56 countries between 2009 and 2019. They specifically analyzed the percentage of first authors, who are the publication lead considered to have made the biggest contribution, and last authors, who are usually the supervisor of the project and in a leadership position like laboratory group leader.

Broadly, countries in the Far East, Middle East (except North Africa), Western Europe (UK, Germany), as well as North America, performed poorly. Countries such as South Korea, Saudi Arabia, Austria, Greece and Japan languished at the bottom of the table—the last of which recorded 19.1% of first authors and 5% of last authors being female in 2019. Some countries showed a stagnation or decline in the number of female last authors.

In contrast, generally, the top performing countries in terms of first and last authors were in Eastern and Southern Europe and Latin America, with countries such as Argentina, Portugal, Serbia and Romania registering at the top of the table.

While it is not possible to tease out the reasons from this study alone, the authors suggest the results are consistent with the general inadequacy of effective and sustained efforts to support women's academic advancement. They add that women still bear the majority of social and familial care giving responsibilities and are more likely to leave academia from experiencing a hostile workplace culture, as potential barriers against gender equity .

The more positive results from Eastern Europe, on the other hand, could be partly due to a complex post-Soviet phenomenon of the "feminization" of science and medicine. The authors also note that the availability of affordable childcare could be a factor within EU countries.

Overall, female authors were also more likely to publish in lower impact journals, and less likely to be cited than male authors. This is consistent with previous research in gender equity within science which has been described as the "Matilda effect"—the phenomenon that women are more likely to be under-recognized in scientific publishing.

These results show that more work is required to support gender equity and women in academia, and follows the Women, power and cancer: A Lancet report that called for greater female representation within publishing and leadership in oncology research.

"Research funding organizations need to review their gender equity policies for cancer research and countries need to create better systems for supporting women scientists and clinicians more broadly," said Professor Miriam Mutebi, President, African Organization for Research and Training In Cancer.

This will require more research to understand the factors driving representation in successful and unsuccessful countries, which the authors hope can inform policy to improve female representation within oncology research.

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Open access
Published: 18 May 2024

The contribution of prosody to machine classification of schizophrenia

Tomer Ben Moshe 1 ,
Ido Ziv 2 ,
Nachum Dershowitz 1 &
Kfir Bar 3

Schizophrenia volume 10 , Article number: 53 ( 2024 ) Cite this article

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Schizophrenia

We show how acoustic prosodic features, such as pitch and gaps, can be used computationally for detecting symptoms of schizophrenia from a single spoken response. We compare the individual contributions of acoustic and previously-employed text modalities to the algorithmic determination whether the speaker has schizophrenia. Our classification results clearly show that we can extract relevant acoustic features better than those textual ones. We find that, when combined with those acoustic features, textual features improve classification only slightly.

Speech- and text-based classification of neuropsychiatric conditions in a multidiagnostic setting

Automatic language analysis identifies and predicts schizophrenia in first-episode of psychosis

Relative importance of speech and voice features in the classification of schizophrenia and depression

Introduction.

Schizophrenia is an acute mental disorder characterized by delusions, hallucina- tions, and thought disorders. Thought disorders are disturbances in the normal way of thinking, typically presented as various language impairments, such as disorganized speech, which are related to abnormal semantic associations between words 1 . These include the following: (1) poverty of speech; (2) pressure of speech, fast, loud and hard-to-follow responses; (3) “word salad”, random-word selection at times; (4) derailment, shifting from one topic to another during a conversation; and (5) tangentiality, furnishing an irrelevant response, never reaching the answer to the posed question 2 . Andreasen 3 provides some statistics for symptoms of thought disorder, with the most common being derailment, loss of goal, poverty of content, and tangentiality.

Diagnosing thought disorders is performed by clinicians and mental-health professionals, typically by means of a conversation. This is an arduous and subjective process. Mental-health professionals are on constant lookout for objective computational assessment tools that can help identify whether a person is showing signs of thought disorders.

There have been several prior attempts at developing computational tools for analyzing language with the goal of detecting symptoms of mental-health disorders; we describe some of those works in the following section. Generally speaking, speech and text are the two modalities of human language that can be processed and analyzed algorithmically for the diagnosis of mental-health disorders. For this purpose, processing speech is typically done for the purpose of modeling the prosody by extracting features related to intonation, stress and rhythm. One of the most prominent prosodic symptoms is flattened intonation, or aprosody, which is interpreted as inability of a person to properly convey emotions through speech. This is a negative symptom of schizophrenia. Another negative symptom that is associated with speech is alogia, or poverty of speech, presented as very minimal speech. Metaphorically, it has been claimed 4 , 5 that patients with schizophrenia sometimes sound like a person talking on the phone, referring to the low-quality aspect of the voice, sometimes occasionally to as a “creaky” voice. Cohen et al. 6 associate acoustic-based analysis of speech, generally speaking, with clinically rated negative symptoms, while associations with positive symptoms have been found to be inconsistent.

Prosody, which encompasses aspects of language beyond the scope of grammar and vocabulary choice, can reflect subtle elements such as emotions and pragmatic nuances. Conversely, the transcription is essential for capturing the linguistic and semantic characteristics inherent in conversations. It’s important to note, however, that non-emotional aspects of prosody also exist and play a significant role in communication.

We study the salience of acoustic and textual features for the classification task of automatically detecting whether a given utterance was generated by someone who has been diagnosed with schizophrenia or by a control subject. To do that, we measure the contribution of each set of features once when used individually for classification, and again when both modalities are combined together.

Our dataset comprises transcribed interviews, collected from native Hebrew-speaking inpatients, officially diagnosed with schizophrenia at a mental health center in Israel, and from a demographically balanced control group. The prosodic features that we consider are based on pitch, which we extract using an audio processor. The textual features are extracted from the transcriptions of the audio files and are designed to capture symptoms such as derailment and incoherence, following a previous work 7 that has shown the efficacy of such features when used in a similar classification task.

Prosodic features have been computationally examined previously and were shown to be effective for the task of detecting schizophrenia—for example 8 , 9 for English speech. For Chinese, Huang et al. 10 combined acoustic features with textual features for assessing the severity of thought disorders in examined schizophrenia patients. However, none of these works compare the individual contributions to classification of each of the modalities when used in combination.

Our contribution is twofold: (1) We show how acoustic prosodic features can be used for detecting symptoms of schizophrenia from only a single spoken response (given in Hebrew); and (2) we measure the individual contribution of both speech and text modalities to the task of detecting whether the person who generated a given utterance has schizophrenia. Our classification results clearly show that the acoustic prosodic features capture more information than do the textual ones. When combined with those acoustic features, textual features improve classification very slightly.

Related work

The extensive literature about language characteristics and schizophrenia is examined in 11 . The authors distinguish between two types of language impairment among patients with schizophrenia: thought disorder—defined as disturbances in the normal way of thinking, and schizophasia—comprising various dysphasia-like impairments such as clanging, neologism, and unintelligible speech. They also assert that patients with thought disorders produce and perceive sounds in an abnormal way, manifesting as flat intonation or unusual voice quality.

Hoekert et al. 12 conducted a meta-analysis of seventeen studies between 1980 and 2007. They found that prosodic expression of emotions is significantly impaired with schizophrenia. Martínez-Sánchez et al. 13 compared the speech of 45 medicated schizophrenia patients and 35 healthy controls, all native Spanish speakers from Spain. The results revealed that patients paused more, talked more slowly, and showed less variability in speech and fewer variations in syllable timing. Alpert et al. 14 examined whether “flat affect”, defined as emotionless speech, which is one of the symptoms of schizophrenia, indicates an emotional deficiency or whether this is only a communication issue. They did not find evidence for impairment in any other aspect of emotion expression besides prosody.

There is a large body of work that studies the efficacy of computational approaches for diagnosis of mental-health disorders. We continue by listing some related work that use computational tools to process acoustic speech signals for diagnosis of mental-health disorders, followed by works that use natural-language processing tools for analyzing transcriptions for the same purpose.

In a systematic review 15 that analyzes 127 studies, the authors conclude that speech processing technologies could aid mental-health assessment; however, they mention several caveats that need to be addressed, especially the need for comprehensive transdiagnostic and longitudinal studies. Given the diverse types of datasets, feature extraction procedures, computational methodologies, and evaluation criteria, they provide guidelines for both data acquisition and building machine-learning models for diagnosis of mental-health disorders.

Kliper et al. 8 trained a support vector machine (SVM) classifier that gained about 76% accuracy in a binary classification task of identifying people with schizophrenia versus controls, using acoustic features. The study population comprized 62 English-speaking participants, divided into three groups: patients with schizophrenia, patients with clinical depression, and healthy controls. In a three-way classification task over the three groups, their classifier achieved about 69% accuracy. Every participant was interviewed and recorded by a mental-health professional. Each recording was divided into segments of two minutes each, which were subsequently analyzed independently. Each recording was represented by nine acoustic features based on pitch and power, which were automatically extracted using tools similar to those that we use in this work.

Dickey et al. 16 study prosodic abnormalities in patients with schizoid personality disorder (SPD). Their experimental results showed that SPD patients speak more slowly, with more frequent pauses, and exhibited less pitch variability than control participants.

A new algorithm to detect schizophrenia was proposed by 17 based on a classifier that uses three new acoustic prosodic features. On a dataset comprised of 28 schizophrenia patients and 28 healthy controls, they measured classification accuracy between 89.3% and 94.6%.

Agurto et al. 18 predict psychosis in youth using various acoustic prosodic features, such as pitch-related and Mel-frequency cepstral coefficients (MFCC). They analyzed the recorded speech of 34 young patients who were diagnosed to be at high risk of developing clinical psychosis. Among other things that they showed, they trained a classifier that can predict the development of psychosis with 90% accuracy, outperforming classification using clinical variables only.

Lucarini et al. 19 offer a review of research papers focusing on the less-explored topic of non-emotional prosody. They introduce a linguistic model designed to classify prosodic functions along a continuum ranging from “linguistic,” pertaining to the structural aspects of language, to “paralinguistic,” which relates to the expression of emotions.

Lucarini et al. 20 conducted an analysis of conversations between patients with schizophrenia and interviewers, aiming to detect associations between symptoms of schizophrenia and conversation dynamics. The approach centered on a relatively straightforward representation of a conversation, primarily encoding pauses and participant involvement. Their findings indicate a significant association between the dynamics of these conversations and negative symptoms of schizophrenia.

There has been an increasing number of works that computationally process speech transcriptions for detecting symptoms of schizophrenia. Specifically, measuring derailment and tangentiality has been addressed several times. For example, Elvevåg et al. 21 analyzed transcribed interviews of inpatients with schizophrenia by calculating the semantic similarity between the response given the participants and the question that was asked by the interviewer. For semantic similarity they used cosine similarity over the latent semantic analysis (LSA) vectors 22 calculated for each word, and summed across a sequence of words. Similarly, Bedi et al. 23 use cosine similarity between pairs of consecutive sentences, each represented by the element-wise average vector of the individual words’ LSA vectors, to measure coherence. Using this score they automatically predicted transition to psychosis with perfect accuracy. Iter et al. 24 showed that removing some functional words from the transcriptions improves the efficiency of using cosine similarity over LSA vectors for measuring derailment and incoherence.

This direction was developed further by Bar et al. 7 , who used fastText vectors 25 to measure derailment in a study group that included 24 schizophrenia patients and 27 healthy controls, all native Hebrew speakers. Furthermore, they developed a new metric for measuring some aspects of incoherence, which compares the adjectives and adverbs that are used by patients to describe some nouns and verbs, respectively, with the ones used by the control group. As a final step, they used derailment and incoherence scores as features for training a classifier to separate the two study subgroups. In another work 26 on the same study group, the authors used part-of-speech tags, lemma-to-token ratio, and some other morphological features, to perform a two-way classification for patients and controls. They report almost 90% accuracy.

We study a similar group of Hebrew-speaking male schizophrenia patients and healthy controls. Therefore, we use some of the same textual features suggested in that prior work to measure their respective contributions when combined with acoustic features.

Corona-Hernández et al. 27 analyzed speech transcriptions of Dutch-speaking schizophrenia patients and controls, focusing on how connectives serve as informative and explainable variables. That study aimed to determine the reliability of using connectives to assess disorganized speech in patients with schizophrenia.

Finally, Corcoran et al. 28 present a survey of various studies that employ similar techniques for measuring symptoms of psychosis and schizophrenia, by automatically analyzing speech transcriptions.

Methodology

Participants and data collection.

We interviewed 48 men, aged 18–60, divided into control and patient groups, all speaking Hebrew as their first language. The patient group includes 23 inpatients from the Be’er Ya’akov–Ness Ziona Mental Health Center in Israel who were admitted following a diagnosis of schizophrenia. Diagnoses were made by a hospital psychiatrist according to the DSM-5 criteria (American Psychiatric Association, 2013) and a full psychiatric interview. Each participant was rewarded with approximately $8. The control group includes 25 men, mainly recruited via an advertisement that we placed on social media. The demographic characteristics of the two groups are given in Table 1 . Exclusion criteria for all participants were as follows: (1) participants whose mother tongue is not Hebrew; (2) having a history of dependence on drugs or alcohol over the past year; (3) having a past or present neurological illness; and (4) using fewer than 500 words in total in their transcribed interview. Additionally, the control group had to score below the threshold for subclinical diagnosis of depression and post-traumatic stress disorder (PTSD). Most of the control participants scored below the threshold for anxiety. Most of the patients scored above the threshold for borderline or mild psychosis symptoms on a standard measure. (Our patient group is composed of inpatients who are being treated with medications; therefore, higher scores were not expected.) See Section 3.2 for more details about the assessment measures used in this study.

The patients were interviewed in a quiet room at the department where they are hospitalized by one of our professional team members, and the control participants were interviewed in a similar room outside the hospital. Each interview lasted approximately 60 min. The interviews were recorded and later manually transcribed by a native Hebrew speaking student from our lab. All participants were assured of anonymity, and told that they are free to end the interview at any time.

After signing a written consent, each participant was asked to describe 14 black and white images picked from the Thematic Appreciation Test (TAT) collection. We used the TAT images identified with the following serial numbers: 1, 2, 3BM, 4, 5, 6BM, 7GF, 8BM, 9BM, 12 M, 13MF, 13B, 14, and 3GF. These include a mixture of men and women, children, and adults. The images were presented one by one. Each picture stands by itself, was presented alone, and bears no relation to the other pictures. Participants were asked to tell a brief story about each image based on four open questions:

What led up to the event shown in the picture?

What is happening in the picture at this moment?

What are the characters thinking and feeling?

What is the outcome of the story?

The interviewer remained silent during the respondent’s narration and offered no prompts or additional questions.

After describing the images, the participant was also asked to answer four open-ended questions, one by one:

Please tell me as much as you can about your bar mitzvah . (The Jewish confirmation ceremony for boys upon reaching the age of 13)

What do you like to do, mostly?

What are the things that annoy you the most?

What would you like to do in the future?

As before, the interviewer remained silent during the respondent’s narration and offered no prompts or questions.

Once all 18 components (14 image descriptions and 4 open questions) were answered, each participant was requested to fill in a demographic questionnaire as well as some additional questionnaires for assessing mental-health symptoms, which we describe in the following subsection.

NB. This research was approved by the Helsinki Ethical Review Board (IRB) of the Be’er Ya’akov–Ness Ziona Mental Health Center .

Symptom assessment measures

Control group.

The control participants were assessed for symptoms of depression, PTSD, and anxiety.

Symptoms of depression were assessed using Beck’s Depression Inventory-II (BDI-II) 29 . The BDI-II is a 21-item inventory rated on a 4-point Likert-type scale (0 = “not at all” to 3 = “extremely”), with summary scores ranging between 0 and 63. Beck et al. 29 suggest a preliminary cutoff value of 14 as an indicator for mild depression, as well as a threshold of 19 as an indicator for moderate depression. BDI-II has been found to demonstrate high reliability 30 . We used a Hebrew version 31 .

Symptoms of PTSD were assessed using the PTSD checklist of the DSM-5 (PCL-5) 32 . The questionnaire contains twenty items that can be divided into four subscales, corresponding to the clusters B–E in DSM-5: intrusion (five items), avoidance (two items), negative alterations in cognition and mood (seven items), and alterations in arousal and reactivity (six items). The items are rated on a 5-point Likert-type scale (0 = “not at all” to 4 = “extremely”). The total score ranges between 0 and 80, provided along with a preliminary cutoff score of 38 as an indicator for PTSD. PCL-5 has been found to demonstrate high reliability 33 . We used a Hebrew translation of PCL-5 34 .

Symptoms of anxiety were assessed through the State Trait Anxiety Inventory (STAI) 35 . The STAI questionnaire consists of two sets of twenty self-reporting measures. The STAI measure of state anxiety (S-anxiety) assesses how respondents feel “right now, at this moment” (e.g., “I feel at ease”; “I feel upset”), and the STAI measure of trait anxiety (T-anxiety) targets how respondents “generally feel” (e.g., “I am a steady person”; “I lack self-confidence”). For each item, respondents are asked to rate themselves on a 4-point Likert scale, ranging from 1 = “not at all” to 4 = “very much so” for S-anxiety, and from 1 = “almost never” to 4 = “almost always” for T-anxiety. Total scores range from 20 to 80, with a preliminary cutoff score of 40 recommended as indicating clinically significant symptoms for the T-anxiety scale 36 . STAI has been found to have high reliability 37 . We used a Hebrew translation 38 .

Psychosis symptoms were assessed by the 6-item Positive And Negative Syndrome Scale (PANSS-6) 39 . The original 30-item PANSS (PANSS-30) is the most widely used rating scale in schizophrenia, but it is relatively long for use in clinical settings. The items in PANSS-6 are rated on a 7-point scale (0 = “not at all” to 6 = “extremely”). The total score ranges from 0 to 36, with a score of 14 representing the threshold for mild schizophrenia, and a score between 10 and 14 defined as borderline disease or as remission. PANSS-30 has been found to demonstrate high reliability 40 , while Østergaard et al. 39 reported a high correlation between PANSS-6 and PANSS-30 (Spearman correlation coefficient = 0.86). We used the Hebrew version of PANSS-6 produced by Katz et al. 41 . The range of positive and negative symptoms are presented in the last three rows of Table 1 .

Data analysis

We analyse the data using two modalities, audio and text. All the interviews were recorded with a voice recorder, which was placed on the table next to the participant. The responses of the participants for each of the 18 interview components were recorded separately, and stored as individual files in Waveform Audio File Format (WAV). Each response was manually transcribed. We extracted prosodic acoustic features from the audio signal, as well as textual features from the corresponding transcriptions.

Prosodic acoustic features

We processed each WAV file with PRAAT 42 , a computer software package for speech analysis, in order to extract pitch and intensity per 10 ms frame. We use the PRAAT “Sound: To Pitch” method, assigned with its standard values, to detect frames with fundamental-frequency (F0) above 75 Hz. Typically, males’ pitch ranges between 75 Hz and 180 Hz and females’ from 80 Hz to 250 Hz. Furthermore, we noticed that some external noises occur in high frequencies. Therefore, we distinguish between speech and non-speech frames by automatically annotating as speech those frames with a detected F0 value above 75 Hz and below 250 Hz. Overall, we processed 18,187,506 10 ms frames, corresponding to approximately 50 h of recordings, out of which 8,377,628 frames had an F0 above 75 Hz. Only 322,189 (approximately 4% of 8 M frames) were above the 250 Hz threshold, resulting in 8,055,439 frames that we treated as carrying human speech. We acknowledge that errors may have occurred during the pitch-extraction process; we did not employ any correction utilities for the extraction. Additionally, we are aware that the voiceless sounds characteristic of Hebrew could potentially lead to some frames being misclassified as non-speech.

Each WAV file, corresponding to a response to a single image/question, is now represented by a sequence of speech frames, each represented by a pair of pitch and intensity values. We extract nine feature types from each response; to avoid overfitting, we filter out responses representing less than 10 seconds worth of speech. Therefore, we work with a dataset containing 449 responses given by controls and 409 responses given by patients. Following previous work on computational prosodic analysis 8 , we extracted the following set of features:

Mean Utterance Duration (MUD)

Every segment of at least 500 ms of continuous speech is defined as an utterance . MUD is the mean duration (in ms) of all the utterances in a given response. The threshold of 500 ms corresponds to 50 consecutive frames with a pitch value indicative of speech. Considering our criteria for identifying speech within a frame, there is a potential for omission of speech signals that could have been analyzed. However, given our focus—in this study—on comparing textual and acoustic features, we chose to concentrate on speech segments with a high likelihood of containing substantive content for meaningful extraction of both feature types.

Mean Gap Duration (MGD)

A gap is defined as a maximal time interval containing no speech. MGD is the mean length (in ms) of all gaps in a given response.

Mean Spoken Ratio (MSR)

The sum of the durations of all utterances in a response divided by the total response duration.

Mean Spoken Ratio Samples (MSRS)

The number of frames that are classified as speech divided by the total number of frames in the response.

Mean Pitch (MP)

The mean pitch (in Hz) of all frames recognized as speech in a given response.

Pitch Range (PR)

The maximum pitch of all frames recognized as speech, minus their minimum value, and divided by MP for normalization.

Standard Deviation of Pitch in a Single Response (PS)

The standard deviation of pitch (in Hz) of all frames recognized as speech in a given response.

Frame Pitch Correlation (FPC)

The Pearson correlation between a sequence of pitches of speech frames and a sequence of pitches of their consecutive frames in a given response. FPC, the way it is applied on pitch, measures the level at which the speaker sustains constant pitch. FPC is equivalent to mean waveform correlation (MWC), suggested in ref. 8 .

The local deviation from stationarity of pitch. Formally, let R be the number of speech frames, and let p ( v ) be the pitch of the v th frame. We define J as follows:

K is a locality parameter; it was set to 5 in all our experiments. Jitter quantifies the variability of a given measurement within a specific local context, determined by the locality parameter K . In other words, it assesses the stability of the time period within an environment spanning five consecutive frames.

We did not extract features that are based on intensity since we noticed some differences in the background noise between the recordings of the control participants and the patients, probably due to differences in room settings and recording equipment.

We verified that all the features are distributed normally, as expected, and performed t tests to measure the difference in feature expression between patients and controls. The results are summarized in Table 2 . As can be seen, all the features associated with speech rate (MUD, MGD, MSR, MSRS) are distributed significantly differently among patients and controls. MGD exhibits relatively high levels of variability as indicated by the relatively large standard deviation. Consistent with other research 8 , our findings indicate that controls generally exhibit more fluent speech, characterized by significantly shorter pauses. These results should be qualified by a reminder that we consider only utterances that comprise at least 50 consecutive pitch frames marked as speech. Therefore, an MSR value of 0.124 (12%) for the patients does not necessarily mean that the patients speak for only 12% of the response time on average. It primarily means that only 12% of the signal is treated as substantive speech. Consequently, there is no intention to use the findings in Table 2 to draw direct conclusions about the speech patterns of participants. We primarily use these values as features for classification, as explained below. Conversely, analysis reveals that the mean pitch (MP) and pitch standard deviation (PS) of a given response are relatively comparable across the two groups. Nevertheless, more nuanced metrics derived from pitch values, such as jitter (J), frame pitch correlation (FPC), and pitch range (PR), demonstrate a more pronounced distinction between the groups. Upon examination of the jitter calculation methodology, it becomes apparent that the differences in pitch across consecutive frames may significantly contribute to the differentiation between the two groups. The explanation is the fact that jitter is calculated locally over five consecutive frames as defined by the locality parameter. The standard deviation of PS (5.517 and 7.370 for control and patients, respectively) indicates that there are some responses with high pitch variability, which in turn facilitates greater jitter variability. We ascribe the same explanation to the pronounced difference in FPC between the two groups, resulting in a more significant difference between them. The FPC values (0.581 and 0.483 for controls and patients, respectively) suggest that control participants exhibit a more consistent prosody while responding to questions compared to patients.

We also experimented with a different method of calculating pitch range, dividing by the minimum pitch value instead of the mean value. The average and standard deviation for the control participants and patients using this alternate calculation were 1.814 (0.226) and 1.367 (0.383), respectively. This also resulted in a significant difference [ t = −4.96 ( p < 0.001***)] between the two groups. However, the distribution of this new pitch range variation did not differ markedly from the original.

Textual features

We extract the same textual features that have been used by Bar et al. 7 on a similar dataset. Essentially, they designed two types of features for capturing specific symptoms of thought disorder.

The first type is designed to capture derailment, which is a symptom of thought disorder when the speaker digresses from the main topic. Technically speaking, we represent words using static embeddings provided by fastText 43 for Hebrew. For each response, we retrieve the fastText vector v i for every word R i , i = 0 ..n , in the response. Then, for each word, we calculate a score defined as the average pairwise cosine similarity between this word and the k following words, with k a variable parameter. The score of a response is the average of all the individual cosine-similarity scores. To filter out functional words that do not contribute to the topical mutation assessment, we follow 7 by pre-processing each response with a Hebrew part-of-speech tagger 44 and keep only content words, which we take to be nouns, verbs, adjectives, and adverbs.

We calculate derailments for k = 1..6, thereby extracting six derailment features per response.

Incoherence

One of the most informative features reported in 7 was designed to capture some aspects of discourse related to incoherence. Specifically, this feature examines the way patients use adjectives to describe specific nouns. The goal is to measure the difference between adjectives used by patients and the ones used by controls when describing the same nouns. Technically speaking, we process each response with YAP 45 , a dependency parser for Modern Hebrew, to find all noun-adjective pairs (indicated by the amod relation). To measure the difference between adjectives that are used by patients and controls, we compare them to the adjectives that are commonly used to describe the same nouns. To do that, following the above-mentioned work, we use an external corpus of health-related documents and forums, all written in Hebrew, containing nearly 680K words. (We use the same sources as in 7 ). We process each document in exactly the same way to find all noun- adjective pairs. Given a list of noun-adjective pairs from one response, we calculate the similarity score between every adjective that describes a specific noun and the set of adjectives describing exactly the same noun across the entire external corpus. Hebrew enjoys a rich morphology; therefore, we work on the lemma (base-form) level. The lemmata are provided by YAP . We take the fastText vectors of the adjectives that were extracted from the external corpus and average them, element wise, into a single vector by assigning weights to each individual vector.

The weights are the inverse-document-frequency (idf) score of each adjective, to account more heavily for adjectives that describe the noun more uniquely. Then, we take the cosine similarity between each adjective from the response and the aggregated vector of the adjectives from the external corpus. For each response, we take the average of the individual adjective cosine-similarity scores as the overall response incoherence score.

As before, we verified that all our features are distributed normally and performed t -tests to measure the difference in feature expression between patients and controls. The results are summarized in Table 3 . In contrast with the outcomes in 7 , we see no evidence for different distributions of each individual textual feature between the two groups. The datasets, patients and controls, differ for the two experiments. In 7 , the controls were told to talk for at least two minutes, which potentially impacted the outcome.

Classification

We train a two-way machine-learning classifier to distinguish between responses that were generated by patients and controls. Each response is used as a classification instance, assigned either a “patient” or “control” label depending on the group to which the subject who generated the response belongs. Overall we have 449 responses generated by controls and 409 responses by patients. We ran three sets of experiments: (1) using only the acoustic features (Acoustic); (2) using only the textual features (Textual); and, (3) using both feature sets (Combined). Consequently, each response is represented by a nine-dimensional vector in the first set of experiments, a seven-dimensional vector in the second set, and a 16-dimensional vector in the third set of experiments.

For classification, we used three traditional machine-learning algorithms: XG-Boost 46 , Random Forest 47 , and Linear SVM 48 .

We measured the classification results using accuracy and the F1 score of the patient label. For each classifier, we ran five evaluations, each time taking a five-fold cross-validation approach. Every evaluation had a different random seed, which was kept similar across all classifiers. The five results were calculated as the average over the five evaluation runs. The results, divided into the three feature sets, are presented in Table 4 .

Overall, the XGBoost algorithm achieves the best classification performance when utilizing solely the acoustic features. When using only the textual features, all the classifiers perform poorly. Furthermore, combining the textual features with the acoustic ones did not usually result in significant performance improvement, suggesting that the contribution of our textual features to the classification performance on the dataset is limited and redundant when the acoustic features are used for detecting symptoms of schizophrenia. The lesser success with textual features may be due in part to the inherent difficulty of accurately measuring semantic features like derailment and incoherence computationally.

Our best accuracy for the two-way classification task is around 90%, which is higher than the best accuracy of about 76% reported by Kliper et al. 8 using a similar set of acoustic features for the same two-way classification task with an English-speaking population.

Looking at the demographic characteristics of the participants in Table 1 , we notice that the patients and controls significantly differ in age and years of education. Therefore, we performed a complementary analysis to support the current findings in which seven sets of multiple regressions have been carried out as reported in Table 5 . These represent the seven prosodic features which demonstrated a significant (at least p < 0.05) different distribution among patients and controls. As shown in Table 3 , none of the textual features has been shown to be different among the two groups.

As can be seen from Table 5 , years of education consistently did not associate with any of the prosodic features. The age characteristic was associated significantly ( p = 0.047) only once with MGD. However, the group (patients/control) was the only predictor that was associated consistently, substantially, and significantly with all the prosodic features.

We acknowledge potential variability in patient interactions during the interviews, as recently demonstrated in a study by Cangemi et al. 49 , which analyzed both speech and non-speech segments of patients with schizophrenia. Additionally, while the average PANSS-total score in our study is 17.34, above the threshold of 14, the considerable standard deviation of 6.29 indicates the presence of borderline cases and possibly some patients in remission. Specifically, among our sample of 23 patients, two have PANSS scores below 10, and three have scores between 10 and 14, suggesting that five patients could be considered in remission. Our current study primarily examines the influence of two feature sets—acoustic and textual—on classification outcomes, as detailed in Table 4 . Although patient interactions may vary, we believe that analyzing these feature sets within the same group of patients is a valid approach. Furthermore, in an additional analysis, we observed a significant association, beyond mere chance, between these feature sets and the PANSS-total score. The analysis involved clustering the 23 patients into 2, 3, and 8 clusters, performed independently. We conducted the experiments twice, representing patients once with textual features and once with acoustic features. The k -means algorithm was employed for clustering, and the mutual information (MI) metric was used to assess the relationship between the cluster assignment for each patient and their PANSS-total score. Given that the centroids in the k -means algorithm are randomly initialized, we ran each analysis 50 times to ensure reliability. This approach allowed us to report the average MI and its standard deviation. The MI scores, detailed in Table 6 , indicate that knowing a patient’s cluster assignment enhances the predictability of their PANSS-total score. These results suggest that the selected features vary in alignment with PANSS scores, reinforcing our primary conclusion that both acoustic and textual features are correlated with symptoms of schizophrenia.

We performed an ablation study to measure the effect of each feature individually. The results are summarized in Fig. 1 . As can be seen, MSRS, MUD and MGD are the most effective features; both are related to the pace of speech. It is noteworthy that removing certain features, primarily textual ones, slightly improves the performance of the classifier. The most significant one is FPC, which measures the level at which the speaker sustains constant pitch. Our hypothesis is that this is mainly a result of overlap in our feature descriptions.

The red line at 84.8 indicates the F1 value for XGBoost with all features included. The F1 scores the average of five executions, each using a different seed. Der. = Derailment; Inco. = Incoherence.

To measure the correlation between all the individual features, we calculate Pearson p for all feature pairs and summarize them in a heat map, as shown in Fig. 2 . Unsurprisingly, we see a strong correlation between all the textual derail- ment features, which makes them somewhat redundant for classification. Among the acoustic features, we see a stronger correlation between the standard deviation of the pitch (SP) and the frame pitch correlation (FPC). Generally speaking, both represent the dynamics of the pitch in speech frames. Similarly, and unsurprisingly, the mean spoken ratio (MSR) is strongly correlated with mean spoken ratio samples (MSRS); both represent the ratio between the time in which actual speaking is taking place and the overall time of the response. Naturally, gap duration (MGD) has a negative correlation with all the features that measure speaking duration. However, we do not find any significant correlation between the acoustic features and the textual ones. And, as seen in Table 4 , the textual features did not contribute added information for classification not already covered by the acoustic prosodic features.

Pearson p between all individual features, shown as a heat map.

We have extracted features from two modalities of Hebrew speech produced by schizophrenia patients during interviews and compared it with those of controls. Specifically, we extracted acoustic, prosodic features from the audio signal, as well as textual features of transcriptions of the interview that measure derailment and incoherence. Our main goal was to measure the contribution of each modality to classification performance, when used in combination. Generally speaking, we find that a traditional classification algorithm can nicely separate between the two groups, schizophrenia patients and healthy controls, with best accuracy of about 90%, which is better than the results that have been previously reported. The results also show that the textual features do not add much to classification performance when they are combined with the acoustic features that measure aspects of prosody.

Data availability

We have included a dataset as supplementary material, which details the values of all features for each participant, categorized by question.

Aloia, M. S. et al. Cognitive substrates of thought disorder, II: specifying a candidate cognitive mechanism. Am. J. Psychiatry 155 , 1677–1684 (1998).

Article CAS PubMed Google Scholar

American Psychiatric Association DSM-5 Task Force. Diagnostic and Sta- tistical Manual of Mental Disorders: DSM-5 . Vol. 5. (American Psychiatric Publishing, Washington, DC, 2013).

Andreasen, N. C. Thought, language, and communication disorders: II. Diagnostic significance. Arch. Gen. Psychiatry 36 , 1325–1330 (1979).

Cherry, C. in Disorders of Language: Ciba Foundation Symposium (eds. A. V. S. de Reuck and M. O’Connor. London: J. & A. Churchill), p. 294 (Archives of Internal Medicine, American Medical Association, 1964).

Spoerri, T. H. Speaking voice of the schizophrenic patient. Arch. Gen. Psychiatry 14 , 581–585 (1966).

Cohen, A. S., Kim, Y. & Najolia, G. M. Psychiatric symptom versus neurocognitive correlates of diminished expressivity in schizophrenia and mood disorders. Schizophr. Res. 146 , 249–253 (2013).

Article PubMed PubMed Central Google Scholar

Bar, K. et al. “Semantic characteristics of schizophrenic speech”. in Proceedings of the Sixth Workshop on Computational Linguistics and Clinical Psychology . June, pp. 84–93. https://doi.org/10.18653/v1/W19-3010 (Association for Computational Linguistics, Minneapolis, MN, 2019).

Kliper, R., Portuguese, S., & Weinshall, D. “Prosodic analysis of speech and the underlying mental state”. in International Symposium on Pervasive Computing Paradigms for Mental Health . pp. 52–62 (Springer, 2015).

Kliper, R., Vaizman, Y., Weinshall, D., & Portuguese, S. “Evidence for depression and schizophrenia in speech prosody”. in Pro- ceedings of the Third ISCA Workshop on Experimental Linguistics . Athens, Greece, pp. 35–38. https://www.isca-speech.org/archive_v0/exling_2010/papers/el10_085.pdf (2010).

Huang, Y.-J. et al. Assessing schizophrenia patients through linguistic and acoustic features using deep learning techniques. IEEE Transact Neural Syst. Rehabil. Eng. 30 , 947–956 (2022).

Article Google Scholar

Covington, M. A. et al. Schizophrenia and the structure of language: the linguist’s view. Schizophr. Res. 77 , 85–98 (2005).

Article PubMed Google Scholar

Hoekert, M., Kahn, R. S., Pĳnenborg, M. & Aleman, A. Impaired recognition and expression of emotional prosody in schizophrenia: review and meta-analysis. Schizophr. Res. 96 , 135–145 (2007).

Martínez-Sánchez, F. et al. Can the acoustic analysis of expressive prosody discriminate schizophrenia? Span. J. Psychol. 18 , E86 (2015).

Alpert, M., Rosenberg, S. D., Pouget, E. R. & Shaw, R. J. Prosody and lexical accuracy in flat affect schizophrenia. Psychiatry Res. 97 , 107–118 (2000).

Low, D. M., Bentley, K. H. & Ghosh, S. S. Automated as- sessment of psychiatric disorders using speech: a systematic review. Laryngoscope Investig. Otolaryngol. 5 , 96–116 (2020).

Dickey, C. C. et al. Prosodic ab- normalities in schizotypal personality disorder. Schizophr. Res. 142 , 20–30 (2012).

He, F., He, L., Zhang, J., Li, Y. Y. & Xiong, X. Automatic detection of affective flattening in schizophrenia: acoustic correlates to sound waves and auditory perception. IEEE/ACM Transact. on Au- dio, Speech Lang. Process. 29 , 3321–3334 (2021).

Agurto, C. et al. “Analyzing acoustic and prosodic fluctuations in free speech to predict psychosis onset in high-risk youths”. in 42nd Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC) . pp. 5575–5579 (IEEE, 2020).

Lucarini, V. et al. Speech prosody as a bridge between psychopathology and linguistics: the case of the schizophrenia spectrum. Front. Psychiatry 11 , 531863 (2020).

Lucarini, V. et al. Conversational metrics, psychopathological dimensions and self-disturbances in patients with schizophrenia. Eur. Arch. Psychiatry Clin. Neurosci. 272 , 997–1005 (2022).

Elvevåg, B., Foltz, P. W., Weinberger, D. R. & Goldberg, T. E. Quantifying incoherence in speech: an automated methodology and novel application to schizophrenia. Schizophr. Res. 93 , 304–316 (2007).

Deerwester, S., Dumais, S. T., Furnas, G. W., Landauer, T. K. & Harshman, R. Indexing by latent semantic analysis. J. Am. Soc. Inform. Sci. 41 , 391–407 (1990).

Bedi, G. et al. “Automated analysis of free speech predicts psychosis onset in high-risk youths”. npj Schizophr. 1, 15030. https://doi.org/10.1038/npjschz.2015.30 (2015).

Iter, D., Yoon, J., & Jurafsky, D. “Automatic detection of incoherent speech for diagnosing schizophrenia”. in Proc. Fifth Workshop on Computational Linguistics and Clinical Psychology: From Keyboard to Clinic . pp. 136–146 (Association for Computational Linguistics, 2018).

Bojanowski, P., Grave, E., Joulin, A., & Mikolov, T. “Enriching word vectors with subword information”. Trans. Assoc. Comput. Linguist. 5 , 135–146 (2017).

Ziv, I. et al. Morphological characteristics of spoken language in schizophrenia patients – An exploratory study. Scand. J. Psychol. 63 , 91–99 (2022).

Corona-Hernández, H., de Boer, J. N., Brederoo, S. G., Voppel, A. E. & Sommer, I. E. C. Assessing coherence through linguistic connectives: analysis of speech in patients with schizophrenia-spectrum disorders. Schizophr. Res. 259 , 48–58 (2023).

Corcoran, C. M. et al. Language as a biomarker for psychosis: a natural language processing approach. Schizophr. Res. 226 , 158–166 (2020).

Beck, A. T., Steer, R. A., Ball, R. & Ranieri, W. F. Comparison of beck depression inventories -IA and -II in psychiatric outpatients. J. Personal. Assess. 67 , 588–597 (1996).

Article CAS Google Scholar

Gallagher, D., Nies, G. & Thompson, L. W. Reliability of the beck depression Inventory with older adults. J. Consult. Clin. Psychol. 50 , 152–153 (1982).

Hasenson-Atzmon, K. et al. Cultural impact on SAD: Social anxiety disorder among Ethiopian and Former Soviet Union immigrants to Israel, in comparison to native-born Israelis. Israel J. Psychiatry 53 , 48–54 (2016).

Google Scholar

Weathers, F. W. et al. The PTSD checklist for DSM-5 (PCL- 5) . Scale available from the National Center for PTSD at www.ptsd.va.gov . (2013).

Blevins, C. A., Weathers, F. W., Davis, M. T., Witte, T. K. & Domino, J. L. The posttraumatic stress disorder checklist for DSM-5 (PCL-5): development and initial psychometric evaluation. J. Trauma. Stress 28 , 489–498 (2015).

Bensimon, M. et al. Elaboration on posttraumatic stress disorder diagnostic criteria: a factor analytic study of PTSD exposure to war or terror. Israel J. Psychiatry 50 , 84–90 (2013).

Spielberger, C. D., Gorsuch, R. L. & Lushene, R. E. STAI Manual for the State-Trait Anxiety Inventory (“self-evaluation questionnaire”) (Palo Alto: Consulting Psychologists Press,1970).

Knight, R. G., Waal-Manning, H. J. & Spears, G. F. Some norms and reliability data for the State-Trait Anxiety Inventory and the Zung Self-Rating Depression scale. Br. J. Clin. Psychol. 22 , 245–249 (1983).

Barnes, L. L. B., Harp, D. & Jung, W. S. Reliability generalization of scores on the Spielberger state-trait anxiety inventory. Educ. Psychol. Measure. 62 , 603–618 (2002).

Saka, N. & Gati, I. Emotional and personality-related aspects of persistent career decision-making difficulties. Journal of Vocational Behavior 71 , 340–358 (2007).

Østergaard, S. D., Lemming, O. M., Mors, O., Correll, C. U. & Bech, P. PANSS-6: A brief rating scale for the measurement of severity in schizophrenia. Acta Psychiatr. Scand. 133 , 436–444 (2016).

Lin, C.-H. et al. Early improvement in PANSS-30, PANSS- 8, and PANSS-6 scores predicts ultimate response and remission during acute treatment of schizophrenia. Acta Psychiatr. Scand. 137 , 98–108 (2018).

Katz, G. et al. A comparative study of Arab and Jewish patients admitted for psychiatric hospitalization in Jerusalem: The demographic, psychopathologic aspects, and the drug abuse comorbidity. Compr. Psychiatry 53 , 850–853 (2012).

Boersma, P. Praat: doing phonetics by computer . Computer program. http://www.praat.org (2011).

Grave, E., Bojanowski P., Gupta P., Joulin A., & Mikolov T. “Learning word vectors for 157 languages”. in Proc. International Conference on Language Resources and Evaluation (LREC 2018) . pp. 3483–3487 (European Language Resources Association (ELRA), 2018).

Adler, M. “Hebrew morphological disambiguation: an unsupervised stochastic word-based approach”. PhD thesis. Beer-Sheva, Israel: Ben-Gurion University of the Negev (2007).

More, A. & Tsarfaty, R. “Data-driven morphological analysis and disambiguation for morphologically rich languages and universal dependencies”. in Proc. 26th International Conference on Com- putational Linguistics (COLING) . Osaka, Japan, pp. 337–348. https://aclanthology.org/C16-1033.pdf (2016).

Chen, T. & Guestrin, C. “XGBoost: A scalable tree boosting system”. in Proc. 22nd ACM SIGKDD International Conference on Knowledge Discovery and Data Mining . pp. 785–794 (Association for Computing Machinery, 2016).

Liaw, A. et al. Classification and regression by ran- domForest. R News 2 , 18–22 (2002).

Cortes, C. & Vapnik, V. Support-vector networks. Machine Learn. 20 , 273–297 (1995).

Cangemi, F. et al. “Content-free speech activity records: interviews with people with schizophrenia”. in Language Resources and Evaluation , pp. 1–25 (Springer, 2023).

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Acknowledgements

We thank the Be’er Ya’acov Mental Health Center for their valuable collaboration that greatly contributed to this research. This research was supported by the Ministry of Science and Technology, Israel.

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Conceptualization, I.Z., N.D. and K.B.; methodology, All; implementation, T.B.M. and K.B.; validation, I.Z.; formal analysis, K.B., N.D. and I.Z.; investigation, K.B., N.D. and I.Z.; writing—original draft prepara- tion, K.B.; writing—review and editing, I.Z., N.D. and T.B.M.; supervision, I.Z., K.B. and N.D.; All authors have read and agreed to the published version of the manuscript.

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Ben Moshe, T., Ziv, I., Dershowitz, N. et al. The contribution of prosody to machine classification of schizophrenia. Schizophr 10 , 53 (2024). https://doi.org/10.1038/s41537-024-00463-3

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MIT physicists and colleagues have created a five-lane superhighway for electrons that could allow ultra-efficient electronics and more.

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In the current work, the team reports creating the superhighway without any magnetic field.

Tonghang Han, an MIT graduate student in physics, is a co-first author of the paper. “We are not the first to discover this general phenomenon, but we did so in a very different system. And compared to previous systems, ours is simpler and also supports more electron channels.” Explains Ju, “other materials can only support one lane of traffic on the edge of the material. We suddenly bumped it up to five.”

Additional co-first authors of the paper who contributed equally to the work are Zhengguang Lu and Yuxuan Yao. Lu is a postdoc in the Materials Research Laboratory. Yao conducted the work as a visiting undergraduate student from Tsinghua University. Other authors are MIT professor of physics Liang Fu; Jixiang Yang and Junseok Seo, both MIT graduate students in physics; Chiho Yoon and Fan Zhang of the University of Texas at Dallas; and Kenji Watanabe and Takashi Taniguchi of the National Institute for Materials Science in Japan.

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The phenomenon that the Ju group discovered in rhombohedral graphene that allows electrons to travel with no resistance at zero magnetic field is known as the quantum anomalous Hall effect. Most people are more familiar with superconductivity, a completely different phenomenon that does the same thing but happens in very different materials.

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Similarly, the rhombohedral graphene superhighway currently operates at about 2 kelvins, or -456 degrees Fahrenheit. “It will take a lot of effort to elevate the temperature, but as physicists, our job is to provide the insight; a different way for realizing this [phenomenon],” Ju says.

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The discoveries involving rhombohedral graphene came as a result of painstaking research that wasn’t guaranteed to work. “We tried many recipes over many months,” says Han, “so it was very exciting when we cooled the system to a very low temperature and [a five-lane superhighway operating at zero magnetic field] just popped out.”

Says Ju, “it’s very exciting to be the first to discover a phenomenon in a new system, especially in a material that we uncovered.”

This work was supported by a Sloan Fellowship; the U.S. National Science Foundation; the U.S. Office of the Under Secretary of Defense for Research and Engineering; the Japan Society for the Promotion of Science KAKENHI; and the World Premier International Research Initiative of Japan.

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1. Introduction

2. Schizophrenia as a Complex Disease

2.2. Glutamatergic Hypothesis

2.3. Serotoninergic Hypothesis of Schizophrenia

2.4. Other Aminergic GPCRs in Schizophrenia

2.5. GABAergic Hypothesis of Schizophrenia

2.6. Nicotinic Receptors in Schizophrenia

2.7. The Endocannabinoid System in Schizophrenia

2.8. Role of Inflammation and Oxidative Stress in the Pathomechanism of Schizophrenia

3. Classical Approaches to Treat Schizophrenia

3.1. First-Generation Antipsychotics

3.2. Second-Generation Antipsychotics

3.3. Third-Generation Antipsychotics

4. Targeting Novel GPCR Signaling Mechanisms in Schizophrenia

4.2. Targeting GPCR Signaling Complexity in Schizophrenia

5. Other Non-Classical Approaches for the Treatment of Schizophrenia

6. Conclusions and Future Prospects

Author Contributions

Conflicts of Interest

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