psychiatric case study paranoid schizophrenia

Case Study of Paranoid Schizophrenia in Young Adults

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Introduction: An individual with paranoid schizophrenia exhibits a preoccupation with one or more delusions and experiences frequent auditory hallucinations. This study aimed to describe the diagnosis and treatment of paranoid schizophrenia in young men.

Case presentation: A 20-year-old man was found sitting in the middle of traffic on a bustling route, prompting the cops to transport him to the emergency department for medical care. The patient showed poor personal hygiene during the mental health assessment, appearing dirty and untidy. He constantly paces the examining room, ensuring his back is always against the wall. He exudes a subtle sense of unease with his environment. He characterizes his demeanor as "adequate." Despite his lack of emotional expression, his emotional expression remains constant. The working diagnosis for this patient was paranoid schizophrenia. The patient was prescribed a regimen of atypical antipsychotic medication, specifically risperidone, at a dosage of 2 mg, to be taken twice daily. The treatment will continue for 6 months, with monthly assessments of the patient's symptoms to gauge the medication's effectiveness.

Conclusion: Prior to making a diagnosis of schizophrenia, it is critical to rule out any potential etiologies for the manifestation of psychotic symptoms, such as substance abuse, medication use, or medical conditions. In contrast to prior "typical" antipsychotics such as chlorpromazine and haloperidol, atypical antipsychotics provide a multitude of advantages. Although conventional medications are efficacious in treating the positive symptoms of schizophrenia, they may inadvertently worsen or even induce the negative symptoms.

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The Use of Narrative Therapy on Paranoid Schizophrenia

• Research in progress
• Published: 10 May 2023
• Volume 68 , pages 273–280, ( 2023 )

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• Karina Therese G. Fernandez 1 ,
• Anne Therese Marie B. Martin 1 &
• Dana Angelica S. Ledesma 1  

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Research suggests that a clinical diagnosis of schizophrenia is strongly linked with experiencing negative stereotypes and an inability to recover. In challenging the scientific-logical practice of diagnostic labeling, which totalizes the person’s experience around the illness, Narrative therapy offers a unique approach to treating schizophrenia by putting the spotlight on the client’s values, strengths, and beliefs. This allows the client to discover an alternative life narrative beyond their diagnosis. This study presents a case of a 40-year-old woman with paranoid schizophrenia. She felt that the people in her workplace were out to harm her so she would never work in her field again. At home, she had also begun to question herself as a mother. Narrative therapy techniques such as externalization, thickening the landscape of action and identity, and re-membering were used to aid the client’s recovery and helped her to shift from a problematic view of her identity. The present case focuses on providing steps to guide practitioners in using Narrative therapy for a case where the client has internalized their diagnosis as their identity.

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Dissociative Identity Disorder and Narrative

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Abbreviations

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Acknowledgements

The authors would like to acknowledge the Ateneo Bulatao Center for its constant encouragement and support to advance academic research alongside clinical practice.

The authors did not receive support from any organization for the submitted work.

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Department of Psychology, Ateneo de Manila University, Katipunan Avenue, 1108, Quezon City, Metro Manila, Philippines

Karina Therese G. Fernandez, Anne Therese Marie B. Martin & Dana Angelica S. Ledesma

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All authors contributed to the study. Material preparation, data collection, and analysis were performed by Karina Therese G. Fernandez. The first draft of the manuscript was written by Karina Therese G. Fernandez, Anne Therese Marie B. Martin, and Dana Angelica S. Ledesma. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Karina Therese G. Fernandez .

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The authors have no conflicts of interest to declare that are relevant to the content of this article.

Ethics Approval

This study received ethical approval from the University Research Ethics Office of the Ateneo de Manila University. This research study was conducted retrospectively from data obtained for clinical purposes. A copy of the approval letter has been provided in Appendix A.

Consent to Participate and Publication

In the informed consent given by the Ateneo Bulatao Center for Psychological Services to its therapy clients, there is a very detailed checklist of the extent of how their information can be used. One specific item is “session notes for the purposes of research (paper publications and paper presentations). We have attached a copy of an unsigned informed consent form for reference (see Appendix B).

Informed Consent

By signing an informed consent form, we obtained permission from the client to share her story. Furthermore, her identifying information was changed to ensure confidentiality. Though the informed consent form already covers the consent for data in the therapy sessions to be published, as recommended by informal discussions with members of the University Research Ethics Committee of the Ateneo de Manila University, a second request for informed consent to publish was made after therapy.

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Fernandez, K.T.G., Martin, A.T.M.B. & Ledesma, D.A.S. The Use of Narrative Therapy on Paranoid Schizophrenia. Psychol Stud 68 , 273–280 (2023). https://doi.org/10.1007/s12646-022-00709-z

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Module 11: Schizophrenia Spectrum and Other Psychotic Disorders

Case studies: schizophrenia spectrum disorders, learning objectives.

• Identify schizophrenia and psychotic disorders in case studies

Case Study: Bryant

Thirty-five-year-old Bryant was admitted to the hospital because of ritualistic behaviors, depression, and distrust. At the time of admission, prominent ritualistic behaviors and depression misled clinicians to diagnose Bryant with obsessive-compulsive disorder (OCD). Shortly after, psychotic symptoms such as disorganized thoughts and delusion of control were noticeable. He told the doctors he has not been receiving any treatment, was not on any substance or medication, and has been experiencing these symptoms for about two weeks. Throughout the course of his treatment, the doctors noticed that he developed a catatonic stupor and a respiratory infection, which was identified by respiratory symptoms, blood tests, and a chest X-ray. To treat the psychotic symptoms, catatonic stupor, and respiratory infection, risperidone, MECT, and ceftriaxone (antibiotic) were administered, and these therapies proved to be dramatically effective. [1]

Case Study: Shanta

Shanta, a 28-year-old female with no prior psychiatric hospitalizations, was sent to the local emergency room after her parents called 911; they were concerned that their daughter had become uncharacteristically irritable and paranoid. The family observed that she had stopped interacting with them and had been spending long periods of time alone in her bedroom. For over a month, she had not attended school at the local community college. Her parents finally made the decision to call the police when she started to threaten them with a knife, and the police took her to the local emergency room for a crisis evaluation.

Following the administration of the medication, she tried to escape from the emergency room, contending that the hospital staff was planning to kill her. She eventually slept and when she awoke, she told the crisis worker that she had been diagnosed with attention-deficit/hyperactive disorder (ADHD) a month ago. At the time of this ADHD diagnosis, she was started on 30 mg of a stimulant to be taken every morning in order to help her focus and become less stressed over the possibility of poor school performance.

After two weeks, the provider increased her dosage to 60 mg every morning and also started her on dextroamphetamine sulfate tablets (10 mg) that she took daily in the afternoon in order to improve her concentration and ability to study. Shanta claimed that she might have taken up to three dextroamphetamine sulfate tablets over the past three days because she was worried about falling asleep and being unable to adequately prepare for an examination.

Prior to the ADHD diagnosis, the patient had no known psychiatric or substance abuse history. The urine toxicology screen taken upon admission to the emergency department was positive only for amphetamines. There was no family history of psychotic or mood disorders, and she didn’t exhibit any depressive, manic, or hypomanic symptoms.

The stimulant medications were discontinued by the hospital upon admission to the emergency department and the patient was treated with an atypical antipsychotic. She tolerated the medications well, started psychotherapy sessions, and was released five days later. On the day of discharge, there were no delusions or hallucinations reported. She was referred to the local mental health center for aftercare follow-up with a psychiatrist. [2]

Another powerful case study example is that of Elyn R. Saks, the associate dean and Orrin B. Evans professor of law, psychology, and psychiatry and the behavioral sciences at the University of Southern California Gould Law School.

Saks began experiencing symptoms of mental illness at eight years old, but she had her first full-blown episode when studying as a Marshall scholar at Oxford University. Another breakdown happened while Saks was a student at Yale Law School, after which she “ended up forcibly restrained and forced to take anti-psychotic medication.” Her scholarly efforts thus include taking a careful look at the destructive impact force and coercion can have on the lives of people with psychiatric illnesses, whether during treatment or perhaps in interactions with police; the Saks Institute, for example, co-hosted a conference examining the urgent problem of how to address excessive use of force in encounters between law enforcement and individuals with mental health challenges.

Saks lives with schizophrenia and has written and spoken about her experiences. She says, “There’s a tremendous need to implode the myths of mental illness, to put a face on it, to show people that a diagnosis does not have to lead to a painful and oblique life.”

In recent years, researchers have begun talking about mental health care in the same way addiction specialists speak of recovery—the lifelong journey of self-treatment and discipline that guides substance abuse programs. The idea remains controversial: managing a severe mental illness is more complicated than simply avoiding certain behaviors. Approaches include “medication (usually), therapy (often), a measure of good luck (always)—and, most of all, the inner strength to manage one’s demons, if not banish them. That strength can come from any number of places…love, forgiveness, faith in God, a lifelong friendship.” Saks says, “We who struggle with these disorders can lead full, happy, productive lives, if we have the right resources.”

You can view the transcript for “A tale of mental illness | Elyn Saks” here (opens in new window) .

• Bai, Y., Yang, X., Zeng, Z., & Yang, H. (2018). A case report of schizoaffective disorder with ritualistic behaviors and catatonic stupor: successful treatment by risperidone and modified electroconvulsive therapy. BMC psychiatry , 18(1), 67. https://doi.org/10.1186/s12888-018-1655-5 ↵
• Henning A, Kurtom M, Espiridion E D (February 23, 2019) A Case Study of Acute Stimulant-induced Psychosis. Cureus 11(2): e4126. doi:10.7759/cureus.4126 ↵
• Modification, adaptation, and original content. Authored by : Wallis Back for Lumen Learning. Provided by : Lumen Learning. License : CC BY: Attribution
• A tale of mental illness . Authored by : Elyn Saks. Provided by : TED. Located at : https://www.youtube.com/watch?v=f6CILJA110Y . License : Other . License Terms : Standard YouTube License
• A Case Study of Acute Stimulant-induced Psychosis. Authored by : Ashley Henning, Muhannad Kurtom, Eduardo D. Espiridion. Provided by : Cureus. Located at : https://www.cureus.com/articles/17024-a-case-study-of-acute-stimulant-induced-psychosis#article-disclosures-acknowledgements . License : CC BY: Attribution
• Elyn Saks. Provided by : Wikipedia. Located at : https://en.wikipedia.org/wiki/Elyn_Saks . License : CC BY-SA: Attribution-ShareAlike
• A case report of schizoaffective disorder with ritualistic behaviors and catatonic stupor: successful treatment by risperidone and modified electroconvulsive therapy. Authored by : Yuanhan Bai, Xi Yang, Zhiqiang Zeng, and Haichen Yangcorresponding. Located at : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5851085/ . License : CC BY: Attribution

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Paranoid Schizophrenia and the Paradoxical Path to Paraphrenia and Affectivity – a Case Study

International Journal of Research -GRANTHAALAYAH

Motivation: Analyzing a case of paranoid schizophrenia is a challenge to understand the mechanisms underlying the mind of a schizophrenic. The study became captivating because in the patient's delusional cofabulations there were many fingerprints that the communist period of that time left on the woman's psyche, thus observing the repressions following personal failures that probably led to the current state. Objective: Carrying out an analysis of the life history of a patient with paranoid schizophrenia who, although voluntarily presenting at the hospital, does not recognize her diagnosis and treatment. It presents symptoms that include the delusional ideas of persecution or greatness. It has two possible admissions, currently admitted to the psychiatric department in Bucharest. Results: The patient presents disorders regarding perception, memory, affectivity, observing a disorganized discourse that includes a qualitative perceptual disorder, schizophrenia-specific hypopros...

Related Papers

Iulia-Ioana Enache

Introduction: Disorganized schizophrenia is a subtype of schizophrenia which is not recognized in the updated version of DSM. It is found in ICD-10 with the name of hebephrenic schizophrenia. The paper presents a 27-year-old patient with multiple admissions at psychiatry for schizophrenia with an unknown onset, initially considered to be paranoid; the current level of disorganization of the behavioral acts, of the language, of the thinking, having the intensity of hebephrenic schizophrenia. The paper presents a Ganser syndrome in association with alcohol consumption and prohibited substances use. Methods: hospitalization, psychiatric evaluation under antipsychotic treatment with haloperidol and zuclopenthixol, counseling, social assistance. Results: The patient fulfills all the criteria for the classification in hebephrenic schizophrenia, with a reserved prognosis and an involuntary accentuated potential considering the multiple admissions, the early onset, the lack of social and fa...

IOSR Journals

Background: Chronic paranoid schizophrenia involves over time moments of emotional decompensation, in which the person in question, overlaps manic coloring over all the implicit symptoms of positive, negative dimensions and disorganization. Materials and Methods: The methods used were the initial psychological evaluation, the progressive one, the structured and unstructured clinical interview, psychoanalytic psychotherapy cure, periodical psychiatric evaluation and treatment monitoring, psychoanalytic interpretations, analysis of transference and countertransference dynamics, the transgenerational analysis, the analysis of his social functioning, psychological monitoring, as well as the psychiatric treatment. Results: The present case exposes the psychiatric pathology of a 56-year-old patient, in whom the disease started around the age of 20, the one in question being partially treated. It presents a multiple fragmentary delusional ideation based on pseudo-reminiscences gathered from memories of his youth and cryptomnesia, along with fantastic and dreamy conspiracies. The shift to the affective pole of paranoid schizophrenia is felt from the joviality and exaltation both ideational and emotional. Social functioning is severely affected, the patient losing the coherence of her actions and actions. To these is added the social dimension of the case, the one in question has lost its home and no longer has a social support network. As defense mechanisms from the primitive psychotic register are involved: denial, projection and projective identification, the cleavage of the Self and the Self, found in delusional fragments, in the delusional idea of denying filiation and in the emotional inversion towards the family. Conclusion: Suicidal behavior sometimes occurs in response to hallucinatory commands of self-or hetero-aggression. The risk may increase, being higher immediately after discharge or in the period following a psychotic episode.

Open Journal of Social Sciences

Diana Istrate

Alexandra Militaru

Motivation: A psychiatric patient should be looked at in the longitudinal dynamics of their life because it is possible that during youth, mental suffering has a certain tone to it, which is later erased, transformed or moved, through a greater or lesser contact with the ideas or the affect. Objective: We want to present the life history and dynamics of a subject whose first episode of mental illness of a depressive nature was around the age of 20, and to emphasize how over the years, this nature has faded. Currently, there is an absence of connection between the symptoms and the possible causalities. Material and methods: psychiatric and psychoanalytic interviews in dynamics, analysis of the life map, interpretations, the symptom’s evolution under medication, social support, identification of positive and negative prognostic factors, differential diagnoses, performing the diagnostic tree. Results: The patient presented a first depressive episode in youth with a trigger related to a...

Background: Schizophrenia is characterized by symptoms such as delirium, hallucinations, disorganized behavior, which affects the entire personality. All these symptoms are found in a high-intellect patient, but highly suggestable, which makes the disease more complex, especially over such a long period (20 years). Materials and Methods: The present case presents quasi-psychotic episodes. The present paper aims to evaluate a current profile of a schizophrenia and quasi-psychotic episodes in a 40-year-old patient. The methods that were used are the interview (with both the patient and his father), the observation, the administration of psychological tests and psychiatric treatment. The symptoms specific to a schizophrenia filled with quasi-psychotic episodes are well outlined in the light of disorganized ideas, the presence of certain pseudo reminiscences, the internal reality being distorted by the external one. Results: The patient received treatment to stabilize the mental state that led to a decrease in the delirious ideology, but at some point, the medication was interrupted as a result of his father's decision. Conclusion: There are several factors that affects the social functioning of the patient such as medical treatment unauthorized manipulation, the lack of social support, the non-involvement of the relevant authorities.

Angela Enache

International Journal of Research

NAOMI-EVELINA SOARE

Motivation/Background: Historically speaking, the distinction between manic-depressive disorders and schizophrenia finds itself in an unclear and vast spectrum bordered by the two illnesses. In this paper, we will present a case study that raises a question of diagnosis: bipolar disorder or schizoaffective disorder? Following the description of the symptoms and diagnosis criteria of each of the disorders, along with the personal data of the patient (the ones that are available to us), we will attempt analyzing the case as thoroughly as possible. The paper introduces the case of a 40-year-old woman who presents affective/mood related symptoms. Method: psychiatric evaluation, psychiatric interview, psychodynamic interview and psychodynamic interpretation. Results: The subject has a pathology of attachment developed over a structure with homosexual attachment choices. The multiple psychotraumas of childhood and the busy life history overlap with a vulnerability for emotional manifestat...

Procedia - Social and Behavioral Sciences

Ana-Maria Dragut

Yugashini Paramaswaran

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Giulio Perrotta

The psychotic spectrum is the category that groups together a series of disorders linked to symptomatology in which we witness the fragmentation of the plane of reality until it is completely broken. According to the DSM-V nosography, the disorders under examination are schizophrenia, delusional disorder, paranoid disorder, schizoid disorder, schizotypic disorder, schizoaffective disorder, brief psychotic disorder, psychotic break, and catatonia. In this work, theoretical and practical profiles were analyzed, paying attention to neurobiological content and therapeutic profiles, both psychotherapeutic and psychopharmacological. A note of disappointment has been made in the nosographic categorization of dissociative disorders that currently would not be included in the psychotic spectrum disorders, although from the elements that emerged it would be interesting to revise them, precisely because of the clinical nature of the psychopathological category.

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Paranoid Psychosis: Prevalence And Features

Paranoia is a standalone symptom that may sometimes be associated with certain mental illnesses or mental states. Psychosis is a mental state that frequently causes paranoia, depending on its cause. Exploring paranoia and psychosis in depth may help individuals learn more about how paranoia can be managed and how to find mental health support. 

What is paranoid psychosis? 

Paranoid psychosis is a mental state and cluster of symptoms that can cause anxious thoughts and feelings involving themes of persecution, perceived threats, conspiracy, or imminent threat. While symptoms of paranoia may present in many mental health conditions, they often accompany delusional disorder and other psychotic disorders. 

Anyone can become suspicious of others in certain situations, and in some cases, mistrust may be warranted by an individual's circumstances. However, believing that others intend to harm or interfere with you despite evidence to the contrary can be isolating and detrimental to mental health. A person with paranoid delusions, for example, may hold false beliefs that are difficult to disprove given evidence to the contrary. While some delusions involve paranoia, others do not. In addition, for psychosis to be labeled “paranoia psychosis” other psychotic symptoms must also be present, such as hallucinations and severe delusions. 

Common delusions

A person with paranoid delusions may hold false beliefs that one refuses to dispute despite evidence to the contrary. According to the National Institutes of Health (NIH), the most common delusions involve:

• Delusional jealousy, involving a strong belief that one's partner is unfaithful
• Persecutory delusions relating to themes of being attacked, harassed, impeded from achieving goals, harmed, conspired against, or ridiculed and dismissed
• Grandiosity delusions, involving a sense of being especially important or superior to others, possessing immense and unusual talent, power, knowledge, or skills
• Thought broadcasting delusions related to believing that others can perceive one's thoughts
• Thought insertion delusions, referring to a belief that an exterior source has infiltrated one's mind
• Somatic delusions related to physical sensations and functions, such as believing one has lost control of one's limbs 

A belief must fall outside one's cultural context to be considered a delusion. For example, what may be regarded as an unusual belief in one culture may be widely accepted in another culture or social context. Mental Health America (MHA) lists persecutory delusions and delusions of grandeur as two of the more prevalent delusions. 

Psychotic symptoms

Psychosis is a group of symptoms that affect or distort one's perception of reality. During a psychotic episode, a person may have difficulty perceiving reality as others typically view it. Symptoms may include:

• Delusions: Delusions are firm and false beliefs that are not easily swayed. 
• Hallucinations: Hallucinations are sensory perceptions that are not truly occurring, such as seeing, hearing, or perceiving stimuli others can’t.
• Disorganized behavior: Other symptoms, such as incoherent or nonsensical speech and behavior, may be considered inappropriate by others.

Someone with psychosis might also experience a loss of motivation, confusion, anxiety, and difficulty with daily functioning. 

While psychosis may be experienced by anyone under certain circumstances—often concerning high stress—it often accompanies a mental health condition. Some figures state that psychosis may affect 3.5% of the population, a figure more than three times higher than the diagnosis of schizophrenia. 

Symptoms prior to the onset of psychosis

Before a person develops psychosis , they may experience gradual changes involving:

• Paranoia or suspiciousness
• Challenges with logical thinking 
• Social withdrawal or a desire to spend more time alone
• Unusual feelings, sensations, or ideas
• The absence of emotions 
• Less interest or attention to self-care and hygiene
• Sleep disturbances
• Difficulty with communication
• Reduced performance at school or work
• Challenges differentiating what is real from what is not

Paranoia and psychosis

Paranoia can be considered a feature in some mental health conditions—from schizophrenia spectrum disorders to bipolar disorder and delusional disorder. Characterized as a " key symptom " in psychosis, it may be partially linked to adverse early life experiences and an insecure attachment style. 

Psychosis is not considered a mental health condition in and of itself; instead, it relates to a group of symptoms that may accompany some mental disorders. According to recent findings, borderline personality disorder (BPD) is associated with the highest score on the Brief Symptom Inventory (BSI) in paranoid ideation. Some people with BPD may experience psychosis. However, psychosis is not a criterion for this condition. 

Postnatal psychosis

Postnatal psychosis, also known as puerperal psychosis, can be considered a severe form of postpartum depression or a subtype of brief psychotic disorder that may cause paranoia. According to some figures, it's estimated postnatal psychosis affects one in every 1000 gestational parents. Often, symptoms manifest within the first few days to six weeks following childbirth.

Symptoms of postnatal psychosis may include:

• Delusions, which may involve paranoia about a partner or other caregivers
• Disorientation and confusion
• Difficulty concentrating
• Agitation and difficulty sitting still
• Hallucinations
• Mania or an extremely elevated mood
• Severe mood swings

Factors related to postnatal psychosis

Factors that may contribute to the development of postpartum psychosis include genetic predisposition and previous experience of postpartum psychosis. Sleep disturbances, hormonal changes, and bipolar disorder may also play a significant role. However, psychosis can affect gestational parents without any history of mental illness. 

Seek support from your general practitioner, medical nurse, and those involved in your care if you believe you or someone you know has developed postnatal psychosis. If you’re experiencing postpartum depression and have the urge to harm yourself or your child, please call 988 for immediate support. If you’re looking for peer support, you can contact the Postpartum Support International HelpLine at 1-800-4773 for resources and guidance.

Psychosis and bipolar disorder

The American Psychological Association (APA) characterizes bipolar disorder as "a serious mental illness in which common emotions become intensely and often unpredictably magnified." Bipolar disorder is linked with manic or hypomanic episodes of unusually elevated or irritable moods that interfere with functioning. There are three main types of bipolar disorder: bipolar I disorder, bipolar II disorder, and cyclothymic disorder. 

According to some findings, psychotic symptoms may be considered common in "manic, depressive, and mixed episodes of bipolar disorder." Delusions are associated with bipolar I disorder in connection with mania, where paranoid delusions may be present. 

Paranoid psychosis treatment

Often, the treatment of psychosis involves the use of antipsychotic medication and therapy. One evidence-based approach to treatment that may be recommended is cognitive-behavioral therapy (CBT) to address unhelpful ways of thinking and behaving. 

If you or someone you know are experiencing distressing symptoms, seek a mental health specialist for an evaluation. While there is no definitive diagnosis for psychosis itself, a specialist can discuss your symptoms with you and determine if there's an underlying mental health condition or other causes linked to your experiences. 

Considering therapy

If you or someone you know are at risk for developing psychosis or are experiencing symptoms, seek out a psychiatric evaluation. Seeing a therapist can also be invaluable for finding ways to manage stress and reexamine how situations may be perceived and addressed. 

Online therapy through platforms like BetterHelp can be convenient for those who struggle to access in-person support. On an online platform, you can have sessions with a licensed therapist from your home. You can speak to a therapist via phone, video, or in-app. These options may be helpful when you want a provider to be responsive and convenient to access. Online platforms offer similar modalities to in-person therapy, including CBT. 

One study suggests that "online interventions are both feasible and acceptable for individuals with psychotic disorders and may be effective in assisting with clinical and social outcomes." The same study noted that online therapy is associated with alleviated psychotic symptoms.

Anyone can become mistrustful of others in certain situations, and distrust may be warranted in certain cases. However, believing that others intend to harm you despite evidence to the contrary can be detrimental to mental health. A person with paranoid delusions, for instance, may hold false beliefs that cannot be disproven by evidence to the contrary, causing considerable distress.

Psychosis is a set of symptoms involving hallucinations, delusions, confused thinking patterns, and other experiences. Paranoid psychosis can be described as intense, anxious feelings and thoughts that may include themes of persecution, perceived threats, or conspiracy. While symptoms of paranoia may present in many mental health conditions, they often accompany psychotic disorders. 

If you or someone you know are experiencing distressing symptoms of psychosis, seek out a psychiatric evaluation. Seeing a therapist can also be invaluable for finding ways to manage stress and reexamine how situations may be addressed. Consider reaching out to a provider online or in your area for personalized guidance. 

• Delirium Vs. Psychosis: Symptoms, Similarities, And Differences Medically reviewed by Julie Dodson , MA
• Autism Psychosis: Features Medically reviewed by Melissa Guarnaccia , LCSW
• Relationships and Relations

Case study: treatment-resistant schizophrenia

WELLCOME CENTRE HUMAN NEUROIMAGING/SCIENCE PHOTO LIBRARY

Learning objectives

After reading this article, individuals should be able to:

• Describe the management of schizophrenia;
• Understand pharmaceutical issues that occur during treatment with antipsychotics, especially clozapine ;
• Explain how the Mental Health Act 1983 impacts on care;
• Understand the importance of multidisciplinary and patient-centred care in managing psychosis.

Around 0.5–0.7% of the UK population is living with schizophrenia. Of these individuals, up to one-third are classified as treatment-resistant. This is defined as schizophrenia that has not responded to two different antipsychotics ​[1,2]​ .

Clozapine is the most effective treatment for such patients ​[3]​ . It is recommended by the National Institute for Health and Care Excellence (NICE)[4], and is the only licensed medicine for this patient group ​[4,5]​ . For treatment-responsive patients, there should be a collaborative approach when choosing a treatment ​[4]​ . More information on the recognition and management of schizophrenia can be found in a previous article here , and in accompanying case studies  here . 

This case study aims to explore a patient’s journey in mental health services during a relapse of schizophrenia. It also aims to highlight good practice for communicating with patients with severe mental illness in all settings, and in explaining the role of clozapine. 

Case presentation

Mr AT is a male, aged 26 years, who has been diagnosed with paranoid schizophrenia. He moved to the UK with his family from overseas five years ago. He lives with his parents in a small flat in London. His mother calls the police after he goes missing, finding his past two months’ medication untouched. 

He is found at an airport, attempting to go through security without a ticket. He is confused and paranoid about the police asking him to come with them. 

He is taken to A&E and is medically cleared (see Box 1) ​[6]​ . 

Box 1: Common differentials for psychotic symptoms

Medical conditions can present as psychosis. These include:

• Intoxication/effects of drugs (cannabis, stimulants, opioids, corticosteroids);
• Cerebrovascular disease;
• Temporal lobe epilepsy.

Mr AT’s history is taken by a psychiatrist, and his crisis plan sought (as per NICE recommendations) but he does not have one ​[7]​ .

He has been under the care of mental health services for two years and disputes his diagnosis of paranoid schizophrenia. He was admitted to a psychiatric hospital 18 months ago where he was prescribed the antipsychotic amisulpride at 600mg daily. 

He is teetotal, smokes ten cigarettes a day and smokes cannabis every day. His BMI is 26 and he has hypercholesterolaemia (total cholesterol = 6.1mmol/L, reference range <5mmol/L) but all other tests are normal. 

He has no allergies. His only medication is amisulpride 600mg each morning, which he does not take. 

Medicines reconciliation

Mr AT is transferred to a psychiatric ward and placed under Section 2 of the Mental Health Act , allowing detention for up to 28 days for assessment and treatment (see Box 2).

Box 2: The Mental Health Act 1983

This legislation allows for the detention and treatment of patients with serious mental illness, where urgent care is required. This is often referred to as “sectioning”.

It includes regulations about treatment against a patient’s consent to safeguard patients’ liberty, which become more stringent with longer detentions.

Patients may only be given medication to treat their mental illness without their consent and may refuse physical health treatment. 

He denies any mental illness and tells the team they are conspiring with MI6. He is visibly experiencing auditory hallucinations: seen by him talking to himself and looking to empty corners of the room. Amisulpride is re-prescribed at 300mg, which he declines to take. 

A pharmacy technician completes a medicines reconciliation and contacts the care coordinator. The technician provides information about Mr AT’s treatment and feels he is still unwell as he has continued to express paranoid beliefs about his neighbours and MI6.

The ward pharmacist speaks to the patient. As per NICE guidance on medicines adherence , they adopt a non-judgemental attitude ​[8]​ . Mr AT is provided with information on the benefits and side effects of the medication and is asked open questions regarding his reluctance to take it. For more information on non-adherence to medicines and mental illness, see Box 3 ​[9]​ .

Box 3: Medicines adherence and mental health

Adherence to medication is similar for both physical and mental health medicines: only about 50% of patients are adherent. 

Side effects and lack of involvement in decision making often lead to poor adherence. 

In mental illness, other factors are: 

• Denial of illness (poor ‘insight’); 
• Lack of contact by services;
• Cultural factors, such as family, religious or personal beliefs around mental illness or medication.

Mr AT reports gynaecomastia and impotence, and says that he will not take any antipsychotics as they are “poison designed by MI6”, although is unable to concentrate on the discussion owing to hearing voices. 

He is prescribed clonazepam 1mg twice daily owing to his distress, which is to be reduced as treatment controls his psychosis. He is offered nicotine replacement therapy but decides to use an e-cigarette on the ward. 

He is unable to weigh up information to make decisions owing to his chaotic thinking and is felt to not have capacity to make decisions on his treatment. The team debates what treatment to offer.

Patient preference

Mr AT refuses all options presented to him. A decision is made to administer against his will and aripiprazole is chosen as it is less likely to cause hyperprolactinaemia and sexual dysfunction. He then agrees to take tablets “if it will get me out of hospital”. 

After eight weeks of treatment with orodispersible aripiprazole 15mg, Mr AT is able have a more coherent conversation, but is hallucinating and distressed. He is clearly under treated. The pharmacist attempts to complete a side-effect rating scale ( Glasgow Antipsychotic Side-effect Scale [GASS] ) but he declines. He is pacing around the ward in circles: it is felt he may be experiencing akathisia (restlessness) — a common side effect of antipsychotics (see  Table 1 ). 

Treatment review

The team feels clozapine is the best option owing to the treatment failure of two antipsychotics.  

The team suggests this to Mr AT. He refuses, stating the ward is experimenting on him with new medication and he refuses to take another antipsychotics. 

The pharmacist meets the patient with an occupational therapist to discuss what his goals are. Mr AT states he wants to go to college to become a carpenter. They discuss routes to achieve this, which all involve the first step of leaving hospital and the conclusion that clozapine is the best way to achieve this. The pharmacist clarifies the patient’s aripiprazole will not continue once clozapine is established. They leave information about clozapine with the patient and offer to return to discuss it further. 

Mr AT agrees to take clozapine a week later (see Box 4) ​[10–14]​ . Aripiprazole is tapered and stopped.

Box 4: Clozapine characteristics

Clozapine significantly prolongs life and improves quality of life ​[10]​ . Delaying clozapine is associated with poorer outcomes for patients ​[11]​ . 

Clozapine is under-prescribed owing to healthcare professionals’ anxiety and unfamiliarity around its use ​[12–14]​ .

It causes neutropenia in up to 3% of patients so regular monitoring is required . Twice-weekly monitoring is needed if neutrophils are <2 x10 9 /L. Most patients should stop clozapine if neutrophils are <1.5×10 9 /L. These ranges can differ from some laboratory definitions of neutropenia. 

Other side effects include sedation, hypersalivation and weight gain. See  Table 2  for red flags for serious side effects. 

Clozapine is titrated up slowly to avoid cardiovascular complications. A treatment break of >48 hours warrants specialist advice for a retitration plan. 

The pharmacist meets with Mr AT to discuss clozapine. He is told that this is likely to be a long-term treatment. The pharmacist acknowledges that the patient disagrees with his diagnosis, but this treatment is likely to prevent him from returning to hospital. 

He is started on clozapine at 12.5mg at night, which is slowly increased. Pre- and post-dose monitoring of his vital signs is completed. 

On day nine of the titration, his pulse is 115bpm. He otherwise feels well and blood tests show no signs of myocarditis (see   Table 2), so the titration is continued but slowed.

After 3 weeks he is taking 150mg twice daily of clozapine and his symptoms have significantly improved: he is regularly bathing, not visibly hallucinating and engaging with staff.

The pharmacy technician completes a GASS form. Mr AT reports constipation, hypersalivation and sedation. 

A pharmacist meets the patient to reiterate important counselling points, and discuss questions he may have about his treatment and how to manage side effects. Medication changes are made with the patients’ input: 

• His constipation is monitored with a stool chart and he is started on senna 15mg at night;
• He is started on hyoscine hydrobromide 300 micrograms at night for salivation;
• He is switched to clozapine 300mg once daily at night to simplify his regime and reduce daytime sedation. His clonazepam is reduced and stopped.

Smoking is discussed owing to tobacco’s role as an enzyme inducer (more information on tobacco smoking and its potential drug interactions can be found in a previous article here ). Mr AT states he will continue to use an e-cigarette for now. He is informed that if he starts smoking again, his clozapine may become less effective and he should immediately inform his team. 

He is discharged a few weeks later via a home treatment team and attends a clinic once weekly. On each attendance, he has a full blood count taken and analysed on site. He is assessed by a pharmacy technician and nurse for side effects and adherence to treatment, and his smoking status is clarified. 

The technician asks what he thinks the clozapine has done for him. Mr AT states he is still unsure about having a mental illness, but recognises that clozapine has helped him out of hospital and intends to continue taking it. 

Good practice in the pharmaceutical care of psychosis involves:

• Active patient involvement in discussions on treatment decisions;
• Regular review of treatment: discussing efficacy, side effects and the patient’s view and understanding of treatment; 
• Multidisciplinary approaches to helping patients choose treatment;
• For patients who dispute their diagnosis and the need for treatment, open dialogue is important. Such discussions should involve the patient’s goals, which are likely to be shared by the team (rapid discharge, preventing admissions, reducing distress); 
• Information about treatment should be provided regularly in both written and verbal form;
• Where appropriate, involve carers/next of kin in decision making and information sharing. 

Important points

• Schizophrenia affects 1 in 200 people, meaning such patients will present regularly in all settings;
• Patients with acute psychosis, who are in recovery, may be managed by specialist teams, who are the best source of information for a patient’s care;
• Collaborating with the patient on a viable long-term treatment plan improves adherence;
• Clozapine is recommended where two antipsychotics have failed;
• Clozapine is a high-risk medicine, but the risks are manageable;
• Hydrocarbons produced by smoking (but not nicotine replacement therapy, e-cigarettes or chewing tobacco) induce the enzyme CYP1A2, which reduces clozapine levels markedly (up to 20–60%). Starting or stopping smoking could precipitate relapse or induce toxicity, respectively.
• 1 Conley RR, Kelly DL. Management of treatment resistance in schizophrenia. Biological Psychiatry. 2001; 50 :898–911. doi: 10.1016/s0006-3223(01)01271-9
• 2 Gillespie AL, Samanaite R, Mill J, et al. Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review. BMC Psychiatry. 2017; 17 . doi: 10.1186/s12888-016-1177-y
• 3 Taylor DM. Clozapine for Treatment-Resistant Schizophrenia: Still the Gold Standard? CNS Drugs. 2017; 31 :177–80. doi: 10.1007/s40263-017-0411-6
• 4 Psychosis and schizophrenia in adults: prevention and management. NICE. 2014. https://www.nice.org.uk/guidance/cg178/ (accessed Jan 2022).
• 5 Clozaril 25 mg tablets. Electronic medicines compendium. 2020. https://www.medicines.org.uk/emc/product/4411/smpc (accessed Jan 2022).
• 6 Psychosis and schizophrenia: what else might it be? NICE. 2020. https://cks.nice.org.uk/topics/psychosis-schizophrenia/diagnosis/differential-diagnosis/ (accessed Jan 2022).
• 7 Service user experience in adult mental health: improving the experience of care for people using adult NHS mental health services. NICE. 2011. https://www.nice.org.uk/guidance/cg136/ (accessed Jan 2022).
• 8 Medicines adherence: involving patients in decisions about prescribed medicines and supporting adherence . NICE. 2009. https://www.nice.org.uk/guidance/cg76/ (accessed Jan 2022).
• 9 Taylor D, Barnes T, Young A. The Maudsley Prescribing Guidelines in Psychiatry . 13th ed. Hoboken, New Jersey: : Wiley 2018.
• 10 Meltzer HY, Burnett S, Bastani B, et al. Effects of Six Months of Clozapine Treatment on the Quality of Life of Chronic Schizophrenic Patients. PS. 1990; 41 :892–7. doi: 10.1176/ps.41.8.892
• 11 Üçok A, Çikrikçili U, Karabulut S, et al. Delayed initiation of clozapine may be related to poor response in treatment-resistant schizophrenia. International Clinical Psychopharmacology. 2015; 30 :290–5. doi: 10.1097/yic.0000000000000086
• 12 Whiskey E, Barnard A, Oloyede E, et al. An Evaluation of the Variation and Underuse of Clozapine in the United Kingdom. SSRN Journal. 2020. doi: 10.2139/ssrn.3716864
• 13 Nielsen J, Dahm M, Lublin H, et al. Psychiatrists’ attitude towards and knowledge of clozapine treatment. J Psychopharmacol. 2009; 24 :965–71. doi: 10.1177/0269881108100320
• 14 Verdoux H, Quiles C, Bachmann CJ, et al. Prescriber and institutional barriers and facilitators of clozapine use: A systematic review. Schizophrenia Research. 2018; 201 :10–9. doi: 10.1016/j.schres.2018.05.046
• This article was corrected on 31 January 2022 to clarify that tobacco is an enzyme inducer, not an enzyme inhibitor

Useful structured introduction to the subject for clinical purposes

Thank you Amrit for your feedback, we are pleased that you found this article useful.

Michael Dowdall, Executive Editor, Research & Learning

Please note that smoking causes enzyme INDUCTION not INHIBITION as stated. (Via aromatic polyhydrocarbons, not nicotine)

Hi James. Thank you for bringing this to our attention. This has now been corrected. Hannah Krol, Deputy Chief Subeditor

Only with Herbal formula I was able to cure my schizophrenia Illness with the product I purchase from Dr Sims Gomez Herbs A Clinic in South Africa

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Case study: A patient with severe delusions who self-mutilates

Lesiba t. lebelo.

2 Department of Psychiatry, School of Medicine, University of Pretoria, Pretoria, South Africa

Gerhard P. Grobler

1 Department of Psychiatry, Mamelodi Hospital, Pretoria, South Africa

Associated Data

Data sharing is not applicable to this article as no new data were created or analysed in this study.this study.

Background and introduction

Although some overlapping features exist between self-injury and intention to die, there is growing recognition that non-suicidal self-injury (NSSI), including major self-mutilation (MSM), and suicidal behaviour are distinct entities as evidenced by their significance in terms of aetiology, psychiatric impairment, psychological function, method of self-harm and course or outcome between the two phenomena. 1

We present a case of self-harm in a mental healthcare user diagnosed with schizophrenia to highlight the distinction made above.

Case presentation

Mr X is a 38-year-old, unemployed, single male with no children and with an elementary level of education. This was his index presentation with a 4-year history characterised by ongoing persecutory delusions, as well as auditory hallucinations. He was brought to the Emergency Department by ambulance because he was found to be bleeding profusely from his scrotum in the toilet of a petrol filling station. He alleged that he had cut open his scrotum to remove his testicles before his ‘tormentors’ could do so. He stated clearly that he did not want to die because he valued his life. This was therefore not an attempt at suicide.

He was initially admitted to the urology ward and then referred to psychiatry. The multi-disciplinary team diagnosed him with and treated him for schizophrenia. He responded well to haloperidol 2.5 mg orally in the morning and 5 mg orally at night. A long-acting injectable antipsychotic, flupenthixol decanoate 20 mg intramuscular was also prescribed. No adverse effects were reported. Lorazepam was titrated downwards from 1 mg orally twice daily to 1 mg orally at night, and then stopped before he was discharged. Lansoprazole 30 mg daily orally, tramadol 50 mg three times daily orally and paracetamol 1 g orally were also prescribed as needed.

Upon discharge, on day 44 of the admission, the patient was symptom free with no psychotic or anxiety features.

The patient did not manifest any depressive symptoms throughout his hospitalisation, nor on his 4-week follow-up visit subsequent to discharge. He also demonstrated full and complete understanding that the voices, the self-conviction and his belief that people were coming to harm him were all part of his illness called schizophrenia. He also demonstrated full understanding that the belief of being harmed and people conspiring against him were also part of his schizophrenic illness that had been untreated for at least the past 4 years. With no negative emotion, he demonstrated intellectual understanding with unconditional acceptance of his illness. We emphasised to him that he must be consistent with medical check-ups at his local clinic as some other medical conditions can cause his illness to resurface. It was further emphasised to him that for as long as he took his treatment regularly and as prescribed the schizophrenia would be managed and controlled well. He agreed to stay away from all psychoactive substances. This user was amenable to following up with a clinical psychologist, an occupational therapist and a social worker.

He was followed up 1 month later and then referred to his local clinic for continuation of the prescribed treatment, appointments for continuation of psycho-education, counselling and relevant psycho-therapies. This patient responded well and remitted only on antipsychotic agents.

Literature review and discussion

In a study of measurable variables, paranoia and auditory hallucinations, psychotic-like experience (PLE) and stressful life events all contributed to the patient causing self-harm. Compared to those without PLEs, the prevalence of NSSI was higher than those with PLEs. 1

Psychotic-like experiences are highly prevalent in the general population, with figures of 20% or above being reported in some studies. 1 Major self-mutilation (or NSSI) is a rare but potentially catastrophic complication of severe mental illness. Most people who inflict NSSI have a psychotic disorder, usually a schizophrenia spectrum psychosis. It is not known when in the course of psychotic illness, NSSI is most likely to occur. 2 In general, schizophrenia is associated with worse social functional outcomes compared with other psychotic disorders, but the few studies that directly tested this assumption by comparing the longitudinal courses of social functioning in affective and non-affective psychoses have yielded conflicting findings. 3

Cases of genital self-mutilation reported in the literature have been in patients with psychosis, including schizophrenia. 4 Our own literature review found only a few case reports, published in 1974 (a female patient with schizophrenia and erotomania), 1986 (autocastration with biblical delusions) and in 1995. Greilsheimer writes that: ‘Men who intentionally mutilate or remove their own genitals are likely to be psychotic…’. 5

The reason for presenting the case is that there was no similar case recorded in our country, using Google Scholar search engine database of at least the past 5 years, nor elsewhere when we searched using the following keywords: ‘Self-castration, non-suicidal self-injury and psychosis, self-castration due to psychosis’.

In the South African context, the promulgation of the Traditional Health Practitioners Act no. 35 of 2004 has become an important precipitant for the local review of the place of culture and religion/spirituality in secular areas such as health, mental health and spirituality. 6 Our patient did not display delusions with religious or spiritual content. This particular patient was not practising any religion although he claims to believe in God. He emphasised that he was convinced by his delusions and hallucinations that some people known to him were conspiring to cut his scrotum and extract his testicles for some ritualistic practices. Their psychosis can eventually weaken their faith as they may think that they have been successfully bewitched and cursed even if they have been mentally stabilised.

Patients living with schizophrenia and who suffer persistently high levels of psychotic symptoms as well as poorer (psychosocial) functioning and lower self-esteem have higher severity of suicide behaviour. 7 Even in first episode psychosis, one in 10 people engages in self-harm. 8

It is important to take note of this case as it is the first of its kind and adds to existing knowledge in mental health that untreated and long-standing psychosis can result in the patient harming himself irreversibly such that they lose the capacity to reproduce.

Despite the vulnerable position of the testicles, testicular trauma is relatively uncommon. The mobility of the scrotum may be one reason, severe injury is rare. Given the importance of preserving fertility, traumatic injuries of the testicles deserve careful attention. Testicular injuries can be divided into three broad categories based on the mechanism of injury: (1) blunt trauma, (2) penetrating trauma and (3) degloving trauma. Such injuries are typically seen in males aged 15–40 years.

Our patient was psychotic with auditory hallucinations, persecutory delusions and bizarre delusions which did not include religious delusions when he harmed himself. He was convinced that his ‘tormentors’ were listening to his thoughts and he consequently planned to cut open his scrotum to remove his testicles before they could do that to him. The main reason our patient injured himself was not to die but to relieve himself of the constant and increasing threats of being robbed of his testicles. It is important in the South African context to treat a psychiatric patient by using the multi-disciplinary team approach which is also holistic in nature and covers all aspects of mental healthcare service provision, including spirituality, as most citizens (92%) of South Africa expressed religious affiliation. 9

Not all patients who harm themselves, even severely, are suicidal. Some just want to rid themselves of tormenting psychosis as in this case.

Acknowledgements

The authors wishes to acknowledge their colleagues who supported this project and their patients from whom they learnt much.

Competing interests

The authors have declared that no competing interest exists.

Authors’ contributions

Both authors contributed equally to this work.

Ethical consideration

This article followed all ethical standards for research without direct contact with human or animal subjects.

Funding information

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability statement

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of any affiliated agency of the authors.

How to cite this article: Lebelo LT, Grobler GP. Case study: A patient with severe delusions who self-mutilates. S Afr J Psychiat. 2020;26(0), a1403. https://doi.org/10.4102/sajpsychiatry.v26i0.1403

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Open Access

Peer-reviewed

Research Article

SARS-CoV-2 infection is associated with an increase in new diagnoses of schizophrenia spectrum and psychotic disorder: A study using the US national COVID cohort collaborative (N3C)

Roles Investigation, Software, Writing – original draft

Affiliation Department of Industrial & Management Systems Engineering, West Virginia University, Morgantown, WV, United States of America

Roles Conceptualization, Writing – original draft, Writing – review & editing

Affiliation School of Medicine, West Virginia University, Morgantown, WV, United States of America

Roles Conceptualization, Validation, Writing – review & editing

Roles Data curation, Resources, Software, Visualization

Affiliation Nemours Children’s Health, Jacksonville, FL, United States of America

Roles Conceptualization, Funding acquisition, Methodology, Supervision, Writing – original draft, Writing – review & editing

* E-mail: [email protected]

¶ Membership of the N3C Consortium is listed in the Acknowledgments.

• Asif Rahman, 
• Michael Russell, 
• Wanhong Zheng, 
• Daniel Eckrich, 
• Imtiaz Ahmed, 
• On behalf of the N3C Consortium

• Published: May 30, 2024
• https://doi.org/10.1371/journal.pone.0295891
• Reader Comments

Amid the ongoing global repercussions of SARS-CoV-2, it is crucial to comprehend its potential long-term psychiatric effects. Several recent studies have suggested a link between COVID-19 and subsequent mental health disorders. Our investigation joins this exploration, concentrating on Schizophrenia Spectrum and Psychotic Disorders (SSPD). Different from other studies, we took acute respiratory distress syndrome (ARDS) and COVID-19 lab-negative cohorts as control groups to accurately gauge the impact of COVID-19 on SSPD. Data from 19,344,698 patients, sourced from the N3C Data Enclave platform, were methodically filtered to create propensity matched cohorts: ARDS (n = 222,337), COVID-19 positive (n = 219,264), and COVID-19 negative (n = 213,183). We systematically analyzed the hazard rate of new-onset SSPD across three distinct time intervals: 0-21 days, 22-90 days, and beyond 90 days post-infection. COVID-19 positive patients consistently exhibited a heightened hazard ratio (HR) across all intervals [0-21 days (HR: 4.6; CI: 3.7-5.7), 22-90 days (HR: 2.9; CI: 2.3 -3.8), beyond 90 days (HR: 1.7; CI: 1.5-1.)]. These are notably higher than both ARDS and COVID-19 lab-negative patients. Validations using various tests, including the Cochran Mantel Haenszel Test, Wald Test, and Log-rank Test confirmed these associations. Intriguingly, our data indicated that younger individuals face a heightened risk of SSPD after contracting COVID-19, a trend not observed in the ARDS and COVID-19 negative groups. These results, aligned with the known neurotropism of SARS-CoV-2 and earlier studies, accentuate the need for vigilant psychiatric assessment and support in the era of Long-COVID, especially among younger populations.

Citation: Rahman A, Russell M, Zheng W, Eckrich D, Ahmed I, On behalf of the N3C Consortium (2024) SARS-CoV-2 infection is associated with an increase in new diagnoses of schizophrenia spectrum and psychotic disorder: A study using the US national COVID cohort collaborative (N3C). PLoS ONE 19(5): e0295891. https://doi.org/10.1371/journal.pone.0295891

Editor: Gilbert Sterling Octavius, Universitas Pelita Harapan, INDONESIA

Received: December 2, 2023; Accepted: March 13, 2024; Published: May 30, 2024

Copyright: © 2024 Rahman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: Data cannot be shared publicly because the data resides and remains in the National Center for Advancing Translational Sciences (NCATS) secure cloud-based environment. Investigators who want to access data in the N3C Data Enclave for their research must submit a separate Data Use Request (DUR) for each project they want to establish or join as a collaborator through their institution. Only approved users can analyze data within the N3C platform. Users are allowed to download research results after they are reviewed by a data download committee. Data Website: https://covid.cd2h.org/dashboard/ .

Funding: This study is partly funded by the WVU through their research and scholarship advancement (RSA) grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Introduction

It has been over three years since the initial identification of SARS-CoV-2 infection (hereafter referred to as COVID-19)in the USA. Despite the development of a vaccine and efforts to combat the pandemic, there are still many unanswered questions. Particularly, the long-term effects of COVID-19 on mental health are yet to be fully unwrapped and associated with the disease. Several preliminary studies [ 1 – 3 ] have suggested an increased risk of mental illness following a COVID-19 diagnosis, including but not limited to anxiety, depression, mood disorder, post-traumatic stress disorder (PTSD), insomnia, dementia, delirium, encephalitis, psychosis, and nerve disorder. It is important to note that viral infections resulting from recent outbreaks of severe acute respiratory syndrome (SARS) in 2002 and Middle East respiratory syndrome (MERS) in 2012, both caused by coronavirus closely related to SARS-CoV-2, were also associated with neurological manifestations in some cases [ 3 ].

COVID-19 has a multi-organ pathology that includes the human brain and the central nervous system [ 4 ]. It has been detected both in the brain and cerebrospinal fluids of the diagnosed patients. The COVID-19 patients show a greater cognitive decline compared to the non-COVID patients. It has also been associated with brain structural change [ 5 ]. Recent studies have suggested that more than one-third of the infected individuals develop neurological symptoms in the acute phase of the disease, and around 34% of them show brain abnormalities [ 6 , 7 ]. COVID-19 has been linked to excessive and dysregulated immune responses that can lead to systemic inflammation. Patients with severe COVID-19 have been found to have elevated levels of various inflammatory markers in their blood, such as C-reactive protein (CRP), ferritin, interleukin-6 (IL-6), and others. Among them, higher levels of CRP and IL-6 are linked to a higher risk of different neurological conditions such as major depressive disorders.

It has been well established that a bidirectional interaction exists between the central nervous system, specifically the brain, and systemic inflammation [ 8 ]. In the brain, microglia are the principal cells involved in modulating the effects of remote inflammatory stressors resulting in neuro-inflammatory manifestations of systemic processes arising from multiple causes (trauma, infection, auto-immune processes, etc.) [ 9 ]. Microglial functional and structural alterations have been found in multiple major psychiatric disorders [ 9 – 11 ] although the presence, degree, and configuration of such alterations vary between diagnoses. Therefore, the etiologic and therapeutic significance of these observations remains unclear [ 12 ].

A growing body of literature has implicated systemic inflammation associated with critical illness in the development of delirium [ 13 , 14 ]. In turn, the occurrence of delirium during critical illness is associated with persistent deficits in neurocognitive function following survival [ 15 ]. The presence of pre-exposure decline in cognitive function is associated with an increased risk of post-critical illness persistent neurocognitive disability [ 16 , 17 ]. Differences in epigenetic DNA methylation patterns in critically ill patients with and without delirium have recently been reported [ 18 ]. It is now well established that systemic inflammation affects brain function in critical illness and that these effects are persistent beyond the intensive care episode [ 19 , 20 ]. While the exact mechanisms are still incompletely characterized, epigenetic modification of DNA directed protein transcription may play a potential role.

Major psychiatric illness is known to have a strong genetic component. However, variable penetrance suggests that environmental factors are also important in the development of clinical disease [ 21 ]. Emerging data suggests a significant association between neuroinflammatory changes and major psychiatric illnesses. It has long been speculated that viral infectious illness may have a causative relationship to major psychiatric illness [ 22 – 24 ], especially early in development [ 25 , 26 ]. The strongest associations to date between inflammatory and infectious illness and major psychiatric disease involve the development of schizophrenia, bipolar disorder, and major depression [ 9 , 10 , 27 ]. These associations trace back to the 1918 flu pandemic, which led to the viral hypothesis of schizophrenia. This hypothesis suggests that viral pandemics could result in an increase in SSPD [ 24 ].

Given the increasing evidence demonstrating a link between systemic inflammation generally and viral illness specifically, and subsequent neurocognitive function, the role of neuroinflammation in manifesting major psychiatric disorders and the systemic inflammatory effects of COVID-19, the authors sought to establish if COVID-19 could lead to a rise in the onset of significant psychiatric conditions. We decide to concentrate on the schizophrenia spectrum and psychotic disorders (SSPD), as the data linking inflammatory conditions with the emergence or progression of the disease is most compelling in this context.

We are aware that several studies [ 2 , 3 , 28 ] tried to establish an association between COVID-19 and psychiatric manifestations. However, a significant portion of these studies lacked an appropriate comparison group, leading to an incomplete understanding of the incidence and prevalence of neuro-psychiatric disorders in COVID-19 patients. To address this limitation, our study incorporated a control group comprising individuals with Acute Respiratory Distress Syndrome (ARDS) and those who tested negative for COVID-19. This approach ensured a more precise correlation between COVID-19 and SSPD. Furthermore, we leveraged the N3C platform, utilizing its vast, robust, and long-term data set to effectively discern and quantify the impact of COVID-19 on SSPD.

Materials and methods

This study received written ethical approval from the West Virginia University (WVU) Institutional Review Board (IRB) under protocol number 2201509313. The study qualified under the WVU Flexibility Review Model, as it involves minimal risk and adheres to the Belmont Report’s ethical principles. Approval was granted on April 12, 2022. Our study was a retrospective cohort study. All data was collected from the National COVID-19 Cohort Collaborative (N3C) Data Enclave platform. The dataset was retrieved on May 31, 2023, and we limited our analysis to include only records up to that date. Throughout the process of data collection and subsequent analysis, the authors did not have access to any information that could be used to identify individual participants.

Study design and data collection

To achieve our objectives, we initiated a systematic filtering process as depicted in Fig 1 . Out of an initial dataset of 19 million patients, we categorized them into three primary groups: ARDS, COVID-19 positive, and COVID-19 negative. We applied specific criteria to refine these cohorts. Firstly, we considered only those with a minimum of three visits. Secondly, we excluded patients with any pre-existing mental health conditions and further narrowed down our scope to individuals aged between 17 and 70 years. Notably, within the COVID-19 positive group, we focused on patients characterized by moderate, severe, or terminal outcomes due to the virus. After implementing these filters, our COVID-19 positive cohort size was finalized at 244,226. To ensure that our data from these groups could be directly compared, we also implemented a propensity score matching technique.

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https://doi.org/10.1371/journal.pone.0295891.g001

Three distinct cohorts were constructed for this study: one case and two controls. The case cohort was made up of patients diagnosed with COVID-19, based on the N3C defined computable phenotype version 4.0. [ 29 ]. In order to derive meaningful insights, we limited our COVID-19 positive patients to those with moderate to severe manifestations. This categorization was determined by several factors, including the duration of inpatient hospital stays, usage of invasive ventilation, application of extracorporeal membrane oxygenation (ECMO), and even unfortunate fatalities.

For our controls, we selected patients diagnosed with ARDS post-January 1st, 2020 but without any record of a COVID-19 diagnosis during the pandemic. The third group consisted of those who tested negative for COVID-19 and had no prior history of either COVID-19 or ARDS. The starting population for our study needed to have a history of at least three medical visits spanning 365 days or more. To standardize the timeline across cohorts, index dates were determined based on the earliest date of relevant diagnosis or lab test results.

We excluded individuals below 17 years or over 70 years at the time of the index date. Furthermore, patients with the following mental health disorders prior to the index date were also removed from consideration:

• Schizophrenia Spectrum Disorders
• Bipolar Disorders
• Major Depression
• Personality Disorders

For homogeneity, all cohorts underwent 1:1 nearest neighbor (NN) matching on propensity scores using the R “MatchIt” package. This matching was based on the following attributes:

• Prior psychiatric drug prescription or administration
• Prior Hypothyroidism diagnosis
• Prior Anxiety diagnosis
• Prior Substance Abuse diagnosis
• Prior Insomnia diagnosis

Please refer to the S1 Appendix for specific Observational Medical Outcomes Partnership (OMOP) codesets [ 30 ] used for identifying these attributes. Post-matching, the cohort sizes were 219,264 for COVID-19 positive patients, 213,183 for the lab negatives, and 222,337 for ARDS patients.

Once the cohorts were built, we looked at the first incident post-index date of SSPD. The code sets were developed using the OMOP concept and concept_ancestor tables [ 30 ] and reviewed by subject matter experts. While psychiatry continued to debate over the relationship between psychotic symptoms and mood symptoms [ 31 , 32 ], in this study, to focus on the hallmark thought symptoms characteristic of schizophrenia (such as delusions, hallucinations, or disorganized speech), we separated SSPD from bipolar and depressive disorders. Therefore, while acute psychotic disorder, schizophreniform, schizophrenia, schizoaffective disorders, and related ICD-10 diagnoses were included in the SSPD category, mood disorders with psychotic features were counted in the latter two categories and thus excluded from the analysis.

The data was subsequently structured to include three pivotal columns: a boolean flag denoting whether a patient was diagnosed with SSPD after the index date, the exact date of the patient’s initial SSPD diagnosis post the index date, and the duration in days between the index date and this diagnosis. This data arrangement culminated in a matrix with a single record for each patient, encompassing cohort identifiers, demographic details, other relevant covariates, and the critical outcome variable.

Statistical analysis

To examine the association between COVID-19 and SSPD, we performed a comparative analysis among the matched cohorts using the N3C platform in R (version 4.0). Our primary predictor variable is the disease type, categorized into three groups: COVID-19 positive, COVID-19 negative, and ARDS. The outcome variable is binary, indicating either SSPD or non-SSPD.

We utilized the Cox Proportional Hazard Model [ 33 ] to derive the hazard ratios (HR) of COVID-19 positive patients relative to the COVID-19 negative and ARDS patients. The time-to-event for patients diagnosed with SSPD was measured from their SSPD diagnosis date up to the COVID-19 and ARDS reference dates, which include the dates of their positive COVID test, negative COVID lab test, and ARDS diagnosis. For patients without an SSPD diagnosis, this duration was taken from their most recent recorded visit to the reference date of either their COVID-19 or ARDS diagnosis.

Before deploying the Cox model, it was imperative to test the proportional hazard assumption. In doing so, the Schoenfeld residual analysis, a conventional diagnostic tool for this purpose [ 34 ], yielded a significant p-value. This necessitated rejecting the null hypothesis of a uniform proportional hazard over the comprehensive time frame of 180 days. Consequently, we segmented the cohort into three distinct time intervals: 0–21 days, 22–90 days, and beyond 90 days. These intervals were subsequently validated for the proportional hazard assumptions, and the Cox model was then applied to each to ascertain the hazard ratio (HR).

In tandem with the Cox model, we also conducted the Cochran Mantel Haenszel Test [ 35 ], the Likelihood Ratio Test [ 36 ], the Wald Test [ 35 ], and the Log-rank Test [ 37 ] across the three-time intervals. A p-value threshold of 0.05 served as the determinant for statistical significance in all these tests.

The results shed light on the potential long-term psychiatric implications of SARS-CoV-2 infection. The study found robust evidence linking SARS-CoV-2 infection to an augmented risk of Schizophrenia Spectrum and Psychotic Disorders (SSPD). Specifically, COVID-19 positive patients displayed almost double the incident rate (0.56%) compared to COVID-19 negative (0.33%) and ARDS (0.29%) patients, as showcased in Table 1 .

https://doi.org/10.1371/journal.pone.0295891.t001

Using the Cox model, a marked difference in the hazard ratio of new-onset psychiatric outcomes became evident between COVID-19 positive patients and the cohorts of ARDS and COVID-19 lab negative patients (Please refer to Table 2 ). For all time intervals considered, COVID-19 negative patients were the benchmark for hazard ratio computations. In the immediate 21 days following exposure, the hazard ratio for COVID-19 positive patients was notably high (HR: 4.6; 95% CI: 3.7 to 5.7) when contrasted with ARDS patients (HR: 0.73 CI: 0.53 to 0.99). This suggests that, during the acute phase, individuals positive for COVID-19 were significantly more likely to be diagnosed with SSPD than both their COVID-19 negative and ARDS counterparts.

https://doi.org/10.1371/journal.pone.0295891.t002

In the subsequent interval of 22–90 days, the hazard ratio for COVID-19 positive patients remained elevated (HR: 2.9; 95% CI: 2.3 to 3.8), and interestingly, ARDS patients exhibited their peak hazard ratio of the study (HR:1.1, CI: 0.79 to 1.43). Beyond 90 days, the hazard ratio for the COVID-19 positive group experienced a reduction (HR: 1.7; 95% CI: 1.5 to 1.9) yet was consistently higher than that of the ARDS patients (HR:0.97, CI: 0.86 to 1.47). Despite the reduction in hazard ratios as time progressed, it’s salient to note that COVID-19 survivors remain at a heightened risk for SSPD well beyond the immediate aftermath of their infection. The hazard ratios for different time intervals are visually summarized in Fig 2 .

https://doi.org/10.1371/journal.pone.0295891.g002

Following the detailed hazard ratio analysis, several statistical tests (Please refer to Table 3 ) were conducted to further validate the findings. The Schoenfeld residuals rest returned a p-value exceeding 0.05, suggesting the retention of the null hypothesis that the Hazard Ratio is consistent over time. Additionally, tests such as the Cochran Mantel Haenszel Test, Likelihood Ratio Test, Wald Test, and Log-rank Test consistently showed p-values less than 0.05, reinforcing a significant association between being COVID-19 positive and receiving an SSPD diagnosis.

https://doi.org/10.1371/journal.pone.0295891.t003

In our efforts to determine potential demographic factors influencing SSPD occurrence among COVID-19 positive patients, several key demographics emerged as more susceptible to SSPD following a COVID-19 diagnosis. Specifically, males, individuals aged 21 or younger, those of African American descent, and non-Hispanic or Latino individuals showcased a heightened vulnerability (see Tables 4 and 5 in the S1 Appendix for details). Intriguingly, these same demographic trends, with the exception of the age factor, were mirrored in the SSPD occurrence among both the COVID-19 negative and ARDS groups (refer to Tables 6 and 7 in the S1 Appendix for further insights). While these findings undoubtedly warrant a deeper exploration, we strongly advocate for future research endeavors to prioritize this critical observation regarding the younger people being more susceptible to post-COVID SSPD.

Our study indicates that the likelihood of developing SSPD after a COVID-19 infection is higher than in ARDS and COVID-19-negative patients. The significance of various demographic factors has also emerged from our results. These insights underscore the vital importance of keeping a close watch on the mental well-being of those recovering from COVID-19. Their persistent increased risk points to a wider societal concern, especially regarding severe psychiatric conditions like SSPD.

Extensive literature has accumulated since 2000 that indicates an association between various inflammatory markers, changes in the structure and function of a variety of cellular components of the brain, and the development of major psychiatric illnesses. No longer thought to be “immunologically privileged” by virtue of the blood-brain permeability barrier, it is now well established that the brain is extensively influenced by systemic inflammation and, in turn, can modulate systemic inflammation through descending [ 38 ] and biochemical [ 39 ] pathways. Inflammatory influences in the brain are structural [ 40 ] and functional [ 8 ]. Effects of maternal development on in-utero brain development and subsequent offspring behavior have been demonstrated in animal models [ 41 ] although the relevance to mental illness in humans remains to be determined. Inflammatory influences on the developed brain have also been demonstrated and tied to clinically relevant behavior [ 42 – 44 ]. However, studies evaluating the relationship between various inflammatory markers and clinically relevant behavior have yielded inconsistent results [ 13 , 14 , 45 – 47 ]. At the moment, these inflammatory changes cannot be causally linked directly to specific conditions, but they do provide potential mechanistic insights and may become plausible therapeutic targets in conditions where the response to currently available medications varies widely [ 14 , 40 , 43 ].

With that background, our group sought to establish whether any association existed between SARS-CoV-2 infection and the extensive accompanying inflammatory response and new-onset psychiatric illness. Our results are consistent with the hypothesis that COVID-19 infection and the accompanying inflammatory state (“cytokine storm”) is positively associated with the new onset of SSPD. Further, these results strongly suggest a direct relationship between the development of SSPD and the severity of the disease state and presumably the intensity of the attendant inflammatory response. We acknowledge the viewpoint [ 48 ] that the increase in mental health problems during the COVID-19 pandemic may not stem directly from the virus itself but from indirect consequences of the pandemic, such as isolation, unemployment, and other stress-related factors. It is plausible that receiving a COVID-19 diagnosis, particularly during the pandemic’s early days, could result in considerable psycho-social stress, known to be a risk factor for SSPD. However, in our analysis (see Table 8 in the S1 Appendix ) we have found that the elevated risk of developing SSPD remained consistent over different time periods, from the pandemic’s onset in 2020 through to 2022, a period marked by the availability of vaccines and a gradual return to normalcy. This consistency suggests there might be an underlying link beyond mere psycho-social stress. Our findings also align with previous research that found a higher occurrence of retroviral infection markers in the cerebral spinal fluid and brain tissue of schizophrenia patients compared to non-schizophrenic controls with and without the noninflammatory neurologic disease [ 49 ]. With the demonstrated neurotropism of the SARS-CoV-2 virus [ 50 , 51 ], our results strongly support a potentially causal relationship between COVID-19 infection and new onset SSPD. Long-COVID syndrome, known for causing mild cognitive issues, has been explored for its psychiatric effects. However, smaller studies have yet to establish a clear connection between long-COVID and the onset of major psychiatric conditions [ 52 ]. It’s important to note that our study did not aim to investigate this specific relationship.

The strengths of our study are underscored by the utilization of an expansive and meticulously curated national dataset, enabling an in-depth analysis of a vast number of records. Furthermore, our rigorous approach to defining exclusionary criteria and cohort matching bolster the robustness of our findings. However, the study does possess notable limitations. Foremost among these is, same as any other retrospective studies, the dependence on documented diagnoses (ICD-10 coding) to pinpoint new instances of SSPD. It is conceivable—perhaps even probable—that certain patients might have been inaccurately diagnosed, thereby skewing their categorization as determined by our data extraction methodology. The markedly elevated hazard ratio observed during the acute (0–21 day) phase, for instance, is challenging to rationalize, given that definitive diagnoses for many severe psychiatric conditions, especially SSPD, typically necessitate prolonged periods of behavioral observation. One possible reason might be that many individuals went through an early phase of unnoticed or undeclared symptoms before their clinical visit for COVID-19. When diagnosing SSPD, doctors likely factored in this extended course of symptoms, likely triggered by the brain inflammation caused by the coronavirus infection. There also exists a possibility that some individuals could have experienced acute and transient psychotic disorders (ATPD), which were erroneously identified as SSPD. Delirium, a very common condition in critical illness, could have conceivably been mis-labelled as SSPD, although the characteristics and time course of delirium and SSPD differ significantly making misdiagnosis seemingly less likely. Conversely, patients manifesting early signs hinting at SSPD may have exhibited more distinct symptoms post-COVID-19 infection, subsequently leading to accurate diagnostic coding. Absent direct clinical assessments, pinpointing the primary factor influencing diagnosis remains elusive. Nonetheless, the sustained elevated hazard ratios even beyond the initial 90 days post-infection underscore the continued influence of COVID-19 on the emergence of SSPD.

In this study, we have found a substantial increase in the likelihood of being diagnosed with a schizophrenia spectrum and psychotic disorder (SSPD) after experiencing moderate to severe illness due to SARS-CoV-2 infection, in comparison to a group of individuals who had non-COVID-19 Acute Respiratory Distress Syndrome (ARDS). Our work is consistent with the known neurotropism of the SARS-CoV-2 virus [ 50 , 51 ] and other reports of increased risk of major psychiatric disorders following COVID-19 infection [ 33 , 53 – 55 ]. Further research is required to identify specific characteristics of populations and individuals who may be at a particularly high risk of developing SSPD and potentially other significant psychiatric conditions following COVID-19 infection. Understanding these psychiatric risks associated with COVID-19 is an essential component of our strategy to address the evolving landscape of Long-COVID.

Supporting information

S1 appendix..

https://doi.org/10.1371/journal.pone.0295891.s001

Acknowledgments

We would like to acknowledge West Virginia University (WVU) and West Virginia Clinical & Translational Research Institute (CTSI) for their support. The project described was supported by the National Institute Of General Medical Sciences, 5U54GM104942-04. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

N3C Attribution

The analyses described in this publication were conducted with data or tools accessed through the NCATS N3C Data Enclave ( https://covid.cd2h.org ) and N3C Attribution & Publication Policy v 1.2-2020-08-25b supported by NCATS U24 TR002306. This research was possible because of the patients whose information is included within the data and the organizations ( https://ncats.nih.gov/n3c/resources/data-contribution/data-transfer-agreement-signatories ) and scientists who have contributed to the ongoing development of this community resource [ https://doi.org/10.1093/jamia/ocaa196 ].

Disclaimer The N3C Publication Committee confirmed that this manuscript MSID:1645.616 is in accordance with N3C data use and attribution policies; however, this content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the N3C program.

The N3C data transfer to NCATS is performed under a Johns Hopkins University Reliance Protocol # IRB00249128 or individual site agreements with NIH. The N3C Data Enclave is managed under the authority of the NIH; information can be found at https://ncats.nih.gov/n3c/resources .

Individual Acknowledgements For Core Contributors

We gratefully acknowledge the following core contributors to N3C:

Adam B. Wilcox, Adam M. Lee, Alexis Graves, Alfred (Jerrod) Anzalone, Amin Manna, Amit Saha, Amy Olex, Andrea Zhou, Andrew E. Williams, Andrew Southerland, Andrew T. Girvin, Anita Walden, Anjali A. Sharathkumar, Benjamin Amor, Benjamin Bates, Brian Hendricks, Brijesh Patel, Caleb Alexander, Carolyn Bramante, Cavin Ward-Caviness, Charisse Madlock-Brown, Christine Suver, Christopher Chute, Christopher Dillon, Chunlei Wu, Clare Schmitt, Cliff Takemoto, Dan Housman, Davera Gabriel, David A. Eichmann, Diego Mazzotti, Don Brown, Eilis Boudreau, Elaine Hill, Elizabeth Zampino, Emily Carlson Marti, Emily R. Pfaff, Evan French, Farrukh M Koraishy, Federico Mariona, Fred Prior, George Sokos, Greg Martin, Harold Lehmann, Heidi Spratt, Hemalkumar Mehta, Hongfang Liu, Hythem Sidky, J.W. Awori Hayanga, Jami Pincavitch, Jaylyn Clark, Jeremy Richard Harper, Jessica Islam, Jin Ge, Joel Gagnier, Joel H. Saltz, Joel Saltz, Johanna Loomba, John Buse, Jomol Mathew, Joni L. Rutter, Julie A. McMurry, Justin Guinney, Justin Starren, Karen Crowley, Katie Rebecca Bradwell, Kellie M. Walters, Ken Wilkins, Kenneth R. Gersing, Kenrick Dwain Cato, Kimberly Murray, Kristin Kostka, Lavance Northington, Lee Allan Pyles, Leonie Misquitta, Lesley Cottrell, Lili Portilla, Mariam Deacy, Mark M. Bissell, Marshall Clark, Mary Emmett, Mary Morrison Saltz, Matvey B. Palchuk, Melissa A. Haendel, Meredith Adams, Meredith Temple-O'Connor, Michael G. Kurilla, Michele Morris, Nabeel Qureshi, Nasia Safdar, Nicole Garbarini, Noha Sharafeldin, Ofer Sadan, Patricia A. Francis, Penny Wung Burgoon, Peter Robinson, Philip R.O. Payne, Rafael Fuentes, Randeep Jawa, Rebecca Erwin-Cohen, Rena Patel, Richard A. Moffitt, Richard L. Zhu, Rishi Kamaleswaran, Robert Hurley, Robert T. Miller, Saiju Pyarajan, Sam G. Michael, Samuel Bozzette, Sandeep Mallipattu, Satyanarayana Vedula, Scott Chapman, Shawn T. O'Neil, Soko Setoguchi, Stephanie S. Hong, Steve Johnson, Tellen D. Bennett, Tiffany Callahan, Umit Topaloglu, Usman Sheikh, Valery Gordon, Vignesh Subbian, Warren A. Kibbe, Wenndy Hernandez, Will Beasley, Will Cooper, William Hillegass, Xiaohan Tanner Zhang. Details of contributions are available at https://covid.cd2h.org/core-contributors

Data Partners with Released Data

The following institutions whose data is released or pending:

Available: Advocate Health Care Network—UL1TR002389: The Institute for Translational Medicine (ITM) • Aurora Health Care Inc—UL1TR002373: Wisconsin Network For Health Research • Boston University Medical Campus—UL1TR001430: Boston University Clinical and Translational Science Institute • Brown University—U54GM115677: Advance Clinical Translational Research (Advance-CTR) • Carilion Clinic—UL1TR003015: iTHRIV Integrated Translational health Research Institute of Virginia • Case Western Reserve University—UL1TR002548: The Clinical & Translational Science Collaborative of Cleveland (CTSC) • Charleston Area Medical Center—U54GM104942: West Virginia Clinical and Translational Science Institute (WVCTSI) • Children’s Hospital Colorado—UL1TR002535: Colorado Clinical and Translational Sciences Institute • Columbia University Irving Medical Center—UL1TR001873: Irving Institute for Clinical and Translational Research • Dartmouth College—None (Voluntary) Duke University—UL1TR002553: Duke Clinical and Translational Science Institute • George Washington Children’s Research Institute—UL1TR001876: Clinical and Translational Science Institute at Children’s National (CTSA-CN) • George Washington University—UL1TR001876: Clinical and Translational Science Institute at Children’s National (CTSA-CN) • Harvard Medical School—UL1TR002541: Harvard Catalyst • Indiana University School of Medicine—UL1TR002529: Indiana Clinical and Translational Science Institute • Johns Hopkins University—UL1TR003098: Johns Hopkins Institute for Clinical and Translational Research • Louisiana Public Health Institute—None (Voluntary) • Loyola Medicine—Loyola University Medical Center • Loyola University Medical Center—UL1TR002389: The Institute for Translational Medicine (ITM) • Maine Medical Center—U54GM115516: Northern New England Clinical & Translational Research (NNE-CTR) Network • Mary Hitchcock Memorial Hospital & Dartmouth Hitchcock Clinic—None (Voluntary) • Massachusetts General Brigham—UL1TR002541: Harvard Catalyst • Mayo Clinic Rochester—UL1TR002377: Mayo Clinic Center for Clinical and Translational Science (CCaTS) • Medical University of South Carolina—UL1TR001450: South Carolina Clinical & Translational Research Institute (SCTR) • MITRE Corporation—None (Voluntary) • Montefiore Medical Center—UL1TR002556: Institute for Clinical and Translational Research at Einstein and Montefiore • Nemours—U54GM104941: Delaware CTR ACCEL Program • NorthShore University HealthSystem—UL1TR002389: The Institute for Translational Medicine (ITM) • Northwestern University at Chicago—UL1TR001422: Northwestern University Clinical and Translational Science Institute (NUCATS) • OCHIN—INV-018455: Bill and Melinda Gates Foundation grant to Sage Bionetworks • Oregon Health & Science University—UL1TR002369: Oregon Clinical and Translational Research Institute • Penn State Health Milton S. Hershey Medical Center—UL1TR002014: Penn State Clinical and Translational Science Institute • Rush University Medical Center—UL1TR002389: The Institute for Translational Medicine (ITM) • Rutgers, The State University of New Jersey—UL1TR003017: New Jersey Alliance for Clinical and Translational Science • Stony Brook University—U24TR002306 • The Alliance at the University of Puerto Rico, Medical Sciences Campus—U54GM133807: Hispanic Alliance for Clinical and Translational Research (The Alliance) • The Ohio State University—UL1TR002733: Center for Clinical and Translational Science • The State University of New York at Buffalo—UL1TR001412: Clinical and Translational Science Institute • The University of Chicago—UL1TR002389: The Institute for Translational Medicine (ITM) • The University of Iowa—UL1TR002537: Institute for Clinical and Translational Science • The University of Miami Leonard M. Miller School of Medicine—UL1TR002736: University of Miami Clinical and Translational Science Institute • The University of Michigan at Ann Arbor—UL1TR002240: Michigan Institute for Clinical and Health Research • The University of Texas Health Science Center at Houston—UL1TR003167: Center for Clinical and Translational Sciences (CCTS) • The University of Texas Medical Branch at Galveston—UL1TR001439: The Institute for Translational Sciences • The University of Utah—UL1TR002538: Uhealth Center for Clinical and Translational Science • Tufts Medical Center—UL1TR002544: Tufts Clinical and Translational Science Institute • Tulane University—UL1TR003096: Center for Clinical and Translational Science • The Queens Medical Center—None (Voluntary) • University Medical Center New Orleans—U54GM104940: Louisiana Clinical and Translational Science (LA CaTS) Center • University of Alabama at Birmingham—UL1TR003096: Center for Clinical and Translational Science • University of Arkansas for Medical Sciences—UL1TR003107: UAMS Translational Research Institute • University of Cincinnati—UL1TR001425: Center for Clinical and Translational Science and Training • University of Colorado Denver, Anschutz Medical Campus—UL1TR002535: Colorado Clinical and Translational Sciences Institute • University of Illinois at Chicago—UL1TR002003: UIC Center for Clinical and Translational Science • University of Kansas Medical Center—UL1TR002366: Frontiers: University of Kansas Clinical and Translational Science Institute • University of Kentucky—UL1TR001998: UK Center for Clinical and Translational Science • University of Massachusetts Medical School Worcester—UL1TR001453: The UMass Center for Clinical and Translational Science (UMCCTS) • University Medical Center of Southern Nevada—None (voluntary) • University of Minnesota—UL1TR002494: Clinical and Translational Science Institute • University of Mississippi Medical Center—U54GM115428: Mississippi Center for Clinical and Translational Research (CCTR) • University of Nebraska Medical Center—U54GM115458: Great Plains IDeA-Clinical & Translational Research • University of North Carolina at Chapel Hill—UL1TR002489: North Carolina Translational and Clinical Science Institute • University of Oklahoma Health Sciences Center—U54GM104938: Oklahoma Clinical and Translational Science Institute (OCTSI) • University of Pittsburgh—UL1TR001857: The Clinical and Translational Science Institute (CTSI) • University of Pennsylvania—UL1TR001878: Institute for Translational Medicine and Therapeutics • University of Rochester—UL1TR002001: UR Clinical & Translational Science Institute • University of Southern California—UL1TR001855: The Southern California Clinical and Translational Science Institute (SC CTSI) • University of Vermont—U54GM115516: Northern New England Clinical & Translational Research (NNE-CTR) Network • University of Virginia—UL1TR003015: iTHRIV Integrated Translational health Research Institute of Virginia • University of Washington—UL1TR002319: Institute of Translational Health Sciences • University of Wisconsin-Madison—UL1TR002373: UW Institute for Clinical and Translational Research • Vanderbilt University Medical Center—UL1TR002243: Vanderbilt Institute for Clinical and Translational Research • Virginia Commonwealth University—UL1TR002649: C. Kenneth and Dianne Wright Center for Clinical and Translational Research • Wake Forest University Health Sciences—UL1TR001420: Wake Forest Clinical and Translational Science Institute • Washington University in St. Louis—UL1TR002345: Institute of Clinical and Translational Sciences • Weill Medical College of Cornell University—UL1TR002384: Weill Cornell Medicine Clinical and Translational Science Center • West Virginia University—U54GM104942: West Virginia Clinical and Translational Science Institute (WVCTSI)• Submitted: Icahn School of Medicine at Mount Sinai—UL1TR001433: ConduITS Institute for Translational Sciences • The University of Texas Health Science Center at Tyler—UL1TR003167: Center for Clinical and Translational Sciences (CCTS) • University of California, Davis—UL1TR001860: UCDavis Health Clinical and Translational Science Center • University of California, Irvine—UL1TR001414: The UC Irvine Institute for Clinical and Translational Science (ICTS) • University of California, Los Angeles—UL1TR001881: UCLA Clinical Translational Science Institute • University of California, San Diego—UL1TR001442: Altman Clinical and Translational Research Institute • University of California, San Francisco—UL1TR001872: UCSF Clinical and Translational Science Institute • Pending: Arkansas Children’s Hospital—UL1TR003107: UAMS Translational Research Institute • Baylor College of Medicine—None (Voluntary) • Children’s Hospital of Philadelphia—UL1TR001878: Institute for Translational Medicine and Therapeutics • Cincinnati Children’s Hospital Medical Center—UL1TR001425: Center for Clinical and Translational Science and Training • Emory University—UL1TR002378: Georgia Clinical and Translational Science Alliance • HonorHealth—None (Voluntary) • Loyola University Chicago—UL1TR002389: The Institute for Translational Medicine (ITM) • Medical College of Wisconsin—UL1TR001436: Clinical and Translational Science Institute of Southeast Wisconsin • MedStar Health Research Institute—None (Voluntary) • Georgetown University—UL1TR001409: The Georgetown-Howard Universities Center for Clinical and Translational Science (GHUCCTS) • MetroHealth—None (Voluntary) • Montana State University—U54GM115371: American Indian/Alaska Native CTR • NYU Langone Medical Center—UL1TR001445: Langone Health’s Clinical and Translational Science Institute • Ochsner Medical Center—U54GM104940: Louisiana Clinical and Translational Science (LA CaTS) Center • Regenstrief Institute—UL1TR002529: Indiana Clinical and Translational Science Institute • Sanford Research—None (Voluntary) • Stanford University—UL1TR003142: Spectrum: The Stanford Center for Clinical and Translational Research and Education • The Rockefeller University—UL1TR001866: Center for Clinical and Translational Science • The Scripps Research Institute—UL1TR002550: Scripps Research Translational Institute • University of Florida—UL1TR001427: UF Clinical and Translational Science Institute • University of New Mexico Health Sciences Center—UL1TR001449: University of New Mexico Clinical and Translational Science Center • University of Texas Health Science Center at San Antonio—UL1TR002645: Institute for Integration of Medicine and Science • Yale New Haven Hospital—UL1TR001863: Yale Center for Clinical Investigation.

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