Schizophrenia polygenic risk score and 20-year course of illness in psychotic disorders

AbstractUnderstanding whether and how the schizophrenia polygenic risk score (SZ PRS) predicts course of illness could improve diagnosis and prognostication in psychotic disorders. We tested whether the SZ PRS predicts symptoms, cognition, illness severity, and diagnostic changes over the 20 years following first admission. The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Patients were assessed six times over 20 years, and 249 provided DNA. Geographically- and demographically-matched never psychotic adults were recruited at year 20, and 205 provided DNA. Symptoms were rated using the Schedule for the Assessment of Positive Symptoms and Schedule for the Assessment of Negative Symptoms. Cognition was evaluated with a comprehensive neuropsychological battery. Illness severity and diagnosis were determined by consensus of study psychiatrists. SZ PRS was significantly higher in first-admission than never psychotic groups. Within the psychosis cohort, the SZ PRS predicted more severe negative symptoms (β = 0.21), greater illness severity (β = 0.28), and worse cognition (β = −0.35), across the follow-up. The SZ PRS was the strongest predictor of diagnostic shifts from affective to non-affective psychosis over the 20 years (AUC = 0.62). The SZ PRS predicts persistent differences in cognition and negative symptoms. The SZ PRS also predicts who among those who appear to have a mood disorder with psychosis at first admission will ultimately be diagnosed with a schizophrenia spectrum disorder. These findings show potential for the SZ PRS to become a tool for diagnosis and treatment planning.

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Schizophrenia Polygenic Risk Score and 20-Year Course of Illness in Psychotic Disorders

10.1101/581579 ◽

2019 ◽

Author(s):

Katherine G. Jonas ◽

Todd Lencz ◽

Kaiqiao Li ◽

Anil K. Malhotra ◽

Greg Perlman ◽

...

Keyword(s):

Risk Score ◽

Negative Symptoms ◽

Psychotic Disorders ◽

Illness Severity ◽

Polygenic Risk Score ◽

Course Of Illness ◽

Polygenic Risk ◽

County Mental Health ◽

Health Project ◽

First Admission

AbstractUnderstanding whether and how the schizophrenia polygenic risk score (SZ PRS) predicts course of illness could improve diagnostics and prognostication in psychotic disorders. We tested whether the SZ PRS predicts symptoms, cognition, illness severity, and diagnostic changes over the 20 years following first admission. The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Patients were assessed six times over 20 years, and 249 provided DNA. Geographically- and demographically-matched never psychotic adults were recruited at year 20, and 205 provided DNA. Symptoms were rated using the Schedule for the Assessment of Positive Symptoms and Schedule for the Assessment of Negative Symptoms. Cognition was evaluated with a comprehensive neuropsychological battery. Illness severity and diagnosis were determined by consensus of study psychiatrists. SZ PRS was significantly higher in first-admission than never psychotic groups. Within the psychosis cohort, the SZ PRS predicted more severe negative symptoms (β= 0.21), lower GAF (β= −0.28), and worse cognition (β= −0.35), across the follow-up. The SZ PRS was the strongest predictor of diagnostic shifts from affective to non-affective psychosis over the 20 years (AUC = 0.62). The SZ PRS predicts persistent differences in cognition and negative symptoms. The SZ PRS also predicts who among those who appear to have a mood disorder with psychosis at first admission will ultimately be diagnosed with a schizophrenia spectrum disorder. These findings show potential for the SZ PRS to become a powerful tool for diagnosis and treatment planning.

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Common Taxonomy of Traits and Symptoms: Linking Schizophrenia Symptoms, Schizotypy, and Normal Personality

Schizophrenia Bulletin ◽

10.1093/schbul/sbz005 ◽

2019 ◽

Vol 45 (6) ◽

pp. 1336-1348 ◽

Cited By ~ 7

Author(s):

David C Cicero ◽

Katherine G Jonas ◽

Kaiqiao Li ◽

Greg Perlman ◽

Roman Kotov

Keyword(s):

Negative Symptoms ◽

Psychotic Disorders ◽

Factor Model ◽

Symptom Dimensions ◽

Normal Personality ◽

County Mental Health ◽

Best Fitting ◽

Health Project ◽

Different Dimensions ◽

Reality Distortion

Abstract The associations among normal personality and many mental disorders are well established, but it remains unclear whether and how symptoms of schizophrenia and schizotypal traits align with the personality taxonomy. This study examined the joint factor structure of normal personality, schizotypy, and schizophrenia symptoms in people with psychotic disorders (n = 288) and never-psychotic adults (n = 257) in the Suffolk County Mental Health Project. First, we evaluated the structure of schizotypal (positive schizotypy, negative schizotypy, and mistrust) and normal traits. In both the psychotic-disorder and never-psychotic groups, the best-fitting model had 5 factors: neuroticism, extraversion, conscientiousness, agreeableness, and psychoticism. The schizotypy traits were placed on different dimensions: negative schizotypy went on (low) extraversion, whereas positive schizotypy and mistrust went on psychoticism. Next, we added symptoms to the model. Numerous alternatives were compared, and the 5-factor model remained best-fitting. Reality distortion (hallucinations and delusions) and disorganization symptoms were placed on psychoticism, and negative symptoms were placed on extraversion. Models that separated symptom dimensions from trait dimensions did not fit well, arguing that taxonomies of symptoms and traits are aligned. This is the first study to show that symptoms of psychosis, schizotypy, and normal personality reflect the same underlying dimensions. Specifically, (low) extraversion, negative schizotypy, and negative symptoms form one spectrum, whereas psychoticism, positive schizotypy, and positive and disorganized symptoms form another. This framework helps to understand the heterogeneity of psychosis and comorbidity patterns found in psychotic disorders. It also underscores the importance of traits to understanding these disorders.

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Effects of complement gene‐set polygenic risk score on brain volume and cortical measures in patients with psychotic disorders and healthy controls

American Journal of Medical Genetics Part B Neuropsychiatric Genetics ◽

10.1002/ajmg.b.32820 ◽

2020 ◽

Vol 183 (8) ◽

pp. 445-453

Author(s):

Jessica F. Holland ◽

Donna Cosgrove ◽

Laura Whitton ◽

Denise Harold ◽

Aiden Corvin ◽

...

Keyword(s):

Risk Score ◽

Psychotic Disorders ◽

Brain Volume ◽

Polygenic Risk Score ◽

Healthy Controls ◽

Polygenic Risk ◽

Gene Set ◽

Complement Gene

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Service Use and Outcomes of First-Admission Patients With Psychotic Disorders in the Suffolk County Mental Health Project

American Journal of Psychiatry ◽

10.1176/appi.ajp.162.7.1291 ◽

2005 ◽

Vol 162 (7) ◽

pp. 1291-1298 ◽

Cited By ~ 16

Author(s):

Ramin Mojtabai ◽

Daniel Herman ◽

Ezra S. Susser ◽

Nancy Sohler ◽

Thomas J. Craig ◽

...

Keyword(s):

Mental Health ◽

Service Use ◽

Psychotic Disorders ◽

Suffolk County ◽

County Mental Health ◽

Health Project ◽

First Admission

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Obstetric Complications and Polygenic Risk Score: Which Role in Predicting a Severe Short-Term Outcome in Psychosis?

Genes ◽

10.3390/genes12121895 ◽

2021 ◽

Vol 12 (12) ◽

pp. 1895

Author(s):

Sarah Tosato ◽

Chiara Bonetto ◽

Evangelos Vassos ◽

Antonio Lasalvia ◽

Katia De Santi ◽

...

Keyword(s):

Risk Score ◽

Prognostic Indicator ◽

Obstetric Complications ◽

First Episode ◽

Polygenic Risk Score ◽

Environment Interaction ◽

Short Term ◽

Term Outcome ◽

Course Of Illness ◽

Polygenic Risk

Understanding and improving the outcomes of psychosis remains a major challenge for clinical research. Obstetric complications (OCs) as a risk factor for schizophrenia (SZ) have been investigated as a potential predictor of outcomes in relation to illness severity and poorer treatment outcome, but there are less reports on first episode psychosis (FEP) patients. We test whether OCs, collected in a cohort of FEP patients, can predict illness course and psychopathology severity after 2 years from the onset. Moreover, we explore whether the SZ-polygenic risk score (PRS) would predict the illness course and whether the interaction between OCS and PRS shows a significant effect. A cohort of 264 FEP patients were assessed with standardized instruments. OCs were recorded using the Lewis–Murray scale in interviews with the patients’ mothers: 30% of them reported at least one OC. Patients with at least one OC were more likely to have a non-remitting course of illness compared to those without OCs (35.3% vs. 16.3%, p = 0.014). No association between SZ-PRS and course of illness nor evidence for a gene–environment interaction was found. In our sample, poor short-term outcomes were associated with OCs, while SZ-PRS was not a prognostic indicator of poor outcomes.

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