case studies about schizophrenia

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• J Family Med Prim Care
• v.7(6); Nov-Dec 2018

Very early-onset psychosis/schizophrenia: Case studies of spectrum of presentation and management issues

Jitender aneja.

1 Department of Psychiatry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

Kartik Singhai

Karandeep paul.

Schizophrenia occurs very uncommonly in children younger than 13 years. The disease is preceded by premorbid difficulties, familial vulnerability, and a prodromal phase. The occurrence of positive psychotic symptoms such as delusions and hallucinations depends on the level of cognitive development of child. Furthermore, at times it is very difficult to differentiate the psychopathology and sustain a diagnosis of schizophrenia in view of similarities with disorders such as autism, mood disorders, and obsessive compulsive disorders. Here, we present three case studies with varying presentation of childhood-onset psychosis/schizophrenia and associated management issues.

Introduction

Schizophrenia is a chronic severe mental illness with heterogeneous clinical profile and debilitating course. Research shows that clinical features, severity of illness, prognosis, and treatment of schizophrenia vary depending on the age of onset of illness.[ 1 , 2 ] Hence, age-specific research in schizophrenia has been emphasized. Although consistency has been noted in differentiating early-onset psychosis (onset <18 years of age) and adult-onset psychosis (onset >18 years), considerable variation is observed with regard to the age of childhood-onset schizophrenia or very early-onset psychosis/schizophrenia (VEOP/VEOS).[ 2 , 3 ] Most commonly, psychosis occurring at <13 years of age has been considered to be of very early onset and that between 13 and 17 years to be of adolescent onset.[ 4 ] Furthermore, VEOS has been considered to be rare and shown to have differing clinical features (including positive and negative symptoms, cognitive decline, and neuroimaging findings), course, and outcome when compared with that of early-onset or adult-onset schizophrenia.[ 3 ] Progress in acknowledgement of psychotic disorders in children in the recent times has led primary care physicians and paediatricians to increasingly serve as the principal identifiers of psychiatrically ill youth. In recent years, there has been substantial research in early intervention efforts (e.g., with psychotherapy or antipsychotic medicines) focused on the early stages of schizophrenia and on young people with prodromal symptoms.[ 5 ] Here, we report a series of cases with very early onset of psychosis/schizophrenia who had varying clinical features and associated management issues.

Case Reports

A 14-year-old boy, educated up to class 6, belonging to a family of middle socioeconomic status and residing in an urban area was brought with complaints of academic decline since 3 years and hearing voices for the past 2 years. The child was born out of a nonconsanguineous marriage, an unplanned, uneventful, but wanted pregnancy. The child attained developmental milestones as per age. From his early childhood, he was exposed to aggressive behavior of his father, who often attempted to discipline him and in this pursuit at times was abusive and aggressive toward him. Marital problems and domestic violence since marriage lead to divorce of parents when the child attained age of 10 years.

The following year, the child and the mother moved to maternal grandparents’ home and his school was also changed. Within a year of this, a decline in his academic performance with handwriting deterioration, and irritable and sad behaviour was noted. Complaints from school were often received by the mother where the child was found engaged in fist fights and undesirable behavior. He also preferred solitary activities and resented to eat with the rest of the family. In addition, a decline in performance of daily routine activities was seen. No history suggestive of depressive cognitions at that time was forthcoming. A private psychiatrist was consulted who treated him with sodium valproate up to 400 mg/day for nearly 2 months which led to a decline in his irritability and aggression. But the diagnosis was deferred and the medications were gradually tapered and stopped. Over the next 1 year, he also started hearing voices that fulfilled dimensions of commanding type of auditory hallucinations. He suspected that family members including his mother collude with the unknown persons, whose voices he heard and believed it was done to tease him. He eventually dropped out of school and was often found awake till late night, seen muttering to self, shouting at persons who were not around with further deterioration in his socialization and self-care. Another psychiatrist was consulted and he was now diagnosed with schizophrenia and treated inpatient for 2 weeks with risperidone 3 mg, olanzapine 2.5 mg, and oxcarbazepine 300 mg/day with some improvement in his symptoms. Significant weight gain with the medication lead to poor compliance which further led to relapse within 3 months of discharge. Frequent aggressive episodes over the next 1 year resulted in multiple hospital admissions. He was brought to us with acute exacerbation of symptoms and was receiving divalproex sodium 1500 mg/day, aripiprazole 30 mg/day, trifluperazine 15 mg/day, olanzapine 20 mg/day, and lorazepam injection as and when required. He was admitted for diagnostic clarification and rationalization of his medications. He had remarkable physical features of elongated face with large ears. Non-cooperation for mental state examination, and aggressive and violent behavior were noted. He was observed to be muttering and laughing to self. His mood was irritable, speech was laconic, and he lacked insight into his illness. We entertained a diagnosis of very early-onset schizophrenia and explored for the possibilities of organic psychosis, autoimmune encephalitis, and Fragile X syndrome. The physical investigations done are shown in Table 1 . Further special investigations in the form of rubella antibodies (serum IgG = 64.12 U/mL, IgM = 2.44 U/mL) and polymerase chain reaction for Fragile X syndrome (repeat size = 24) were normal. His intelligence quotient measured a year ago was 90, but he did not cooperate for the same during present admission. Initially, we reduced the medication and only kept him on aripiprazole 30 mg/day and added lurasidone 40 mg twice a day and discharged him with residual negative symptoms only. However, his hallucinations and aggression reappeared within 2 weeks of discharge and was readmitted. This time eight sessions of bilateral modified electroconvulsive therapy were administered and he was put on aripiprazole 30 mg/day, chlorpromazine 600 mg/day, sodium divalproex 1000 mg/day, and trihexyphenidyl 4 mg/day. The family was psychoeducated about the illness, and mother's expressed emotions and overinvolvement was addressed by supportive psychotherapy. Moreover, an activity schedule for the child was made, and occupational therapy was instituted. Dietary modifications in view of weight gain were also suggested. In the past 6 months, no episodes of violence came to our notice, though irritability on not meeting his demands is persistent. However, poor socialization, lack of motivation, apathy, weight gain subsequent to psychotropic medications, and aversion to start school are still unresolved. Influence of his multiple medications on bone marrow function is an impending issue of concern.

Details of investigations done in the three children

An 11-year-old boy, educated up to class 3, belonging to a rural family of lower socioeconomic status was brought with complaints of academic decline since 2 years, repetition of acts, irritability since a year, and adoption of abnormal postures since 6 months. He was born out of a nonconsanguineous marriage, uneventful birth, and pregnancy. He was third in birth order and achieved developmental milestones at an appropriate age. Since 2 years, he would not attend to his studies, had poor attention, and difficult memorization. He attributed it to lack of friends at school and asked for school change. There was no history of low mood, depressive cognitions, conduct problems, or bullying and he performed his daily routine like his premorbid self at that time. Since a year, he was observed to repeat certain acts such as pacing in the room from one end to another, continuously for up to 1–2 h, with intermittent stops and often insisted his mother to follow the suit, stand nearby him, or else he would clang on her. He prohibited other family members except his mother near him and would accept his meals only from her. He repeatedly sought assurance of his mother if he had spoken everything right. He also washed his hands repeatedly, up to 10–20 times at one time, and was unable to elaborate reason for the same. His mood during that period was largely irritable with no sadness or fearfulness. He mostly wore the same set of clothes, would be forced to take bath or get nails/hair trimmed, and efforts to these were often met with aggression from the patient. Eventually, he stopped going to school and his family sought faith healing. Within the next 5–6 months, his illness worsened. Fixed gaze, reduced eye blinking, smiling out of context, diminished speech, and refusal to eat food were the reasons for which he was brought to us. His physical examination was unremarkable and his mental state examination using the Kirby's method showed an untidy and ill-kempt child, with infrequent spontaneous acts, and occasional resentment for examination. He had an expressionless face, with occasional smiling to self, negativism, and mutism. No rigidity in any of the limb was observed. He was diagnosed with catatonic schizophrenia and probable obsessive compulsive disorder (vs mannerisms). We performed a battery of physical investigation to rule out organic psychosis [ Table 1 ]. He responded to injection lorazepam with which catatonia melted away. He was also prescribed olanzapine up to 15 mg/day, fluoxetine 20 mg/day, and dietary modification and lactulose for constipation. The family left against medical advice with 50%–60% clinical improvement [rating on Bush Francis Catatonia Rating scale (BFCRS) reduced from 10 to 4]. He relapsed within a month of discharge, initially with predominance of the probable obsessive compulsive symptoms. Fluoxetine was further increased to up to 60 mg/day. But within the next 2 months, the catatonic symptoms reappeared and he was readmitted. He had received olanzapine up to 25 mg/day, which was replaced with risperidone. In view of nonresponse to intravenous lorazepam, we administered him five sessions of modified bilateral Electro-convulsive therapy (ECT) (rating on BFCRS reduced from 8 to 0). The family was psychoeducated about the child's illness and the need for continuous treatment was emphasized. He was discharged with up to 80%–90% improvement. At follow-ups, he started participating at farm work of the family, took care of self, with some repetition of acts such as washing of hands, and denied any associated anxiety symptoms. However, efforts to re-enroll in school had been futile as the child did not agree for it. He has been maintaining at the same level since 6 months of discharge.

A 7-year-old girl, student of second class, belonging to a high socioeconomic status family living in an urban locality was brought with complaints of academic decline, irritability, and abnormal behavior for the past 9 months. The child was born out of a nonconsanguineous marriage, is first in order, and was a wanted child. Maternal health during pregnancy was normal, but the period of labor was prolonged beyond 18 h, so a lower segment caesarean section was performed. There was no history of birth-related complications and the child's birth weight was 2.80 kg. The child attained developmental milestones as per age. The child had a temperament characterized by high activity levels, below average threshold of distractibility, average ability to sustain attention and persist, easy to warm up, adaptation to new situations, and regular bowel and bladder habits. She was enrolled in school at the age of 4 years and progressed well till 9 months back when a decline in her academic interest was observed by her class teacher. Deterioration of her handwriting skills and avoidance of group activities in school were observed. Similarly, at home persistent irritable behavior was seen and her play activities with her siblings reduced. However, her biofunctions were normal during this period.

One month prior to visiting us, she started insisting on wearing the same dress. She wore the same colored or at times the same dress which she would not take off even at bed or bath time. In addition, a change in her mood from largely irritable to cheerful was noted. Her activity levels were increased and it would be difficult to make her sit quietly in class. Her speech output was more than her usual self and she talked incessantly. Her sleep duration also decreased and she started getting up 3–4 h earlier than her usual routine. In view of these symptoms, her family made first contact with us. Her physical examination was normal and mental state examination revealed her to be cheerful, overactive, and difficult to interrupt. She sang and danced during the interview. We diagnosed her with acute mania on the basis of clinical evaluation and assessment on MINI Kid 6.0.[ 6 ] The details of her physical examination are depicted in Table 1 . She was initially treated with olanzapine 5 mg/day which was later on increased to 10 mg/day. However, no response was observed with it in the next 2 weeks, so it was cross tapered with sodium valproate which was built up to 400 mg/day. She improved by nearly 50%, but her mood still remained cheerful/irritable. She did not resume her school and was brought irregularly for the follow-up. Within the next 2 months, she also started muttering to herself and made certain abnormal gestures. She often feared staying alone, or while going to bed insisted the lights to be kept on and ask someone to accompany her in the toilet unlike her previous self. When asked, she reported seeing a lady in white clothes, with no other details. She stopped asking for food on her own and remained lost in her fantasy world. However, her interest in dressing and appreciating herself in mirror persisted. Her mood during this period was mostly labile and often changed from cheerful to sad or irritable. As per the family, the medications were continued as advised. So in view of the emerging picture, the diagnosis was revised to schizo-affective disorder, and in addition to hike in dose of sodium valproate to 500 mg/day, risperidone 2 mg/day was also added. However, even after 8 weeks of treatment with this combination with hike of risperidone to 4 mg/day, there was no relief. The child is still symptomatic, does not go to school, and has significant dysfunction. Psychosocial intervention in the form of psychoeducation, activity scheduling for the child, and occupational therapy has been instituted in addition to the existing treatment regimen, but results are yet to be seen.

The older concept of neurodegenerative etiology of schizophrenia has been superseded by evolving neurodevelopmental nature of this disease. The latter has been attributed to initiation of the underlying pathophysiological processes long before the onset of clinical disease and interaction of the various genetic and environmental factors. The more accommodating theorist propose schizophrenia to be of neurodevelopmental in origin which in turn speeds the process of neurodegeneration.

On clinical front, VEOS is associated with a more insidious onset, prominent negative symptoms, auditory hallucinations, poorly formed delusions which is in part due to less developed cognitive abilities.[ 7 ] The presence of history of speech and language delay as well as motor development deficits have been observed in major studies on childhood-onset schizophrenia, be it the Maudsley early-onset schizophrenia project or the NIMH study.[ 8 , 9 ] Premorbid deficits in social adjustments and presence of autistic symptoms have also been shown. Moreover, the early onset of psychosis is associated with poor prognosis, worse overall functioning, and multiple hospitalizations.[ 7 ] The duration of untreated psychosis in childhood-onset psychosis has been shown to be smaller in hospital-based studies[ 10 ] and larger in community settings.[ 11 ] In addition, the presence of comorbidities and an organic etiology or history of maternal illness during pregnancy is a common finding in VEOS.[ 10 ] In addition, obsessive compulsive symptoms are frequently observed in first-episode drug-naive schizophrenia patients and have a poorer outcome, more severe impairment of social behavior, and lower functioning.[ 12 ] However, in many instances it is very difficult to differentiate the obsessive compulsive symptoms from the motor symptoms of schizophrenia such as stereotypy and mannerisms and varying degree of insight.[ 13 ]

In the present case series, all the children had an insidious onset of illness, with initial symptom of academic decline, and poorly formed psychotic symptoms/psychotic-like experiences. All the children reported here had dropped out of school, showed a shift in their interests, withdrew from social circle, appeared to be distant, had impaired self-care, and often lacked concern for others along with a range of mood disturbances. All these symptoms fit into the classical description of prodromal symptoms of schizophrenia.[ 14 ] In contrast to available evidence, no history of motor, speech, or language delay was noted in any of the child. Furthermore, no history suggestive of autistic features or problems in social adjustments prior to onset of illness was forthcoming.

However, the diagnosis of schizophrenia could be clearly made in the first case, while the second child had predominant catatonic and probably obsessive compulsive symptoms. It is difficult to ascertain the diagnosis of schizophrenia on the basis of presence of only catatonic symptoms and no delusions and hallucinations or negative symptoms as required by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition or International Classification of Diseases, Tenth Revision. However, it is very difficult to sustain any other diagnosis for the second child. In the third child, the illness has been evolving and the clinical picture changed from predominant mood symptoms to psychotic-like experiences at later stage. Therefore, at present a diagnosis of schizo-affective disorder is entertained. We could not find any possible organic etiology in any of the three cases with the best of our efforts.

With provision of pharmacological and psychosocial treatment in accordance to the available treatment guidelines,[ 15 ] remission was not achieved in two of the three children. Currently, the available evidence also suggests that the prognosis of childhood-onset schizophrenia is mainly poor as it disrupts the social and cognitive development and thus nearly two-third of children do not achieve remission.[ 16 ] On a positive note, we have been able to retain all the children in treatment.

Other issues faced by the families of three children and the treating team are briefly discussed below. In countries like India, where significant expenses are born by patients/family, associated stigma, limited social services, and the anti-psychotic related adverse effects raise the burden of care exponentially. In 2/3 index patients, the family bore the costs of special investigations, which was not possible in the second child and led to financial difficulties for the single mother of the first child. Adding on, the availability of rehabilitation services for children with major mental illnesses is scarce in various parts of our country. Furthermore, we successfully used ECT for management of acute disturbance in two of the three patients prior to the notification of Mental Health Care Act, 2017 that prohibits its use in minors. The case series also put forward a strong case for strengthening and sensitizing primary care physicians and pediatricians in identifying and treating cases of VEOP, since they are more likely to be the first points of contact with patients of the discussed age group. In view of the duration of untreated psychosis being a very eloquent prognostic factor for VEOP and the symptomatology of the same showing significant heterogeneity, armoring primary care physicians and pediatricians with the right skills to identify, treat, or refer patients with VEOP, especially in the prodromal period, might profoundly contribute in decreasing the morbidity and improving prognosis. Citing this lacuna which could be filled and used to our advantage, Stevens et al .[ 17 ] elaborated and discussed various questions which practitioners might find useful.

Childhood-onset schizophrenia is a rare occurrence. The current case series highlights differing clinical presentation of VEOS/VEOP in children and adolescents. Certain other issues pertinent to the management of VEOS/VEOP are also touched upon in this article. With the early recognition of childhood mental health illnesses, we need to build and strengthen ample child and adolescent mental health services in India.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Conflicts of interest.

There are no conflicts of interest.

Acknowledgement

The authors thank Dr. Sonam Arora, MD, DNB (Pathology), for providing assistance in laboratory investigations and article writing.

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

Schizophrenia case studies: putting theory into practice

This article considers how patients with schizophrenia should be managed when their condition or treatment changes.

DR P. MARAZZI/SCIENCE PHOTO LIBRARY

Treatments for schizophrenia are typically recommended by a mental health specialist; however, it is important that pharmacists recognise their role in the management and monitoring of this condition. In ‘ Schizophrenia: recognition and management ’, advice was provided that would help with identifying symptoms of the condition, and determining and monitoring treatment. In this article, hospital and community pharmacy-based case studies provide further context for the management of patients with schizophrenia who have concurrent conditions or factors that could impact their treatment.

Case study 1: A man who suddenly stops smoking

A man aged 35 years* has been admitted to a ward following a serious injury. He has been taking olanzapine 20mg at night for the past three years to treat his schizophrenia, without any problems, and does not take any other medicines. He smokes 25–30 cigarettes per day, but, because of his injury, he is unable to go outside and has opted to be started on nicotine replacement therapy (NRT) in the form of a patch.

When speaking to him about his medicines, he appears very drowsy and is barely able to speak. After checking his notes, it is found that the nurses are withholding his morphine because he appears over-sedated. The doctor asks the pharmacist if any of the patient’s prescribed therapies could be causing these symptoms.

What could be the cause?

Smoking is known to increase the metabolism of several antipsychotics, including olanzapine, haloperidol and clozapine. This increase is linked to a chemical found in cigarettes, but not nicotine itself. Tobacco smoke contains aromatic hydrocarbons that are inducers of CYP1A2, which are involved in the metabolism of several medicines [1] , [2] , [3] . Therefore, smoking cessation and starting NRT leads to a reduction in clearance of the patient’s olanzapine, leading to increased plasma levels of the antipsychotic olanzapine and potentially more adverse effects — sedation in this case.

Patients who want to stop, or who inadvertently stop, smoking while taking antipsychotics should be monitored for signs of increased adverse effects (e.g. extrapyramidal side effects, weight gain or confusion). Patients who take clozapine and who wish to stop smoking should be referred to their mental health team for review as clozapine levels can increase significantly when smoking is stopped [3] , [4] .

For this patient, olanzapine is reduced to 15mg at night; consequently, he seems much brighter and more responsive. After a period on the ward, he has successfully been treated for his injury and is ready to go home. The doctor has asked for him to be supplied with olanzapine 15mg for discharge along with his NRT.

What should be considered prior to discharge?

It is important to discuss with the patient why his dose was changed during his stay in hospital and to ask whether he intends to start smoking again or to continue with his NRT. Explain to him that if he wants to begin, or is at risk of, smoking again, his olanzapine levels may be impacted and he may be at risk of becoming unwell. It is necessary to warn him of the risk to his current therapy and to speak to his pharmacist or mental health team if he does decide to start smoking again. In addition, this should be used as an opportunity to reinforce the general risks of smoking to the patient and to encourage him to remain smoke-free.

It is also important to speak to the patient’s community team (e.g. doctors, nurses), who specialise in caring for patients with mental health disorders, about why the olanzapine dose was reduced during his stay, so that they can then monitor him in case he does begin smoking again.

Case 2: A woman with constipation

A woman aged 40 years* presents at the pharmacy. The pharmacist recognises her as she often comes in to collect medicine for her family. They are aware that she has a history of schizophrenia and that she was started on clozapine three months ago. She receives this from her mental health team on a weekly basis.

She has visited the pharmacy to discuss constipation that she is experiencing. She has noticed that since she was started on clozapine, her bowel movements have become less frequent. She is concerned as she is currently only able to go to the toilet about once per week. She explains that she feels uncomfortable and sick, and although she has been trying to change her diet to include more fibre, it does not seem to be helping. The patient asks for advice on a suitable laxative.

What needs to be considered?

Constipation is a very common side effect of clozapine . However, it has the potential to become serious and, in rare cases, even fatal [5] , [6] , [7] , [8] . While minor constipation can be managed using over-the-counter medicines (e.g. stimulant laxatives, such as senna, are normally recommended first-line with stool softeners, such as docusate, or osmotic laxatives, such as lactulose, as an alternative choice), severe constipation should be checked by a doctor to ensure there is no serious bowel obstruction as this can lead to paralytic ileus, which can be fatal [9] . Symptoms indicative of severe constipation include: no improvement or bowel movement following laxative use, fever, stomach pain, vomiting, loss of appetite and/or diarrhoea, which can be a sign of faecal impaction overflow.

As the patient has been experiencing this for some time and is only opening her bowels once per week, as well as having other symptoms (i.e. feeling uncomfortable and sick), she should be advised to see her GP as soon as possible.

The patient returns to the pharmacy again a few weeks later to collect a prescription for a member of their family and thanks the pharmacist for their advice. The patient was prescribed a laxative that has led to resolution of symptoms and she explains that she is feeling much better. Although she has a repeat prescription for lactulose 15ml twice per day, she says she is not sure whether she needs to continue to take it as she feels better.

What advice should be provided?

As she has already had an episode of constipation, despite dietary changes, it would be best for the patient to continue with the lactulose at the same dose (i.e. 15ml twice daily), to prevent the problem occurring again. Explain to the patient that as constipation is a common side effect of clozapine, it is reasonable for her to take laxatives before she gets constipation to prevent complications.

Pharmacists should encourage any patient who has previously had constipation to continue taking prescribed laxatives and explain why this is important. Pharmacists should also continue to ask patients about their bowel habits to help pick up any constipation that may be returning. Where pharmacists identify patients who have had problems with constipation prior to starting clozapine, they can recommend the use of a prophylactic laxative such as lactulose.

Case 3: A mother is concerned for her son who is talking to someone who is not there

A woman has been visiting the pharmacy for the past 3 months to collect a prescription for her son, aged 17 years*. In the past, the patient has collected his own medicine. Today the patient has presented with his mother; he looks dishevelled, preoccupied and does not speak to anyone in the pharmacy.

His mother beckons you to the side and expresses her concern for her son, explaining that she often hears him talking to someone who is not there. She adds that he is spending a lot of time in his room by himself and has accused her of tampering with his things. She is not sure what she should do and asks for advice.

What action can the pharmacist take?

It is important to reassure the mother that there is help available to review her son and identify if there are any problems that he is experiencing, but explain it is difficult to say at this point what he may be experiencing. Schizophrenia is a psychotic illness which has several symptoms that are classified as positive (e.g. hallucinations and delusions), negative (e.g. social withdrawal, self-neglect) and cognitive (e.g. poor memory and attention).

Many patients who go on to be diagnosed with schizophrenia will experience a prodromal period before schizophrenia is diagnosed. This may be a period where negative symptoms dominate and patients may become isolated and withdrawn. These symptoms can be confused with depression, particularly in younger people, though depression and anxiety disorders themselves may be prominent and treatment for these may also be needed. In this case, the patient’s mother is describing potential psychotic symptoms and it would be best for her son to be assessed. She should be encouraged to take her son to the GP for an assessment; however, if she is unable to do so, she can talk to the GP herself. It is usually the role of the doctor to refer patients for an assessment and to ensure that any other medical problems are assessed. 

Three months later, the patient comes into the pharmacy and seems to be much more like his usual self, having been started on an antipsychotic. He collects his prescription for risperidone and mentions that he is very worried about his weight, which has increased since he started taking the newly prescribed tablets. Although he does not keep track of his weight, he has noticed a physical change and that some of his clothes no longer fit him.

What advice can the pharmacist provide?

Weight gain is common with many antipsychotics [10] . Risperidone is usually associated with a moderate chance of weight gain, which can occur early on in treatment [6] , [11] , [12] . As such, the National Institute for Health and Care Excellence recommends weekly monitoring of weight initially [13] . As well as weight gain, risperidone can be associated with an increased risk of diabetes and dyslipidaemia, which must also be monitored [6] , [11] , [12] . For example, the lipid profile and glucose should be assessed at 12 weeks, 6 months and then annually [12] .

The pharmacist should encourage the patient to attend any appointments for monitoring, which may be provided by his GP or mental health team, and to speak to his mental health team about his weight gain. If he agrees, the pharmacist could inform the patient’s mental health team of his weight gain and concerns on his behalf. It is important to tackle weight gain early on in treatment, as weight loss can be difficult to achieve, even if the medicine is changed.

The pharmacist should provide the patient with advice on healthy eating (e.g. eating a balanced diet with at least five fruit and vegetables per day) and exercising regularly (e.g. doing at least 150 minutes of moderate-intensity activity or 75 minutes of vigorous-intensity activity per week), and direct him to locally available services. The pharmacist can record the adverse effect on the patient’s medical record, which will help flag this in the future and thus help other pharmacists to intervene should he be prescribed risperidone again.

*All case studies are fictional.

Useful resources

• Mind — Schizophrenia
• Rethink Mental Illness — Schizophrenia
• Mental Health Foundation — Schizophrenia
• Royal College of Psychiatrists — Schizophrenia
• NICE guidance [CG178] — Psychosis and schizophrenia in adults: prevention and management
• NICE guidance [CG155] — Psychosis and schizophrenia in children and young people: recognition and management
• British Association for Psychopharmacology — Evidence-based guidelines for the pharmacological treatment of schizophrenia: updated recommendations from the British Association for Psychopharmacology

About the author

Nicola Greenhalgh is lead pharmacist, Mental Health Services, North East London NHS Foundation Trust

[1] Chiu CC, Lu ML, Huang MC & Chen KP. Heavy smoking, reduced olanzapine levels, and treatment effects: a case report. Ther Drug Monit 2004;26(5):579–581. doi: 10.1097/00007691-200410000-00018

[2] de Leon J. Psychopharmacology: atypical antipsychotic dosing: the effect of smoking and caffeine. Psychiatr Serv 2004;55(5):491–493. doi: 10.1176/appi.ps.55.5.491

[3] Mayerova M, Ustohal L, Jarkovsky J et al . Influence of dose, gender, and cigarette smoking on clozapine plasma concentrations. Neuropsychiatr Dis Treat 2018;14:1535–1543. doi: 10.2147/NDT.S163839

[4] Ashir M & Petterson L. Smoking bans and clozapine levels. Adv Psychiatr Treat 2008;14(5):398–399. doi: 10.1192/apt.14.5.398b

[5] Young CR, Bowers MB & Mazure CM. Management of the adverse effects of clozapine. Schizophr Bull 1998;24(3):381–390. doi: 10.1093/oxfordjournals.schbul.a033333

[6] Taylor D, Barnes TRE & Young AH. The Maudsley Prescribing Guidelines in Psychiatry . 13th edn. London: Wiley Blackwell; 2018

[7] Oke V, Schmidt F, Bhattarai B et al . Unrecognized clozapine-related constipation leading to fatal intra-abdominal sepsis — a case report. Int Med Case Rep J 2015;8:189–192. doi: 10.2147/IMCRJ.S86716

[8] Hibbard KR, Propst A, Frank DE & Wyse J. Fatalities associated with clozapine-related constipation and bowel obstruction: a literature review and two case reports. Psychosomatics 2009;50(4):416–419. doi: 10.1176/appi.psy.50.4.416

[9] Medicines and Healthcare products Regulatory Agency. Clozapine: reminder of potentially fatal risk of intestinal obstruction, faecal impaction, and paralytic ileus. 2020. Available from: https://www.gov.uk/drug-safety-update/clozapine-reminder-of-potentially-fatal-risk-of-intestinal-obstruction-faecal-impaction-and-paralytic-ileus (accessed April 2020)

[10] Leucht S, Cipriani A, Spineli L et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 2013;382(9896):951–962. doi: 10.1016/S0140-6736(13)60733-3

[11] Bazire S. Psychotropic Drug Directory . Norwich: Lloyd-Reinhold Communications LLP; 2018

[12] Cooper SJ & Reynolds GP. BAP guidelines on the management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and antipsychotic drug treatment. J Psychopharmacol 2016;30(8):717–748. doi: 10.1177/0269881116645254

[13] National Institute for Health and Care Excellence. Psychosis and schizophrenia in adults: prevention and management. Clinical guideline [CG178]. 2014. Available from: https://www.nice.org.uk/guidance/cg178 (accessed April 2020)

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Case Study: Schizophrenia and Work: Martin’s Story

Martin had been out of work for several years following a prolonged psychotic episode which began when he was studying at university. He desperately wanted to get into work but found that employers treated his prolonged absence “on the sick” with suspicion. He thought that if he could do a period of work experience that would show prospective employers that he was capable of working again but he was afraid that if he did it might affect his benefits.

So Martin made an appointment to see the Disability Employment Advisor at the Jobcentre to discuss his plans. She was understanding and helpful and explained that a work placement would not affect his benefits as long as it was done as part of the Jobcentre’s own scheme. She also told him that the scheme would pay his travel-to work expenses while he was on the placement.

Job-searching

Next Martin researched local employers using the internet and the local press, looking for companies that might have vacancies in the sort of clerical and administrative work he thought he could do. Then he called the companies by ‘phone and speaking to the person on the switchboard checked that he had the correct postal address for them and asked the name of the person in charge of recruiting. It is vital to be able to write to a named person rather than just the Human Resources Manager.

Martin had already spent a lot of time on his CV so now he compiled a covering letter to go with it. It took him about a month to work up his CV and covering letter using books that he got from the local library. He also managed to get advice from a local back-to-work scheme recommended by the Disability Employment Advisor at the Jobcentre. Martin knew that it was essential that his letter and CV had the maximum impact.

Martin sent his CV and letter off to six employers and then waited about a week before calling them up on the ‘phone. He asked to speak to the person he had written to but if the person on the switchboard asked the reason for his call he simply said that he was calling to follow up a letter he had written.

After approaching about 20 employers in this way he finally found one who said there could be an opening for work experience in a couple of months time. So over the next three months Martin kept in touch with the company by ‘phone once a month just to let them know that he was still keen on coming to work for them.

The interview

Finally the company asked him in for an interview. Before going to the interview Martin prepared really well in advance by researching the company well and trying to anticipate the sorts of questions he would be asked. He also went to the local library and took out some books on interview techniques and managed to get on a one day course on interview skills that the Jobcentre had told him about. This included a mock interview which he found particularly useful.

The day of the interview arrived and Martin was very nervous but he was up early and washed and dressed. To be sure of being on time he left an hour early and checked out the location of the office. Then he went to Starbucks for a coffee while he waited. This gave him an opportunity to flick through his notes and prepare on some of the answers he had been working on. He made sure that he was punctual and well groomed and did his best to present himself well at the interview.

Despite being really well prepared walking through the front door of the office was one of the hardest things that he had done for years. But the receptionist was polite and could not have been more helpful. She made him feel welcome and even offered him a coffee (which he declined).

The Human Resources Manager who interviewed Martin was very professional but quickly put him at his ease. He asked questions about his education at school, his hobbies and pastimes and his qualifications and then came the bit that Martin had been dreading when the HR Manager asked him why he had dropped out of college. Martin explained that he had had a breakdown caused by too much stress while he was at college. He went on to explain that although it was a bad breakdown it was behind him now and that with the help of his family and friends and his doctor he had been able to make a really strong recovery. He also explained that in some ways the experience had made him a stronger person and that he had matured as a result of it.

As the end of the interview approached Martin was sure that he had flunked it but the interviewer told him that he had been successful and asked him to start on Monday. Martin was delighted to be offered a period of three months unpaid work experience during which he would work for two days a week at their local office doing clerical and administrative work.

Martin was walking on air when he left the office. All his hard work had been worth it.

The next day Martin called the Disability Employment Advisor at the local Jobcentre to tell them about the offer and see how his benefits would be affected. She confirmed that his benefits wouldn’t be affected as long as he only worked for 16 hours a week.

The placement

For the next three months Martin worked hard at his placement. He made sure that he got all the basics right: being punctual and well groomed every day. At work he was helpful and got on well with the other workers. Although he was very shy at first he soon learned the importance of making small talk with his colleagues and building good working relationships.

As the end of his placement approached Martin wondered if he would be offered a permanent position. He asked the HR Manager about this but sadly he was told that there were no permanent vacancies at that time so when the end of his placement came Martin had mixed feelings. On the one hand he was disappointed that the work experience had not turned into a permanent job but on the other hand he had had three months experience in the workplace and had something to put on his CV to demonstrate to other employers that he could work. And most importantly he had that all important reference from a well respected local employer.

But that isn’t quite the end of the story. Martin continued searching for a job without success for another six months but continued to keep in touch with the HR Manager he had worked for during his work experience. One day he saw in the local press that they were advertising for a clerical assistant so he called them and explained that he was still jobsearching and would be available for this position. The HR Manager was very pleased to hear from him and said that he would call him back. The next day Martin got a call asking him to go in for an interview straight away and was offered the job.

Martin called the Jobcentre Plus helpline and found out what benefits he would be entitled to while he was working and was pleased to find out that he would be better off in work.

Martin has now been employed in his new job for two years and is delighted to be living an independent lifestyle free of the benefits culture he was in before. It has had its difficulties though. For instance Martin found that his illness had left him emotionally very sensitive and that he found it difficult to cope if his work was criticised. But he knew that this was something he had to learn to live with and gradually he managed to learn new social skills that helped him to cope better and at the same time helped him in other areas of his life.

Martin has enjoyed the structure that the new job has brought to his life. He enjoys the work and the social contact that the job entails. He has made new friends and above all his self-esteem has grown vastly. Now when people ask him what he does for a living he no longer has to say that he is unemployed.

Some Key Points from Martin’s Story:

• Research the local job market really well
• Before writing to a firm call to check the postal address.
• Find out the name of the person in charge of recruitment. Writing to a named person makes sure your letter gets read.
• You can’t spend enough time preparing your CV and cover letter. Get as much help as you can from books, the library etc.
• When making follow up calls avoid Mondays and Fridays as these are busy days for people in business. Similarly don’t call too early in the morning or after 3.30 pm and don’t call around lunchtime.
• When making follow up calls be prepared for few false starts but use these to develop your technique. Treat the first half a dozen calls as practice calls.
• Don’t pester firms with too frequent follow up calls. Once every three weeks is about right.
• Be prepared for disappointment and don’t feel let down by it.
• Before going for an interview research the firm really well. Google and Google News and the local press are useful sources.
• It is perfectly normal to be nervous at an interview. Try to minimise the nerves by making sure you have planned and prepared well and getting a good night’s sleep beforehand.
• At the interview you may be asked about your illness. Be honest but there is no need to disclose your diagnosis at this stage unless you are asked directly: a broad brush explanation such as “a breakdown” is sufficient.

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Case Study Illustrates How Schizophrenia Can Often Be Overdiagnosed

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Study shows how schizophrenia can often be over diagnosed. Learn how. Click to Tweet

Study author Russell Margolis, director of the Johns Hopkins Schizophrenia Center, answers questions on misdiagnosis of the condition and reiterates the importance of thorough examination.

It’s not uncommon for an adolescent or young adult who reports hearing voices or seeing things to be diagnosed with schizophrenia, but using these reports alone can contribute to the disease being overdiagnosed, says  Russell Margolis , clinical director of the Johns Hopkins Schizophrenia Center. 

Many clinicians consider hallucinations as the sine qua non, or essential condition, of schizophrenia, he says. But even a true hallucination might be part of any number of disorders — or even within the range of normal. To diagnose a patient properly, he says, “There’s no substitute for taking time with patients and others who know them well. Trying to [diagnose] this in a compressed, shortcut kind of way leads to error.”

A case study he shared recently in the  Journal of Psychiatric Practice  illustrates the problem. Margolis, along with colleagues Krista Baker, schizophrenia supervisor at Johns Hopkins Bayview Medical Center, visiting resident Bianca Camerini, and Brazilian psychiatrist Ary Gadelha, described a 16-year-old girl who was referred to the Early Psychosis Intervention Clinic at Johns Hopkins Bayview for a second opinion concerning the diagnosis and treatment of suspected schizophrenia.

The patient made friends easily but had some academic difficulties. Returning to school in eighth grade after a period of home schooling, she was bullied, sexually groped and received texted death threats. She then began to complain of visions of a boy who harassed her, as well as three tall demons. The visions waxed and waned in relation to stress at school. The Johns Hopkins consultants determined that this girl did not have schizophrenia (or any other psychotic disorder), but that she had anxiety. They recommended psychotherapy and viewing herself as a healthy, competent person, instead of a sick one. A year later, the girl reported doing well: She was off medications and no longer complained of these visions.

Margolis answers  Hopkins Brain Wise ’s questions.

Q: How are anxiety disorders mistaken for schizophrenia?

A:  Patients often say they have hallucinations, but that doesn’t always mean they’re experiencing a true hallucination. What they may mean is that they have very vivid, distressing thoughts — in part because hallucinations have become a common way of talking about distress, and partly because they may have no other vocabulary with which to describe their experience. 

Then, even if it  is  a true hallucination, there are features of the way psychiatry has come to be practiced that cause difficulties. Electronic medical records are often designed with questionnaires that have yes or no answers. Sometimes, whether the patient has hallucinations is murky, or  possible —  not yes or no. Also, one can’t make a diagnosis based just on a hallucination; the diagnosis of disorders like schizophrenia is based on a constellation of symptoms. 

Q: How often are patients in this age range misdiagnosed?

A:  There’s no true way to know the numbers. Among a very select group of people in our consultation clinic where questions have been raised, about half who were referred to us and said to have schizophrenia or a related disorder did not. That is not generalizable.

Q:   Why does that happen?

A:  There is a lack of attention to the context of symptoms and other details, and there’s also a tendency to take patients literally. If a patient complains about x, there’s sometimes a pressure to directly address x. In fact, that’s not appropriate medicine. It is very important to pay attention to a patient’s stated concerns, but to place these concerns in the bigger picture. Clinicians can go too far in accepting at face value something that needs more exploration. 

Q: What lessons do you hope to impart by publishing this case?

A:  I want it to be understood that the diagnosis of schizophrenia has to be made with care. Clinicians need to take the necessary time and obtain the necessary information so that they’re not led astray. Eventually, we would like to have more objective measures for defining our disorders so that we do not need to rely totally on a clinical evaluation. 

Learn more about Russell Margolis’ research regarding the challenges of diagnosing schizophrenia .

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Case Reports in Schizophrenia and Psychotic Disorders: 2023

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• Published: 08 April 2022

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

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Schizophrenia Working Group of the Psychiatric Genomics Consortium

Nature volume  604 ,  pages 502–508 ( 2022 ) Cite this article

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• Diseases of the nervous system
• Genetics of the nervous system
• Genome-wide association studies
• Schizophrenia

Schizophrenia has a heritability of 60–80% 1 , much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4 , and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.

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GAGE-seq concurrently profiles multiscale 3D genome organization and gene expression in single cells

Data availability.

Summary statistics for the ‘extended’, ‘core’, ancestry-specific and sex-stratified analyses are available at https://www.med.unc.edu/pgc/download-results/scz/ . Genotype data are available for a subset of cohorts, including dbGAP accession numbers and/or restrictions, as described in the ‘Case–control sample descriptions’ section of the Supplementary Information.

Code availability

Core analysis code for RICOPILI can be found at https://sites.google.com/a/broadinstitute.org/ricopili/ . This wraps PLINK ( https://www.cog-genomics.org/plink2/ ), EIGENSOFT ( https://www.hsph.harvard.edu/alkes-price/software/ ), Eagle2 ( https://alkesgroup.broadinstitute.org/Eagle/ ), Minimac3 ( https://genome.sph.umich.edu/wiki/Minimac3 ), SHAPEIT3 ( https://mathgen.stats.ox.ac.uk/genetics_software/shapeit/shapeit.html ), METAL ( https://genome.sph.umich.edu/wiki/METAL_Documentation ) and LDSR ( https://github.com/bulik/ldsc ). For downstream analyses, FINEMAP can be found at http://christianbenner.com/ , and our utility for meta-analysing cohort-specific LD matrices can be found at https://github.com/Pintaius/LDmergeFM . MAGMA can be found at https://ctg.cncr.nl/software/magma and the GO gene sets and automated curation pipeline are provided in https://github.com/janetcharwood/pgc3-scz_wg-genesets . SMR is available at https://cnsgenomics.com/software/smr/ and SbayesS at https://cnsgenomics.com/software/gctb/ .

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Acknowledgements

The National Institute of Mental Health (USA) provides core funding for the PGC under award no. U01MH109514. The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The work of the contributing groups was supported by numerous grants from governmental and charitable bodies as well as philanthropic donation (details in  Supplementary Note ). We acknowledge a substantial contribution from P. Sklar (deceased) as one of the PGC principal investigators, and E. Scolnick, whose support for this study was vital. We acknowledge the Wellcome Trust Case Control Consortium for the provision of control genotype information. Membership of the Psychosis Endophenotypes International Consortium, the SynGO consortium, the PsychENCODE Consortium, the eQTLGen consortium, the BIOS Consortium and the Indonesia Consortium are provided in the author list. We are grateful to C. Hopkins for illustrations. The work at Cardiff University was additionally supported by Medical Research Council Centre grant no. MR/L010305/1 and program grant no. G0800509. S. Xu also gratefully acknowledges the support of the National Natural Science Foundation of China (NSFC) grants (31525014, 91731303, 31771388, 31961130380 and 32041008), the UK Royal Society-Newton Advanced Fellowship (NAF\R1\191094), the Key Research Program of Frontier Sciences (QYZDJ-SSW-SYS009) and the Strategic Priority Research Program (XDB38000000) of the Chinese Academy of Sciences, and the Shanghai Municipal Science and Technology Major Project (2017SHZDZX01). O. A. Andreassen was supported by the Research Council of Norway (283798, 262656, 248980, 273291, 248828, 248778, 223273); KG Jebsen Stiftelsen, South-East Norway Health Authority, EU H2020 no. 847776. B. Melegh was supported in part by the National Scientific Research Program (NKFIH) K 138669. S. V. Faraone is supported by the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602805, the European Union’s Horizon 2020 research and innovation programme under grant agreements 667302 and 728018 and NIMH grants 5R01MH101519 and U01 MH109536-01. S. I. Belangero was supported by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo), grant numbers: 2010/08968-6; 2014/07280-1 2011/50740-5 (including R. A. Bressan). The Singapore team (J. Lee, J. Liu, K. Sim, S. A. Chong and M. Subramanian) acknowledges the National Medical Research Council Translational and Clinical Research Flagship Programme (grant no.: NMRC/TCR/003/2008). M. Macek was supported by LM2018132, CZ.02.1.01/0.0/0.0/18_046/0015515 and IP6003 –VZFNM00064203. C. Arango has been funded by the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024), co-financed by ERDF Funds from the European Commission, ‘A way of making Europe’, CIBERSAM, Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds, European Union Seventh Framework Program and European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement no 115916, project PRISM; and grant agreement no. 777394, project AIMS-2-TRIALS), Fundación Familia Alonso and Fundación Alicia Koplowitz. E. Bramon acknowledges support from the National Institute of Health Research UK (grant NIHR200756); Mental Health Research UK John Grace QC Scholarship 2018; an ESRC collaborative award 2020; BMA Margaret Temple Fellowship 2016; Medical Research Council New Investigator Award (G0901310); MRC Centenary Award (G1100583); MRC project grant G1100583; National Institute of Health Research UK post-doctoral fellowship (PDA/02/06/016); NARSAD Young Investigator awards 2005 and 2008; Wellcome Trust Research Training Fellowship; Wellcome Trust Case Control Consortium awards (085475/B/08/Z, 085475/Z/08/Z); European Commission Horizon 2020 (747429); NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and King’s College London; and NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London (UCLH BRC - Mental Health Theme). D. Molto is funded by the European Regional Development Fund (ERDF)–Valencian Community 2014–2020, Spain. E. G. Atkinson was supported by the NIMH K01MH121659.

Author information

These authors contributed equally: Vassily Trubetskoy, Antonio F. Pardiñas

These authors jointly supervised this work: Stephan Ripke, James T. R. Walters, Michael C. O’Donovan

Deceased: Robert W. McCarley

Authors and Affiliations

Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany

Vassily Trubetskoy, Georgia Panagiotaropoulou, Swapnil Awasthi, Alice Braun, Julia Kraft, Nora Skarabis, Henrik Walter & Stephan Ripke

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK

Antonio F. Pardiñas, Charlotte A. Dennison, Lynsey S. Hall, Janet C. Harwood, Alexander L. Richards, Sophie E. Legge, Amy Lynham, Nigel M. Williams, Nicholas J. Bray, Valentina Escott-Price, George Kirov, Peter A. Holmans, Andrew J. Pocklington, Michael J. Owen, James T. R. Walters & Michael C. O’Donovan

Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia

Ting Qi, Julia Sidorenko, Yang Wu, Jian Zeng, Jacob Gratten, Peter M. Visscher, Jian Yang & Naomi R. Wray

School of Life Sciences, Westlake University, Hangzhou, China

Ting Qi & Jian Yang

Department of Psychiatry and the Behavioral Sciences, SUNY Downstate Medical Center, New York, NY, USA

Tim B. Bigdeli

Institute for Genomic Health, SUNY Downstate Medical Center, New York, NY, USA

Department of Psychiatry, Veterans Affairs New York Harbor Healthcare System, New York, NY, USA

Tim B. Bigdeli & Ayman H. Fanous

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

Julien Bryois, Sarah E. Bergen, Anna K. Kähler, Patrik K. E. Magnusson, Christina M. Hultman & Patrick F. Sullivan

Biogen, Cambridge, MA, USA

Chia-Yen Chen

Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA

Chia-Yen Chen, Elizabeth G. Atkinson, Jacqueline I. Goldstein, Daniel P. Howrigan, Alicia R. Martin, Mark J. Daly, Hailiang Huang, Benjamin M. Neale & Stephan Ripke

Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA

Chia-Yen Chen & Tian Ge

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA

Max Lam, Tian Ge, Elizabeth G. Atkinson, Richard A. Belliveau, Kimberley D. Chambert, Giulio Genovese, Phil H. Lee, Alicia R. Martin, Olli Pietiläinen, Steven A. McCarroll, Jennifer L. Moran, Jordan W. Smoller, Tyler C. Brown, Guoping Feng, Steven E. Hyman, Morgan Sheng, Steven E. Hyman, Hailiang Huang & Benjamin M. Neale

Research Division, Institute of Mental Health, Singapore, Republic of Singapore

Max Lam, Siow Ann Chong & Mythily Subramaniam

Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA

Max Lam, Todd Lencz & Anil K. Malhotra

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

Kyoko Watanabe

NORMENT Centre, Division of Mental Health and Addiction, University of Oslo, Oslo, Norway

Oleksandr Frei, Ingrid Agartz, Lavinia Athanasiu, Ingrid Melle & Ole A. Andreassen

Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway

Oleksandr Frei, Lavinia Athanasiu, Ingrid Melle, Nils Eiel Steen & Ole A. Andreassen

Center for Bioinformatics, Department of Informatics, University of Oslo, Oslo, Norway

Oleksandr Frei

Department of Psychiatry, Harvard Medical School, Boston, MA, USA

Tian Ge, Lynn E. DeLisi, Raquelle I. Mesholam-Gately & Larry J. Seidman

Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Faculty of Science, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, The Netherlands

Frank Koopmans

deCODE Genetics, Amgen, Reykjavik, Iceland

Sigurdur Magnusson, Hreinn Stefánsson & Kari Stefansson

The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark

Jakob Grove, Esben Agerbo, Thomas D. Als, Jonas Bybjerg-Grauholm, Ditte Demontis, David M. Hougaard, Ole Mors, Preben B. Mortensen, Merete Nordentoft & Anders D. Børglum

Department of Biomedicine and Centre for Integrative Sequencing (iSEQ), Aarhus University, Aarhus, Denmark

Jakob Grove, Thomas D. Als, Ditte Demontis, Manuel Mattheisen & Anders D. Børglum

Center for Genomics and Personalized Medicine, Aarhus, Denmark

Jakob Grove, Thomas D. Als, Ditte Demontis & Anders D. Børglum

Department of Psychiatry, Semel Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

Minsoo Kim & Michael J. Gandal

Affiliated Hospital of Qingdao University and Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University, Qingdao, China

Zhiqiang Li, Yongyong Shi & Yongyong Shi

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University, Shanghai, China

Zhiqiang Li, Wei Zhou, Shengying Qin, Yongyong Shi & Yongyong Shi

Department of Psychiatry, Pamela Sklar Division of Psychiatric Genomics, Friedman Brain Institute, Department of Genetics and Genomic Science and Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

Georgios Voloudakis, Wen Zhang & Panos Roussos

Department of Genetics and Genomic Sciences and Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK

Mark Adams & Andrew McIntosh

Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway

Ingrid Agartz

Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden

Ingrid Agartz, Erik Söderman & Erik G. Jönsson

National Centre for Register-based Research, Aarhus University, Aarhus, Denmark

Esben Agerbo, John J. McGrath & Preben B. Mortensen

Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, London, UK

Mariam Al Eissa, Nicholas J. Bass, Alessia Fiorentino, Niamh Louise O’Brien, Jonathan Pimm, Sally Isabel Sharp & Andrew McQuillin

Comedicum Lindwurmhof, Munich, Germany

Margot Albus

Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA, USA

Madeline Alexander

University Medical Center Groningen, University Center for Psychiatry, Rob Giel Research Center, University of Groningen, Groningen, The Netherlands

Behrooz Z. Alizadeh & Richard Bruggeman

Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Behrooz Z. Alizadeh

Department of Psychiatry, Dokuz Eylül University School of Medicine, Izmir, Turkey

Köksal Alptekin

Department of Neuroscience, Dokuz Eylül University Graduate School of Health Sciences, Izmir, Turkey

Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA

Farooq Amin

Department of Psychiatry, University of Münster, Münster, Germany

Volker Arolt, Rebecca Lencer, Matthias Rothermundt & Bernhard T. Baune

Servizo de Psiquiatría, Complexo Hospitalario Universitario de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain

Manuel Arrojo

Institute of Medical Psychology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

Maria Helena Azevedo

Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA

Silviu A. Bacanu, Bradley T. Webb, Brandon K. Wormley, Brien P. Riley & Kenneth S. Kendler

Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany

Martin Begemann, Marina Mitjans, Agnes A. Steixner-Kumar & Hannelore Ehrenreich

Department of Medical Genetics, Medical School, University of Pécs, Pécs, Hungary

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UniSA Allied Health and Human Performance, University of South Australia, Adelaide, South Australia, Australia

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Giuseppe Blasi, Antonio Rampino, Silvia Torretta & Alessandro Bertolino

Área de Psiquiatría-Universidad de Oviedo, Hospital Universitario Central de Asturias (HUCA), Asturias, Spain

Julio Bobes

Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Asturias, Spain

Centro de Investigación Biomédica en Red de Salud Mental, Oviedo, Asturias, Spain

Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Roma and San Raffaele University, Rome, Italy

Stefano Bonassi

Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil

Rodrigo Affonseca Bressan, Ary Gadelha & Cristiano Noto

Laboratory of Integrative Neuroscience, Universidade Federal de São Paulo, São Paulo, Brazil

Rodrigo Affonseca Bressan, Ary Gadelha, Cristiano Noto, Vanessa Kiyomi Ota, Marcos Leite Santoro & Sintia Iole Belangero

Department of Psychiatry and Behavioural Health, Stony Brook University, Stony Brook, NY, USA

Evelyn J. Bromet

Department of Clinical and Developmental Neuropsychology, University of Groningen, Groningen, The Netherlands

Richard Bruggeman

Health Science Center, University of Tennessee, Memphis, TN, USA

Peter F. Buckley

Department of Psychology, Harvard University, Cambridge, MA, USA

Randy L. Buckner

Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark

Jonas Bybjerg-Grauholm & David M. Hougaard

University Medical Center Utrecht, Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, Utrecht, The Netherlands

Wiepke Cahn & René S. Kahn

Altrecht, General Menthal Health Care, Utrecht, The Netherlands

Wiepke Cahn

School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia

Murray J. Cairns, Rodney J. Scott & Paul A. Tooney

Hunter Medical Research Institute, Newcastle, New South Wales, Australia

Murray J. Cairns, Ulrich Schall, Rodney J. Scott & Paul A. Tooney

Centre for Brain and Mental Health Research, University of Newcastle, Newcastle, New South Wales, Australia

Murray J. Cairns & Paul A. Tooney

Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA

Monica E. Calkins, Raquel E. Gur, Ruben C. Gur & Bruce I. Turetsky

School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia

Vaughan J. Carr

Department of Psychiatry, Monash University, Melbourne, Victoria, Australia

Neuroscience Research Australia, Sydney, New South Wales, Australia

Department of Psychiatry, University of Melbourne, Parkville, Victoria, Australia

David Castle & Carol Harvey

St Vincent’s Hospital, Melbourne, Victoria, Australia

David Castle

Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia

Stanley V. Catts

School of Medicine, University of Queensland, Herston, Queensland, Australia

Institute of Psychology, Chinese Academy of Science, Beijing, China

Raymond C. K. Chan

Department of Psychology, University of Chinese Academy of Sciences, Beijing, China

INSERM U1266, Institute of Psychiatry and Neuroscience of Paris, Université de Paris, GHU Paris Psychiatrie & Neurosciences, Paris, France

Boris Chaumette, Oussama Kebir & Marie-Odile Krebs

Department of Psychiatry, McGill University, Montreal, Québec, Canada

Boris Chaumette

Department of Computer Science, University of North Carolina, Chapel Hill, NC, USA

Castle Peak Hospital, Hong Kong, China

Eric F. C. Cheung

Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Republic of Singapore

Siow Ann Chong & Mythily Subramaniam

Faculté de Médecine Sorbonne Université, Groupe de Recherche Clinique no. 15 - Troubles Psychiatriques et Développement (PSYDEV), Department of Child and Adolescent Psychiatry, Hôpital Universitaire de la Pitié-Salpêtrière, Paris, France

David Cohen, Angèle Consoli, Marianna Giannitelli & Claudine Laurent-Levinson

Centre de Référence des Maladies Rares à Expression Psychiatrique, Department of Child and Adolescent Psychiatry, AP-HP Sorbonne Université, Hôpital Universitaire de la Pitié-Salpêtrière, Paris, France

Institut des Systèmes Intelligents et de Robotique (ISIR), CNRS UMR7222, Faculté des Sciences et Ingénierie, Sorbonne Université, Paris, France

David Cohen

Department of Psychiatry, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil

Quirino Cordeiro

Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain

Javier Costas

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

Charles Curtis, Diego Quattrone, Gerome Breen, David A. Collier, Marta Di Forti & Evangelos Vassos

National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, London, UK

Charles Curtis, Valeria Mondelli, Diego Quattrone, Therese van Amelsvoort, Marta Di Forti, Robin M. Murray, Evangelos Vassos & Therese van Amelsvoort

University of Nicosia Medical School, Nicosia, Cyprus

Michael Davidson

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA

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Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands

Lieuwe de Haan & Lieuwe de Haan

Arkin, Institute for Mental Health, Amsterdam, The Netherlands

Institute of Human Genetics, University of Bonn, Bonn, Germany

Franziska Degenhardt, Andreas Forstner & Markus M. Nöthen

Cambridge Health Alliance, Cambridge, MA, USA

Lynn E. DeLisi

Sheppard Pratt Health System, Baltimore, MD, USA

Faith Dickerson

First Department of Psychiatry, Medical School, National and Kapodistrian University of Athens, Eginition Hospital, Athens, Greece

Dimitris Dikeos & George N. Papadimitriou

Department of Psychiatry and Neurobehavioural Sciences, University College Cork, Cork, Ireland

Timothy Dinan

APC Microbiome Ireland, University College Cork, Cork, Ireland

NORMENT Centre, Department of Clinical Science, University of Bergen, Bergen, Norway

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Department of Medical Genetics, Oslo University Hospital, Oslo, Norway

Center for Psychiatric Genetics, NorthShore University HealthSystem, Evanston, IL, USA

Jubao Duan, Pablo V. Gejman & Alan R. Sanders

Department of Psychiatry and Behavioral Neurosciences, The University of Chicago, Chicago, IL, USA

Department of Mental Health, ASL Rome 1, Rome, Italy

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Department of Health Sciences, University of Leicester, Leicester, UK

Frank Dudbridge

Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

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Folkhälsan Research Center, Helsinki, Finland

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Centro de Investigación Biomédica en Red en Salud Mental (CIBERSAM), Madrid, Spain

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Departments of Psychiatry and Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA

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Centre for Human Genetics, University of Marburg, Marburg, Germany

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Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

Josef Frank, Fabian Streit, Stephanie H. Witt & Marcella Rietschel

Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

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Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA

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Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA

Menachem Fromer & Eli A. Stahl

Barnet, Enfield and Haringey Mental Health NHS Trust, St Ann’s Hospital, London, UK

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Departments of Psychiatry and Human Genetics, University of Chicago, Chicago, IL, USA

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Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria

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Department of Genetics, University of North Carolina, Chapel Hill, NC, USA

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Departments of Psychiatry and Human and Molecular Genetics, INSERM, Institut de Myologie, Hôpital de la Pitiè-Salpêtrière, Paris, France

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Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, Madrid, Spain

Javier González Peñas, Carmen Moreno, Mara Parellada & Celso Arango

BIOARABA Health Research Institute, OSI Araba, University Hospital, University of the Basque Country, Vitoria, Spain

Ana González-Pinto

Neuroscience Therapeutic Area, Janssen Research and Development, Titusville, NJ, USA

Srihari Gopal, Adam Savitz & Qingqin S. Li

Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia

Jacob Gratten

Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

Michael F. Green, Keith H. Nuechterlein & Catherine A. Sugar

VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA

Michael F. Green

Department of Psychiatry, University of California San Diego, La Jolla, CA, USA

Tiffany A. Greenwood, Gregory A. Light, Neal R. Swerdlow & David Braff

INSERM, Rouen, France

Olivier Guillin & Dominique Campion

Centre Hospitalier du Rouvray, Rouen, France

UFR Santé, Université de Rouen Normandie, Rouen, France

Olivier Guillin

Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands

Sinan Gülöksüz, Jurjen J. Luykx, Bart P. F. Rutten, Therese van Amelsvoort, Ruud van Winkel, Therese van Amelsvoort & Ruud van Winkel

Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA

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Department of Psychiatry, Faculty of Medicine and Biomedical Research Centre (CIBM), University of Granada, Granada, Spain

Blanca Gutiérrez

Department of Psychiatry, Charité - Universitätsmedizin, Berlin, Germany

Children’s Hospital of Philadelphia, Leonard Madlyn Abramson Research Center, Philadelphia, PA, USA

Hakon Hakonarson & Renata Pellegrino

Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA

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Mental Illness Research Clinical and Education Center (MIRECC), JJ Peters VA Medical Center, New York, NY, USA

NorthWestern Mental Health, Melbourne, Victoria, Australia

Carol Harvey & Christos Pantelis

MRC Human Genetics Unit, University of Edinburgh, Institute of Genetics and Cancer, Western General Hospital, Edinburgh, UK

Caroline Hayward

School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia

Frans A. Henskens & Brian J. Kelly

Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland

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Broad Institute of MIT and Harvard, Cambridge, MA, USA

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Department of Psychiatry, Fujita Health University School of Medicine, Toyoake Aichi, Japan

Masashi Ikeda & Nakao Iwata

Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

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Regional Centre for Clinical Research in Psychosis, Department of Psychiatry, Stavanger University Hospital, Stavanger, Norway

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Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffman-La Roche, Basel, Switzerland

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Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan

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Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

Department of Medical Genetics, Medical University, Sofia, Bulgaria

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Institute of Molecular Genetics of National Research Centre “Kurchatov Institute”, Moscow, Russia

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Latvian Biomedical Research and Study Centre, Riga, Latvia

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Mental Health Research Center, Moscow, Russian Federation

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Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany

Julia Kraft

RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

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Faculty of Medicine, Vilnius University, Vilnius, Lithuania

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Psychiatry Department, University of Indonesia - Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia

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Department of Psychiatry, 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic

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Dipartimento di Biologia, Universita’ di Pisa, Pisa, Italy

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Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA

Laura C. Lazzeroni & Douglas F. Levinson

Department of Biomedical Data Science, Stanford University, Stanford, CA, USA

Laura C. Lazzeroni

Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry and Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

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Department of Psychiatry, Wright State University, Dayton, OH, USA

Douglas S. Lehrer

Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

Bernard Lerer

Zhongshan School of Medicine and Key Laboratory of Tropical Diseases Control (SYSU), Sun Yat-sen University, Guangzhou, China

Department of Psychiatry, Columbia University, New York, NY, USA

Jeffrey Lieberman & T. Scott Stroup

VISN 22, Mental Illness Research, Education and Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA, USA

Gregory A. Light & David Braff

Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan

Chih-Min Liu

Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, Taiwan

Chih-Min Liu & Hai-Gwo Hwu

Mental Health Unit, Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland

Jouko Lönnqvist

Department of Psychiatry, University of Helsinki, Helsinki, Finland

Hunter New England Health and University of Newcastle, Newcastle, New South Wales, Australia

Carmel M. Loughland

Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Szczecin, Poland

Jan Lubinski

Department of Psychiatry, UMC Utrecht Brain Center, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands

Jurjen J. Luykx, Steven Bakker & René Kahn

Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

Jurjen J. Luykx

Second Opinion Outpatient Clinic, GGNet Mental Health, Warnsveld, The Netherlands

Department of Biology and Medical Genetics, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic

Milan Macek Jr

Black Dog Institute, University of New South Wales, Randwick, New South Wales, Australia

Andrew Mackinnon

Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia

Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA

Brion S. Maher

Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany

Wolfgang Maier

Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA

Dolores Malaspina & Eşref Cem Atbaşoğlu

Asfalia Biologics, iPEPS-ICM, Hôpital Universitaire de la Pitié-Salpêtrière, Paris, France

Jacques Mallet

Semel Institute for Neurosciene, University of California Los Angeles, Los Angeles, CA, USA

Stephen R. Marder

Department of Medicine, Harvard Medical School, Boston, MA, USA

Alicia R. Martin & Hailiang Huang

Hospital Universitari Institut Pere Mata, IISPV, Universitat Rovira i Virgili, CIBERSAM, Reus, Spain

Lourdes Martorell, Gerard Muntané & Elisabet Vilella

Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada

Manuel Mattheisen & Sandra Meier

Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada

Manuel Mattheisen

Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany

Manuel Mattheisen & Thomas G. Schulze

VA Boston Health Care System, Brockton, MA, USA

Robert W. McCarley

Centre for Neuroimaging, Cognition and Genomics (NICOG), National University of Ireland Galway, Galway, Ireland

Colm McDonald, Gary Donohoe & Derek W. Morris

Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia

John J. McGrath, Sathish Periyasamy, Bryan J. Mowry & Naomi R. Wray

Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Brisbane, Queensland, Australia

John J. McGrath

Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

Helena Medeiros & Janet L. Sobell

College of Medicine, SUNY Downstate Health Sciences University, New York, NY, USA

Helena Medeiros

Department of Biomedicine, Aarhus University, Aarhus, Denmark

Sandra Meier

Department of Medical Genetics, University of Pécs, School of Medicine, Pécs, Hungary

Bela Melegh

Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, MA, USA

Raquelle I. Mesholam-Gately & Larry J. Seidman

Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia

Andres Metspalu, Lili Milani & Tõnu Esko

School of Psychology, University of Newcastle, Newcastle, New South Wales, Australia

Patricia T. Michie

Psychiatric Clinic, Alexandrovska University Hospital, Sofia, Bulgaria

Vihra Milanova

Department of Pharmacy, University of Oslo, Oslo, Norway

Espen Molden

Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway

Department of Nursing, Faculty of Health Sciences and Biomedical Research Centre (CIBM), University of Granada, Granada, Spain

Esther Molina

Department of Genetics, Faculty of Biological Sciences, Universidad de Valencia, Valencia, Spain

María Dolores Molto

Biomedical Research Institute INCLIVA, Valencia, Spain

María Dolores Molto & Julio Sanjuan

Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, UK

Valeria Mondelli

Departments of Public Health and Preventive Medicine, Family Medicine, and Psychiatry and Behavioral Sciences, State University of New York, Upstate Medical University, Syracuse, NY, USA

Christopher P. Morley

Institut de Biologia Evolutiva (UPF-CSIC), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, PRBB, Barcelona, Spain

Gerard Muntané

Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland

Kieran C. Murphy

Department for Neurosciences, Center for Contextual Psychiatry, KU Leuven, Leuven, Belgium

Inez Myin-Germeys

Cognitive Neuropsychiatry Laboratory, Department of Psychiatry and Psychotherapy, Philipps Universität Marburg, Marburg, Germany

Igor Nenadić

Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Gerald Nestadt & Ann E. Pulver

Centre for Public Health, Institute of Clinical Sciences, Queen’s University Belfast, Belfast, UK

F. Anthony O’Neill

Department of Statistics and Applied Probability, University of California at Santa Barbara, Santa Barbara, CA, USA

Sang-Yun Oh

Computational Research Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

Department of Psychiatry, University of Colorado Denver, Aurora, CO, USA

Ann Olincy & Robert Freedman

Department of Morphology and Genetics, Laboratorio de Genetica, Universidade Federal de São Paulo, São Paulo, Brazil

Vanessa Kiyomi Ota, Marcos Leite Santoro & Sintia Iole Belangero

Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Melbourne, Victoria, Australia

Christos Pantelis

The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia

Christos Pantelis & Bernhard T. Baune

Department of Psychiatry, Melbourne Medical School, University of Melbourne, Parkville, Victoria, Australia

Department of Public Health Solutions, Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland

Tiina Paunio

Department of Psychiatry and SleepWell Research Program, Faculty of Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

Queensland Centre for Mental Health Research, University of Queensland, Brisbane, Queensland, Australia

Sathish Periyasamy & Bryan J. Mowry

Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA

Diana O. Perkins & Patrick F. Sullivan

Clinic of Psychiatry and Psychotherapy, Weißer Hirsch, Dresden, Germany

Bruno Pfuhlmann

Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA

Olli Pietiläinen & Steven E. Hyman

Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland

Olli Pietiläinen, Christian Benner, Matti Pirinen, Aarno Palotie & Mark J. Daly

Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK

David Porteous

Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

John Powell

South London and Maudsley NHS Mental Health Foundation Trust, London, UK

Diego Quattrone & Marta Di Forti

Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK

Digby Quested

Department of Psychiatry, University of Oxford, Oxford, UK

Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA

Allen D. Radant & Debby W. Tsuang

VA Puget Sound Health Care System, Seattle, WA, USA

Huntsman Mental Health Institute, Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA

Mark H. Rapaport

SUNY Upstate Medical University, Syracuse, NY, USA

Cheryl Roe & Chunyu Liu

Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA

Joshua L. Roffman & Jennifer L. Moran

Department of Psychiatry, Psychosomatics and Psychotherapy, Julius-Maximilians-Universität Würzburg, Würzburg, Germany

Julian Roth & Micha Gawlik

Généthon, Evry, France

Safaa Saker-Delye

THL–Finnish Institute for Health and Welfare, Helsinki, Finland

Veikko Salomaa & Jaana Suvisaari

Department of Psychiatry, School of Medicine, University of Valencia, Hospital Clínico Universitario de Valencia, Valencia, Spain

Julio Sanjuan

Priority Centre for Brain and Mental Health Research, University of Newcastle, Mater Hospital, McAuley Centre, Newcastle, New South Wales, Australia

Ulrich Schall

Division of Molecular Medicine, NSW Health Pathology North, Newcastle, New South Wales, Australia

Rodney J. Scott

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

Jianxin Shi

James J. Peters VA Medical Center, Bronx, NY, USA

Larry J. Siever & Jeremy M. Silverman

Faculty of Medicine, University of Iceland, Reykjavik, Iceland

Engilbert Sigurdsson

Department of Psychiatry, Landspitali University Hospital, Reykjavik, Iceland

West Region, Institute of Mental Health, Singapore, Singapore

Yoo Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore

School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China

Hon-Cheong So

Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong, China

School of Social and Health Sciences, Leeds Trinity University, Leeds, UK

Helen J. Stain

TIPS - Network for Clinical Research in Psychosis, Stavanger University Hospital, Stavanger, Norway

NORMENT Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway

Nils Eiel Steen & Erik G. Jönsson

Department of Neurology, Medical University of Vienna, Vienna, Austria

Elisabeth Stögmann & Fritz Zimprich

Harvard Medical School Department of Psychiatry at Beth Israel Deaconess Medical Center, Boston, MA, USA

William S. Stone

Massachusetts Mental Health Center, Boston, MA, USA

Lieber Institute for Brain Development, Baltimore, MD, USA

Richard E. Straub, Thomas Hyde, Andrew Jaffe & Daniel R. Weinberger

Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands

Eric Strengman

Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA

Catherine A. Sugar

Department of Psychiatry, Washington University, St Louis, MO, USA

Dragan M. Svrakic & C. Robert Cloninger

Department of Psychiatry, Charité – Universitätsmedizin Berlin, Berlin, Germany

Thi Minh Tam Ta

Berlin Institute of Health (BIH), Berlin, Germany

Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

Atsushi Takahashi & Chikashi Terao

Université de Paris, Faculté de Médecine, Hôpital Cochin-Tarnier, Paris, France

Florence Thibaut

INSERM U1266, Institut de Psychiatrie et de Neurosciences, Paris, France

Bulgarian Academy of Science, Sofia, Bulgaria

Draga Toncheva

Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy

Sarah Tosato

Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy

Gian Battista Tura

Department of Psychiatry, Faculty of Medicine, Istanbul University, Istanbul, Turkey

Division of Mental Health, St. Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway

Arne Vaaler

Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway

Department of Neurosciences, Center for Clinical Psychiatry, KU Leuven, Leuven, Belgium

Ruud van Winkel

Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland

Juha Veijola & Ruud van Winkel

Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland

Juha Veijola

Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland

John Waddington

Neuropsychiatric Epidemiology Research Unit, School of Population and Global Health, University of Western Australia, Perth, Western Australia, Australia

Anna Waterreus & Vera A. Morgan

Centre for Clinical Research in Neuropsychiatry, University of Western Australia, Perth, Western Australia, Australia

Anna Waterreus, Assen V. Jablensky & Vera A. Morgan

Sheba Medical Center, Tel Hashomer, Israel

Mark Weiser

Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia

Jing Qin Wu

Department of Psychiatry, GGz Centraal, Utrecht, The Netherlands

Stanley Neurovirology Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Robert Yolken

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

Clement C. Zai & James L. Kennedy

Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

Department of Psychiatry, School of Medicine, Ankara University, Ankara, Turkey

Eşref Cem Atbaşoğlu & Meram C. Saka

Department of Psychiatry, Queens University Kingston, Kingston, Ontario, Canada

Muhammad Ayub

Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA

Donald W. Black

School of Nursing, Louisiana State University Health Sciences Center, New Orleans, LA, USA

Nancy G. Buccola

Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA

William F. Byerley

Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan Town, Taiwan

Wei J. Chen

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan

University of Sevilla, CIBERSAM IBiS, Seville, Spain

Benedicto Crespo-Facorro

Hospital Universitario Virgen del Rocio, Department of Psychiatry, Universidad del Sevilla, Seville, Spain

Discipline of Psychiatry, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia

Cherrie Galletly

Ramsay Health Care (SA) Mental Health, Adelaide, South Australia, Australia

Northern Adelaide Local Health Network, Adelaide, South Australia, Australia

Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy

Massimo Gennarelli

Genetic Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy

Department of Psychiatry, College of Medicine and National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan

Hai-Gwo Hwu

Psychosis Research Unit, Aarhus University Hospital, Aarhus, Denmark

Max Planck Institute of Psychiatry, Munich, Germany

Bertram Müller-Myhsok

Munich Cluster for Systems Neurology, Munich, Germany

Department of Health Data Science, University of Liverpool, Liverpool, UK

Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia

Amanda L. Neil

Mental Health Services in the Capital Region of Denmark, Mental Health Center Copenhagen, University of Copenhagen, Copenhagen, Denmark

Merete Nordentoft

Rutgers University, Robert Wood Johnson Medical School, New Brunswick, NJ, USA

Michele T. Pato & Carlos N. Pato

Rutgers University, New Jersey Medical School, Newark, NJ, USA

Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland

Matti Pirinen

Department of Public Health, University of Helsinki, Helsinki, Finland

Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA

Thomas G. Schulze

Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany

Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University, Baltimore, MD, USA

Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA

Eli A. Stahl & Tõnu Esko

Regeneron Genetics Center, Orange, CA, USA

Eli A. Stahl

College of Public Health, China Medical University, Taichung, Taiwan

Shi-Heng Wang

State Key Laboratory of Genetic Engineering and Ministry of Education (MOE) Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, China

School of Life Science and Technology, ShanghaiTech University, Shanghai, China

Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China

Department of Clinical Sciences, Psychiatry, Umeå University, Umeå, Sweden

Rolf Adolfsson

Division of Psychiatry, Department of Mental Health Neuroscience, University College London, London, UK

Elvira Bramon

Department of Psychiatry, San Cecilio University Hospital, University of Granada, Granada, Spain

Jorge A. Cervilla

Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland

Sven Cichon

Department of Biomedicine, University of Basel, Basel, Switzerland

Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany

Eli Lilly and Company, Windlesham, UK

David A. Collier & David A. Collier

Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, Dublin, Ireland

Aiden Corvin & Michael Gill

UCL Genetics Institute, University College London, London, UK

David Curtis

Centre for Psychiatry, Queen Mary University London, London, UK

Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy

Enrico Domenici

Dementia Research Institute, Cardiff University, Cardiff, UK

Valentina Escott-Price

Department of Psychiatry, Phoenix VA Healthcare System, Phoenix, AZ, USA

Ayman H. Fanous

Banner-University Medical Center, Phoenix, AZ, USA

Department of Human Molecular Genetics of the Institute of Biochemistry and Genetics of the Ufa Federal Research Center of the Russian Academy of Sciences (IBG UFRC RAS), Ufa, Russia

Anna Gareeva, Elza Khusnutdinova & Anna Gareeva

Federal State Educational Institution of Highest Education Bashkir State Medical University of Public Health Ministry of Russian Federation (BSMU), Ufa, Russia

Psychiatric Genetic Epidemiology and Neurobiology Laboratory (PsychGENe lab), Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA

Stephen J. Glatt

Department of Psychiatry, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea

Kyung Sue Hong

Department of Psychiatry and Zilkha Neurogenetics Institute, Keck School of Medicine at University of Southern California, Los Angeles, CA, USA

James A. Knowles

Department of Cell Biology, State University of New York, Downstate Health Sciences University, New York, NY, USA

Department of Psychosis, Institute of Mental Health, Singapore, Singapore

Neuroscience and Mental Health, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore

Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, NY, USA

Todd Lencz & Anil K. Malhotra

Department of Psychiatry, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA

Human Genetics, Genome Institute of Singapore, A*STAR, Singapore, Singapore

Jianjun Liu

Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffman-La Roche, Basel, Switzerland

Dheeraj Malhotra

Department of Preventative Medicine, Faculdade de Medicina FMUSP, University of São Paulo, São Paulo, Brazil

Paulo R. Menezes

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA

Vishwajit Nimgaonkar

Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA

Roel A. Ophoff

Department of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands

Early Clinical Development, Pfizer Worldwide Research and Development, Groton, CT, USA

Sara A. Paciga

Analytic and Translational Genetics Unit, Department of Medicine, Department of Neurology and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA

Aarno Palotie

Aarno Palotie & Stephan Ripke

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Shengying Qin

Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, University of Granada, Granada, Spain

Margarita Rivera

Institute of Neurosciences, Biomedical Research Center (CIBM), University of Granada, Granada, Spain

Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, New South Wales, Australia

Sibylle G. Schwab

Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia

Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy

Alessandro Serretti

Centre for PanorOmic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China

Pak C. Sham & Pak C. Sham

State Key Laboratory of Brain and Cognitive Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China

Department of Psychiatry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China

Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK

David St Clair

Center for Behavioral Genomics, Department of Psychiatry, University of California San Diego, La Jolla, CA, USA

Ming T. Tsuang

Institute of Genomic Medicine, University of California San Diego, La Jolla, CA, USA

University Medical Center Utrecht, Department of Psychiatry, Utrecht, The Netherlands

Department of Psychiatry and Human Behavior, School of Medicine, University of California Irvine, Irvine, CA, USA

Marquis P. Vawter

Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, Copenhagen, Denmark

Thomas Werge

Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

Thomas Werge & David St Clair

Center for GeoGenetics, GLOBE Institute, University of Copenhagen, Copenhagen, Denmark

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark

Thomas Werge & Jim van Os

School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Western Australia, Australia

Dieter B. Wildenauer & Jim van Os

Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, China

Xin Yu & Weihua Yue

National Clinical Research Center for Mental Disorders, NHC Key Laboratory of Mental Health (Peking University) and Chinese Academy of Medical Sciences Research Unit, Beijing, China

PKU–IDG/McGovern Institute for Brain Research, Peking University, Beijing, China

Mental Illness Research, Education, and Clinical Center (VISN 2 South), James J. Peters VA Medical Center, New York, NY, USA

Panos Roussos

Oxford Health NHS Foundation Trust, Oxford, UK

Evangelos Vassos

Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research, University Medical Center Amsterdam, Amsterdam, The Netherlands

Matthijs Verhage

Department of Functional Genomics, Faculty of Exact Science, Center for Neurogenomics and Cognitive Research, VU University Amsterdam and VU Medical Center, Amsterdam, The Netherlands

Frank Koopmans, Dnyanada Sahasrabudhe, Ruud F. Toonen, Matthijs Verhage, Matthijs Verhage & Danielle Posthuma

Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China

Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, Western Australia, Australia

Nan Dai, Qin Wenwen & D. B. Wildenauer

School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia, Australia

Department of Psychiatry, University of Indonesia, Jakarta, Indonesia

Feranindhya Agiananda, Nurmiati Amir, Ronald Antoni, Tiana Arsianti, Asmarahadi Asmarahadi, H. Diatri, Prianto Djatmiko, Irmansyah Irmansyah, Siti Khalimah, Irmia Kusumadewi, Profitasari Kusumaningrum, Petrin R. Lukman, Martina W. Nasrun, N. S. Safyuni, Prasetyawan Prasetyawan, G. Semen, Kristiana Siste, Heriani Tobing, Natalia Widiasih, Tjhin Wiguna, D. Wulandari, None Evalina, A. J. Hananto, Joni H. Ismoyo, T. M. Marini, Supiyani Henuhili, Muhammad Reza & Suzy Yusnadewi

Mayo Clinic, Rochester, MN, USA

• Alexej Abyzov

Mount Sinai, New York, NY, USA

Schahram Akbarian, Harm van Bakel, Michael Breen, Alex Charney, Stella Dracheva, Kiran Girdhar, Gabriel Hoffman, Yan Jiang, Dalila Pinto, Shaun Purcell, Panagiotis Roussos & Jennifer Wiseman

Duke University, Durham, NC, USA

Allison Ashley-Koch, Gregory Crawford & Tim Reddy

University of Chicago, Chicago, IL, USA

Miguel Brown & Kay Grennan

Karolinska Institutet, Stockholm, Sweden

Julien Bryois

Yale University, New Haven, CT, USA

Becky Carlyle, Prashant Emani, Timur Galeev, Mark Gerstein, Mengting Gu, Brittney Guerra, Gamze Gursoy, Robert Kitchen, Donghoon Lee, Mingfeng Li, Shuang Liu, Fabio Navarro, Xinghua Pan, Sirisha Pochareddy, Joel Rozowsky, Nenad Sestan, Anurag Sethi, Xu Shi, Anna Szekely, Daifeng Wang, Jonathan Warrell, Sherman Weissman, Feinan Wu & Xuming Xu

University of Southern California, Los Angeles, CA, USA

Gerard Coetzee, Peggy Farnham, Fides Lay, Suhn Rhie, Heather Witt, Shannon Wood & Lijing Yao

University of California Los Angeles, Los Angeles, CA, USA

Mike Gandal, Damon Polioudakis, Vivek Swarup & Hyejung Won

University of Illinois at Chicago, Chicago, IL, USA

Gina Giase, Shan Jiang, Amira Kefi & Annie Shieh

Johns Hopkins University, Baltimore, MD, USA

Fernando Goes & Peter Zandi

University of North Carolina - Chapel Hill, Chapel Hill, NC, USA

Yunjung Kim

SUNY Downstate Medical Center, New York, NY, USA

University of Massachusetts, Amherst, MA, USA

Eugenio Mattei, Michael Purcaro & Henry Pratt

Sage Bionetworks, Seattle, WA, USA

Mette A. Peters

University of California San Francisco, San Francisco, CA, USA

Stephan Sanders

University of Massachusetts Medical School, Worcester, MA, USA

Zhiping Weng

Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

Kevin White

King’s College London, London, UK

Maria J. Arranz, Elvira Bramon, Conrad Iyegbe, Cathryn Lewis, Kuang Lin, Robin M. Murray, John Powell & Muriel Walshe

Fundació de Docència i Recerca Mútua de Terrassa, Universitat de Barcelona, Barcelona, Spain

• Maria J. Arranz

Child and Adolescent Psychiatry, University of Technology Dresden, Dresden, Germany

Stephan Bender

Section for Experimental Psychopathology, General Psychiatry, Heidelberg, Germany

Stephan Bender & Matthias Weisbrod

Institute of Cognitive Neuroscience, University College London, London, UK

University Hospital Marqués de Valdecilla, Instituto de Formación e Investigación Marqués de Valdecilla, University of Cantabria, Santander, Spain

Benedicto Crepo-Facorro & Ignacio Mata

Neuroscience and Mental Health Research Institute, Division of Psychiatry and Clinical Neuroscience, Cardiff University, Cardiff, UK

Jeremy Hall

Division of Psychiatry, University of Edinburgh, Edinburgh, UK

Stephen Lawrie & Andrew McIntosh

Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Don H. Linszen

Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht, The Netherlands

Institute of Psychiatry, King’s College London, London, UK

Department of Psychiatry, University of Halle, Halle, Germany

Dan Rujescu

Department of Psychiatry, University of Munich, Munich, Germany

Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland

Tilmann Achsel & Claudia Bagni

RG Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg, Germany

Maria Andres-Alonso & Michael R. Kreutz

Molecular Physiology of the Synapse Laboratory, Biomedical Research Institute Sant Pau, Barcelona, Spain

Department of Neurology, Yale School of Medicine, New Haven, CT, USA

Thomas Biederer

Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany

LSI Neurobiology Programme, National University of, Singapore, Singapore

John Jia En Chua

Zilkha Neurogenetic Institute and Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

Marcelo P. Coba

Functional Genomics section, Department of Human Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam University Medical Center, Amsterdam, The Netherlands

L. Niels Cornelisse & Jan R. T. van Weering

Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands

Arthur P. H. de Jong & Harold D. MacGillavry

Sorbonne Université, Institut du Cerveau ‐ Paris Brain Institute ‐ ICM, Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière, Paris, France

Jaime de Juan-Sanz

Institute for Pharmacology and Toxicology, Medical Faculty Otto-von-Guericke University Magdeburg, Magdeburg, Germany

Daniela C. Dieterich, Rainer Pielot & Karl-Heinz Smalla

Leibniz Institute for Neurobiology (LIN), Magdeburg, Germany

Daniela C. Dieterich, Eckart D. Gundelfinger, Rainer Pielot & Karl-Heinz Smalla

McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA

Guoping Feng

Solomon H. Snyder Department of Neuroscience, Kavli Neuroscience Discovery Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

Hana L. Goldschmidt & Richard L. Huganir

Department of Neuroscience, Genentech, South San Francisco, CA, USA

Casper Hoogenraad

Steven E. Hyman

Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark

Cordelia Imig

Laboratory of Neurobiology, Max-Planck Institute for Biophysical Chemistry, Göttingen, Germany

Reinhard Jahn

Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea

Hwajin Jung & Eunjoon Kim

Department of Neurobiology, Harvard Medical School, Boston, MA, USA

Pascal S. Kaeser

Department of Molecular Physiology and Cell Biology, Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany

Noa Lipstein

Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA

Robert Malenka

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Québec, Canada

Peter S. McPherson

Biological Sciences, University of Southampton, Southampton, UK

Vincent O’Connor

Department of Biochemistry, Weill Cornell Medicine, New York, NY, USA

Timothy A. Ryan

CNR Neuroscience Institute, Milan, Italy

Carlo Sala & Chiara Verpelli

Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

August B. Smit

Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA

Thomas C. Südhof

Division of Bioinformatics, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA

Paul D. Thomas

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•  & Michael C. O’Donovan

Contributions

The management group for this paper was led by M.O.D. and J.T.R.W., with S.R. responsible for primary analytic matters supported by B.M.N. and M.J.D. The management group comprised a subset of the principal investigators of the component studies, bioinformaticians and analysts and was responsible for study design, conduct, management, primary and final interpretation; this group included O.A.A., B.T.B., S.I.B., A.D.B., D.B., E.B., S.C., A. Corvin, D. Curtis, M.J.D., M.D.F., E.D., H.E., A.H.F., P.V.G., M. Gill, S.J.G., K.S.H., H. Huang, N.I., R.S.K., K.S.K., J.A.K., J. Lee, T.L., D.F.L., J. Liu, A. McIntosh, A. McQuillin, V.A.M., D.W.M., B.J.M., B.M.N., M.O.D., R.A.O., M.J.O., A.P., D. Posthuma, S.Q., B.P.R., S.R., D.R., S.G.S., A. Serretti, Y.S., E.A.S., P.F.S., M.T.T., M.P.V., J.T.R.W., D.R.W., T.W., N.R.W., X.Y. and W.Y. GWAS meta-analyses: S.A., G.P., S.R. and V.T. Replication data: S. Magnusson, H.S. and K. Stefansson (deCODE). African American and Latino sample analyses: E.G.A., T.B., G.G., S.R. and V.T. Bioinformatics: J. Bryois, J.C.H., A.F.P., A.J.P., D. Posthuma, P.F.S., K.W. and the SynGO consortium. Comparison of male and female individuals: S.R., J. Sidorenko, V.T. and P.M.V. Heritability and polygenic prediction: O.A.A., O.F., T.G., H. Huang, B.M.N., M.O.D., A.F.P., A.L.R., S.R., V.T., J.T.R.W., N.R.W. and J.Z. Phenotype stratification: C.A.D. and E. Vassos. Cellular and tissue analysis: J. Bryois, M.O.D., D. Posthuma, P.F.S., J.T.R.W. and K.W. Gene Ontology: J.C.H., M.O.D., A.F.P., A.J.P., D. Posthuma, J.T.R.W. and K.W. Fine-mapping: C.B., M.J.D., H. Huang, M. Lam, M.O.D., G.P., A.F.P., M.P., S.R. and J.T.R.W. SMR: L.S.H., M.O.D., T.Q., N.R.W., Y.W. and J.Y. Hi-C: D. Posthuma, A.L.R., P.F.S., J.T.R.W. and K.W. Other transcriptome-wide association studies: M.J.G., L.S.H., M. Kim, P.R., G.V. and W. Zhang. Integration of fine-mapping, gene expression, Hi-C informatics and rare variants: L.S.H., M.O.D., A.F.P., T.Q., A.L.R., P.F.S., J.T.R.W., N.R.W., Y.W. and J.Y. SynGO: F.K., M.O.D., A.F.P., A.B.S., M.V. and J.T.R.W. Additional statistical advice: P.A.H. The remaining authors contributed to the recruitment, phenotyping, genotyping or data processing for the contributing components of the meta-analysis, or provided other forms of functional annotation data. Primary drafting and editing of the manuscript were coordinated by S.R., J.T.R.W. and M.O.D. The primary draft sections were written by J. Bryois, C.Y.C., C.A.D., L.S.H., H. Huang, B.M.N., M.O.D., M.J.O., A.F.P., A.J.P., S.R., A.B.S, P.F.S., V.T., E. Vassos, M.V., J.T.R.W., N.R.W. and J.Y. Additional edits were from O.A.A., M.J.D. and K.S.K. Numerous other authors provided edits, comments and suggestions, and all authors saw and approved the contents of the manuscript. The Chair of the PGC is P.F.S. and the Schizophrenia Working Group of the PGC is led by M.O.D. and J.T.R.W.

Corresponding authors

Correspondence to Stephan Ripke , James T. R. Walters or Michael C. O’Donovan .

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A. Palotie is a member of Astra Zeneca’s Genomics Advisory Board. V. Salomaa has consulted for Novo Nordisk and Sanofi and has ongoing research collaboration with Bayer (both unrelated to the present study). M. F. Green is a paid consultant for AiCure, Biogen, Lundbeck and Roche, is a member of the Scientific Board of Cadent, and has received research funds from Forum. G. A. Light has consulted to Astellas, Forum, and Neuroverse. K. Nuechterlein has research support from Janssen, Genentech and Brain Plasticity, and has also consulted for Astellas, MedinCell, Takeda, Teva, Genentech, Otsuka, Janssen and Brain Plasticity. D. Cohen has reported past consultation for or the receipt of honoraria from Otsuka, Shire, Lundbeck, Roche and Janssen. M. J. Daly is a founder of Maze Therapeutics and on the scientific advisory board of Neumora Therapeutics. A. K. Malhotra is a consultant to Genomind, InformedDNA and Concert Pharmaceuticals. R. A. Bressan has received research grants from Janssen, has been a forum consultant for Janssen, Sanof and Roche and is on the speakers’ bureau for Ache, Janssen, Sanofi and Torrent. C. Noto was on the speakers’ bureau and/or has acted as a consultant for Janssen and Daiichi-Sankyo in the last 12 months. C. Pantelis has, for the last three years, served on an advisory board for Lundbeck and received honoraria for talks presented at educational meetings organized by Lundbeck. D. A. Collier is a full-time employee and stockholder of Eli Lilly and Company. M. C. O’Donovan is supported by a collaborative research grant from Takeda Pharmaceuticals. M. J. Owen is supported by a collaborative research grant from Takeda Pharmaceuticals. J. T. R. Walters is supported by a collaborative research grant from Takeda Pharmaceuticals. A. J. Pocklington is supported by a collaborative research grant from Takeda Pharmaceuticals. S. R. Marder has consulted for the following companies: Roche, Sunovion, Lundbeck, Boeringer-Ingelheim, Acadia and Merck. S. Gopal is a full time employee and shareholder in Johnson & Johnson (AMEX: JNJ). A. Savitz is an employee of Janssen Research & Development and owns stock or stock options in the company. Q. S. Li is an employee of Janssen Research & Development and owns stock or stock options in the company. T. Kam-Thong is an employee of F. Hoffman-La Roche. A. Rautanen is an employee of F. Hoffman-La Roche. D. Malhotra is an employee of F. Hoffman-La Roche. S. A. Paciga is an employee of Pfizer. O. A. Andreassen is a consultant for HealthLytix, and received speaker’s honorarium from Lundbeck. S. V. Faraone has received income, potential income, travel expenses continuing education support and/or research support from Akili Interactive Labs, Arbor, Genomind, Ironshore, Ondosis, Otsuka, Rhodes, Shire/Takeda, Sunovion, Supernus, Tris and Vallon. With his institution, he has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of attention deficit hyperactivity disorder. In previous years, he received support from Alcobra, Aveksham, CogCubed, Eli Lilly, Enzymotec, Impact, Janssen, KemPharm, Lundbeck/Takeda, McNeil, Neurolifesciences, Neurovance, Novartis, Pfizer and Vaya. He also receives royalties from books published by Guilford Press: Straight Talk about Your Child’s Mental Health; Oxford University Press: Schizophrenia: The Facts; and Elsevier: ADHD: Non-Pharmacologic Interventions. He is also Program Director of https://adhdinadults.com/ . C. Arango has been a consultant to or has received honoraria or grants from Acadia, Angelini, Gedeon Richter, Janssen Cilag, Lundbeck, Minerva, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. K. Alptekin has received grants and honoraria for consulting work, lecturing and research from Abdi İbrahim, Abdi İbrahim Otsuka, Janssen, Ali Raif and TUBITAK.

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Extended data figures and tables

Extended data fig. 1 primary gwas manhattan plot..

The x axis indicates chromosomal position and the y axis is the significance of association (−log 10 ( P )). The red line represents genome-wide significance level (5 × 10 −8 ). SNPs in green are in linkage disequilibrium (LD; r 2  > 0.1) with index SNPs (diamonds) which represent LD-independent genome-wide significant associations.

Extended Data Fig. 2 Polygenic risk prediction.

a , Distributions of liability scale R 2 across 98 left-out-cohorts for polygenic risk scores built from SNPs with different p-value thresholds. Distributions of liability R 2 (assuming schizophrenia life-time risk of 1%) are shown for each p-value threshold, with point size representing size of the left-out cohort and colour representing ancestry. The median liability R 2 is represented as a horizontal black line. b , Liability R 2 of predicted and observed phenotypes in left-out cohorts using variants with p-value threshold p = 0.05, from the fixed effect meta-analysis of variant effects, unadjusted for multiple comparisons. The polygenic risk scores are derived from two separate sets of leave-one-out GWAS meta-analyses: y axis R 2 based on the results of primary GWAS including all ancestries; x axis R 2 based on cohorts of the same ancestry as the test samples. Circles denote core PGC samples. Triangles denote African American and Latino samples processed external to PGC by the providing author.

Extended Data Fig. 3 Association between 37 human tissues and schizophrenia.

The mean of the evidence (-log 10 P ) obtained from two methods (MAGMA, LDSC) for testing GWAS data for enrichment of association in genes with high expression in each tissue as determined from bulk RNA-seq 14 . The bar colour indicates whether gene expression in the tissue is significantly associated with both methods, one method or none. The black vertical line represents the significance threshold corrected for the total number of tissues tested in this experiment. We also analysed previous waves of PGC schizophrenia GWAS 11 , 15 for comparison.

Supplementary information

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The main supplementary information document, containing the Supplementary Note; all supplementary figure legends; supplementary figures 3–5, 8, 9, 11, 12; and cohort descriptions.

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Peer review file, supplementary figure 1a, supplementary figure 1b, supplementary figure 2a, supplementary figure 2b, supplementary figure 6, supplementary figure 7, supplementary figure 10, supplementary tables.

This zip folder contains excel workbooks for all Supplementary Tables (1–29).

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Trubetskoy, V., Pardiñas, A.F., Qi, T. et al. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature 604 , 502–508 (2022). https://doi.org/10.1038/s41586-022-04434-5

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Published : 08 April 2022

Issue Date : 21 April 2022

DOI : https://doi.org/10.1038/s41586-022-04434-5

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Actor Taye Diggs Talks About Another Role: Caregiver for His Sister With Schizophrenia

The Broadway, film, and TV actor shares the story of his sister’s mental illness for the first time on World Schizophrenia Awareness Day.

For actor Taye Diggs, who’s had leading roles on Broadway, in films like How Stella Got Her Groove Back , and most recently in The CW Network’s All American , schizophrenia hit home in 2006. His younger sister Christian was diagnosed with the mental disorder that year, leaving the family floored and Christian, then 28, struggling as “my world fell out from underneath me,” she says.

Diggs is sharing the story of his sister’s diagnosis for the first time this World Schizophrenia Awareness Day (May 24), and also as part of both Mental Health Awareness Month and Bristol Myers Squibb’s new Live Your PosSCZible campaign , which aims to highlight stories of people living with schizophrenia as well as their care partners.

What led to Christian’s diagnosis?

Christian was someone who was joyful, a dancer, into socializing and suddenly she was withdrawn, she wasn’t connecting with family or sharing what was going on. We finally got her checked out.

How did the diagnosis and treatment affect you and your other three siblings?

The diagnosis was such a blow to us. It came out of nowhere. I was taken aback. I didn’t know how to react. I’m the big brother. In a moment like this I’m supposed to figure things out. I froze. I didn’t know what to do. My siblings were always close to each other, they had their own language, but this became an opportunity for us all to come together to support her. She found a psychiatrist and got on medication.

You’ve been one of her caregivers. How have you been helping her, and how has that affected you personally?

I’ve found that what Christian values most is me, us, connecting with her, and our being patient. I remind her how proud I am of her. The illness is complicated. How I help depends on what’s going on. I’ve been in contact with her psychiatrist when needed. Mostly it’s about being available for whatever is needed. When we first got the diagnosis, I thought of the stereotypes I knew from screens. Could she go out with me to a restaurant, or would she act out? It was important to spend time with her. I discovered how much of her life she was still able to live. Don’t assume the worst.

What have been some of the challenges regarding treatment for your sister and the family?

She had to figure out what she needed to alter. Once she got the right meds, stayed in therapy — as long as she did A, B, C, and D, she was good. She didn’t really struggle with staying on medication. Christian was on a mission. She is a testament that you can have a great life if you make adjustments.

What advice would you give to families or individuals who have a loved one with a mental illness or who is otherwise suffering?

People need to know there is a light at the end of the tunnel. If your loved one does the work, the possibilities are endless. You have to find them support, that’s what helped Christian spread her wings and be able to fly. Keep encouraging them to do what they need to do. We were fortunate that Christian had a good attitude. She was 100 percent down for doing everything she needed to get better. That’s not always the case; some people don’t want to go to therapy or take medication.

How is she doing now?

On a scale of 1 to 10, with 10 being fantastic, she’s a 10. When I think back to what I thought her life would be like to where she is today, things have worked out. She is a carpenter and has her own apartment. I enjoy when me, my sister Shalom, and Christian all get together. For me as a big brother who helped raise them, to see them grow up to become capable, funny human beings, is awesome. I would be friends with Christian even if she wasn’t my sister.

Much to the delight of fans, your character Billy Baker just reappeared on All American after dying in season five. What other projects are you working on? What can we expect next?

Well, what am I free to talk about yet? I’m excited to be producing a couple of movies. On one project, I’m working again with Meagan Good. It’s great to reconnect, to see how far she has grown. After the pandemic and the strike, I’m just grateful to be working.

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Everyday Health follows strict sourcing guidelines to ensure the accuracy of its content, outlined in our editorial policy . We use only trustworthy sources, including peer-reviewed studies, board-certified medical experts, patients with lived experience, and information from top institutions.

• Schizophrenia. National Institute of Mental Health.
• Schizophrenia. Johns Hopkins Medicine.

Teens who use marijuana are more likely to suffer psychotic disorders, study finds

Teenagers who used cannabis within the last year had a dramatically higher rate of developing a psychotic disorder, according to a study published Wednesday. 

The study, led by researchers from the University of Toronto, found an 11 times higher risk of developing a psychotic disorder among teenagers who used cannabis compared with those who did not. When the analysis was limited to just emergency room visits and hospitalizations, there was a 27-fold increase in psychotic disorders in teenagers who had used the drug. 

“When I see youths with psychotic symptoms, they’re almost always using lots of cannabis,” said Dr. Leslie Hulvershorn, a child psychiatrist and chair of the psychiatry department at Indiana University who was not involved with the study. “It would be unusual to see someone present with psychotic symptoms to a hospital and not have smoked cannabis.”

The paper adds to the growing body of research that links cannabis to an increased risk of psychotic disorders, particularly in adolescence. Use of marijuana, particularly higher-potency products, has been linked to a variety of mental health disorders, including schizophrenia, anxiety and depression .

“I think that there’s enough evidence out there for us to give recommendations that teens probably shouldn’t be using cannabis,” said the study’s lead author, Andre McDonald, a postdoctoral research fellow at McMaster University in Hamilton, Ontario. “If we can somehow ask teens to delay their use until their brain has developed a little further, I think that would be good for public health.”

While most teenagers who use cannabis will not develop psychotic disorders, McDonald said, the findings are concerning given how debilitating these conditions can be. 

The new study, like previous research on marijuana and psychosis, does not directly prove that marijuana is causing psychotic disorders. While it’s possible that teens who were prone to develop psychotic disorders could have also been more likely to use cannabis, it’s unlikely because of how striking the association was, Hulvershorn said. 

“The magnitude of the effect here is just hard to believe that it’s not related to cannabis,” Hulvershorn said. 

There was no association between cannabis use and psychotic disorders in people ages 20 to 33. 

“There’s something about that stage of brain development that we haven’t yet fully characterized — where there’s a window of time where cannabis use may increase the risk of psychosis,” said Dr. Kevin Gray, a professor of psychiatry and director of addiction sciences at the Medical University of South Carolina who was not involved with the study. “This study really puts a fine point on delaying cannabis use until your 20s may mitigate one of the most potentially serious risks.”

The Biden administration has been moving toward rescheduling marijuana from Schedule I to the less dangerous Schedule III, which would also acknowledge its medical benefits at the federal level. While the potential change is expected later this year, cannabis is currently legal in 24 states for recreational use.

Marijuana use among high school students has remained steady in recent years. Nearly 1 in 3 12th graders reported using it in the previous year, according to the 2023 Monitoring the Future Survey, an annual survey that measures drug and alcohol use among adolescent students nationwide. 

The new research, published in the respected journal Psychological Medicine, includes data from over 11,000 teens and young adults who were ages 12 to 24 at the beginning of the study.

The authors pulled from the annual Canadian Community Health Survey, focusing on 2009 to 2012. Participants were then followed for up to nine years after the initial survey to track any visits they may have had to doctors or emergency rooms or any times they were admitted to hospitals.. 

Of the teens who were hospitalized or visited emergency rooms for psychotic disorders, roughly 5 in 6 had reported previous cannabis use.

“We see this replicated over and over again that there’s this developmental window of adolescence that’s very high-risk,” Gray said. 

It’s not completely clear why, he added, but one theory is that disruptions to the endocannabinoid system in adolescence may make psychotic symptoms more likely. The endocannabinoid system is a complex signaling system in the brain that marijuana targets. That could make it harder to distinguish reality from what is going on inside the head, leading to symptoms such as hallucinations. 

The authors did not specifically look at how the potency of marijuana products affected the risk of mental disorders, although previous research has found an increased risk .

Akshay Syal, M.D., is a medical fellow with the NBC News Health and Medical Unit. 

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5 myths about schizophrenia, according to a mental health expert: ‘Huge stigma’

For world schizophrenia day, a psychiatric nurse practitioner shares some of the most common misconceptions.

Heavy pot use linked to schizophrenia, particularly in young men: Study

Heather Bacchus, whose son was a heavy marijuana user and died by suicide, describes how his usage affected his life as a study finds young adult pot use is at an all-time high.

About 1% of Americans, or nearly 3.5 million people, are affected by schizophrenia — yet the mental disorder remains highly stigmatized and misunderstood, experts say.

The reason, according to Brooke Kempf, a psychiatric mental health nurse practitioner based in Indiana, is a general lack of knowledge about schizophrenia.

"People may see somebody hallucinating and think, ‘That is schizophrenia,’ when there's so much more to the illness," she told Fox News Digital in an interview. 

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"It’s important for people to recognize that schizophrenia is a diagnosed and treatable medical condition."

For World Schizophrenia Day, Kempf shared some of the most common myths and misconceptions surrounding the disorder.

Approximately 1% of Americans, or nearly 3.5 million people, are affected by schizophrenia — yet the mental disorder remains highly stigmatized and misunderstood, experts say. (iStock)

Here's a look at five. 

Myth No. 1: People with schizophrenia are violent

One of the greatest and "most harmful" myths is the notion that people living with schizophrenia are "scary" or "violent," Kempf said.

"There is a long history of conflating TV or movie characters who are behaving in odd, confusing or frightening ways with a diagnosis of schizophrenia," she said. 

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"However, we have to remember that these are made-up, dramatized situations. A diagnosis of schizophrenia doesn't have anything to do with what we see on the screen."

When patients with schizophrenia experience an acute episode — perhaps having delusions or hearing voices — they might behave differently than they typically would, sometimes seeming angry or violent.

"The person is likely experiencing something within themselves that they might be arguing about or responding to, but they aren't targeting anything toward another person," Kempf said.

When a patient with schizophrenia is experiencing an acute episode — perhaps having delusions or hearing voices — they might behave differently than they typically would, sometimes seeming angry or violent. (iStock)

When symptoms are managed with medication, "you would probably have no idea of their diagnosis," she noted.

"Through my long history of working in community mental health and hearing their stories, I know that people living with schizophrenia are good, caring, loving people," Kempf said. 

"They are more likely," she added, "to be the victim of a violent crime than the perpetrator of one."

Myth No. 2: People with schizophrenia have multiple personalities

There is a misconception that people with schizophrenia have multiple personalities, which could be because the Greek word "schizophrenia" means "split mind," Kempf noted.

"However, people with schizophrenia do not have split personalities," she said. 

MORE THAN HALF OF THOSE WITH MENTAL ILLNESS DON'T GET NEEDED CARE

"They might have different behavioral characteristics when they're ill and experiencing an episode, but it's not because they have a split personality."

Myth No. 3: People with schizophrenia are not intelligent

This assumption is completely false, according to Kempf.

"If the illness isn't well managed and continues to progress, or they have repeated relapses, patients will lose gray matter in their brains, and their cognitive function may decline," she told Fox News Digital.

"But that does not mean they're not intelligent."

One expert said she's worked with a multitude of "very successful individuals who also happen to live with schizophrenia." (iStock)

Some patients may experience cognitive decline in the early stages of the disease — referred to as the "prodromal phase," Kempf said — but early diagnosis and intervention can help prevent that.

Kempf said she has worked with a multitude of "very successful individuals who also happen to live with schizophrenia."

"People with schizophrenia do not have split personalities."

In many cases, she noted, people can no longer see the "highly intelligent individual" behind the disease .

"As long as individuals with schizophrenia get the proper treatment — ideally with a long-acting injectable (LAI) medication — they can keep their symptoms controlled and function very well," Kempf said. 

Myth No. 4: Symptoms of schizophrenia only involve hallucinations and delusions

Schizophrenia consists of what is clinically termed "positive" and "negative" symptoms, Kempf noted.

"Delusions and hallucinations, as well as changes in behavior and thoughts, are considered positive symptoms," she said. 

"Delusions and hallucinations, as well as changes in behavior and thoughts, are considered positive symptoms" of schizophrenia, the expert said.  (iStock)

Patients experiencing these symptoms may hear voices or have extra thoughts, delusions or fixed false beliefs, the expert explained. 

"Hallucinations are not just hearing voices," Kempf said. "They can occur in multiple ways based on our senses — seeing, hearing, smelling or feeling things."

Negative symptoms are when people lose interest in the world around them, withdraw or don't take an interest in everyday social interactions, according to Kempf. 

DISRUPTED SLEEP, PLUS NIGHTMARES COULD BE LINKED TO AUTOIMMUNE DISEASES, EXPERTS SAY

"Patients with schizophrenia may get labeled as ‘lazy,’ or they don't seem as put together," she said. "But it's not about laziness. The person's brain doesn't connect these things as being important."

People with schizophrenia may also experience what are referred to as "psychomotor" symptoms, Kempf said — they might seem abnormally slow, and their speech and thought processes can be somewhat delayed or disorganized.

"Unfortunately, if these negative symptoms continue and there isn't treatment, they can impact cognitive functioning."

Myth No. 5: People with schizophrenia require long-term or lifelong hospitalization

Hospitalization for a person experiencing acute schizophrenia symptoms is usually very short, according to Kempf. 

"For someone having an episode of schizophrenia, the average length of stay may be about five days."

"In an inpatient setting, for someone having an episode of schizophrenia, the average length of stay may be about five days," she said.

"If a patient doesn't respond to medication and can’t function safely on their own, they might have to go to a longer-term, higher-level setting."

CHICAGO NURSE IS FINALLY FREE OF COVID-19-RELATED PTSD AND DEPRESSION AFTER ELECTRICAL BRAIN TAPPING THERAPY

Today, health care providers aim to give people with schizophrenia community-based services so that they're able to function on their own, Kempf noted.

This might mean supporting them with employment services and housing opportunities to ensure that they have an affordable and safe place to live. 

"Some patients continue to live with their family members; some might live in a group home," Kempf said.

"People living with this disease deserve to be treated like human beings and with the same care we would provide someone diagnosed with a physical illness."

From a medical perspective, schizophrenia has different levels of severity, the expert noted. 

"But, again, if managed well, with early intervention, an individual can remain high-functioning and live independently," she said. 

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"Our goal is the least structured environment possible, enabling the person to live a normal life where they can work, grocery shop and drive on a day-to-day basis." 

Ultimately, Kempf said, schizophrenia should be viewed as a disease, not a choice. 

"While schizophrenia is a mental health diagnosis, it should be thought of no differently than a physical health diagnosis of diabetes, heart disease or kidney disease," an expert said. (iStock)

"While schizophrenia is a mental health diagnosis, it should be thought of no differently than a physical health diagnosis of diabetes , heart disease or kidney disease," she said.

"It just impacts a different organ: the brain."

Other brain disorders, such as epilepsy, tend to be more accepted by society, she said — but there is still a "huge stigma" surrounding diseases like schizophrenia, "probably because of the fear of the unknown."

"It is treatable, and both medication and support services are available," she told Fox News Digital. 

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"We all have a role to play in helping to dispel myths, foster understanding and reduce stigma," she continued. 

"People living with this disease deserve to be treated like human beings and with the same care we would provide someone diagnosed with a physical illness ."

For more Health articles, visit www.foxnews.com/health .

Melissa Rudy is health editor and a member of the lifestyle team at Fox News Digital. Story tips can be sent to [email protected].

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