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

Published on Mar 18, 2019in bioRxiv
· DOI :10.1101/581579
Katherine Grace Jonas (SUNY: State University of New York System), Katherine Grace Jonas (SUNY: State University of New York System)+ 5 AuthorsRoman Kotov36
Estimated H-index: 36
(SBU: Stony Brook University)
Abstract Understanding 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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Published on Jan 4, 2019in Molecular Psychiatry 11.97
Valentina Escott-Price28
Estimated H-index: 28
(Cardiff University),
Matthew Bracher-Smith1
Estimated H-index: 1
(Cardiff University)
+ 4 AuthorsMichael C. O’Donovan120
Estimated H-index: 120
(Cardiff University)
Published on Jan 1, 2019in American Journal of Psychiatry 13.65
Jian-Ping Zhang11
Estimated H-index: 11
Delbert Robinson39
Estimated H-index: 39
+ 8 AuthorsAnil K. Malhotra57
Estimated H-index: 57
Objective:Pharmacogenomic studies of antipsychotics have typically examined effects of individual polymorphisms. By contrast, polygenic risk scores (PRSs) derived from genome-wide association studies (GWAS) can quantify the influence of thousands of common alleles of small effect in a single measure. The authors examined whether PRSs for schizophrenia were predictive of antipsychotic efficacy in four independent cohorts of patients with first-episode psychosis (total N=510).Method:All study subj...
Published on Dec 1, 2018in Translational Psychiatry 5.18
Rebecca Shafee9
Estimated H-index: 9
(Broad Institute),
Pranav Nanda6
Estimated H-index: 6
(Columbia University)
+ 16 AuthorsScot K. Hill4
Estimated H-index: 4
(RFUMS: Rosalind Franklin University of Medicine and Science)
Psychotic disorders including schizophrenia are commonly accompanied by cognitive deficits. Recent studies have reported negative genetic correlations between schizophrenia and indicators of cognitive ability such as general intelligence and processing speed. Here we compare the effect of polygenetic risk for schizophrenia (PRSSCZ) on measures that differ in their relationships with psychosis onset: a measure of current cognitive abilities (the Brief Assessment of Cognition in Schizophrenia, BAC...
Published on Sep 1, 2018in Nature Genetics 25.45
Amit Khera50
Estimated H-index: 50
Mark Chaffin10
Estimated H-index: 10
(Broad Institute)
+ 8 AuthorsPatrick T. Ellinor71
Estimated H-index: 71
(Broad Institute)
A key public health need is to identify individuals at high risk for a given disease to enable enhanced screening or preventive therapies. Because most common diseases have a genetic component, one important approach is to stratify individuals based on inherited DNA variation1. Proposed clinical applications have largely focused on finding carriers of rare monogenic mutations at several-fold increased risk. Although most disease risk is polygenic in nature2–5, it has not yet been possible to use...
Published on Aug 1, 2018in JAMA Psychiatry 15.92
Nicoline Hemager3
Estimated H-index: 3
Kerstin Jessica Plessen4
Estimated H-index: 4
(UNIL: University of Lausanne)
+ 13 AuthorsAja Neergaard Greve5
Estimated H-index: 5
Importance Children at familial high risk of schizophrenia spectrum disorders (FHR-SZ) or bipolar disorder (FHR-BP) exhibit neurocognitive impairments. Large studies of neurocognition in young children at familial high risk at the same age are important to differentiate the pathophysiology and developmental trajectory of these 2 groups. Objective To characterize neurocognitive functions in 7-year-old children with FHR-SZ or FHR-BP and a control population. Design, Setting, and Participants This ...
Published on Jan 1, 2018in JAMA Psychiatry 15.92
Judith Allardyce16
Estimated H-index: 16
(Medical Research Council),
Ganna Leonenko9
Estimated H-index: 9
(Medical Research Council)
+ 16 AuthorsArianna Di Florio9
Estimated H-index: 9
(Medical Research Council)
Importance Bipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. Alternative approaches to patient stratification beyond current diagnostic categories are needed to understand the underlying disease processes/mechanisms. Objectives To investigate the relationship between common-variant liability for schizophrenia, indexed by polygenic risk scores (PRS) and psychotic presentations of BD, using clinical descriptions which consider both occurrence and leve...
Published on Jan 1, 2018in JAMA Psychiatry 15.92
Fadila Serdarevic3
Estimated H-index: 3
(EUR: Erasmus University Rotterdam),
Philip R. Jansen9
Estimated H-index: 9
(VU: VU University Amsterdam)
+ 4 AuthorsHenning Tiemeier76
Estimated H-index: 76
(EUR: Erasmus University Rotterdam)
Published on Nov 1, 2017in American Journal of Psychiatry 13.65
Eva Veithorst22
Estimated H-index: 22
Anne-Kathrin Fett14
Estimated H-index: 14
+ 4 AuthorsRoman Kotov2
Estimated H-index: 2
(ISMMS: Icahn School of Medicine at Mount Sinai)
Objective:Social impairment is a long-recognized core feature of schizophrenia and is common in other psychotic disorders. Still, to date the long-term trajectories of social impairment in psychotic disorders have rarely been studied systematically.Methods:Data came from the Suffolk County Mental Health Project, a 20-year prospective study of first-admission patients with psychotic disorders. A never-psychotic comparison group was also assessed. Latent class growth analysis was applied to longit...
Published on Nov 1, 2017in American Journal of Psychiatry 13.65
Roman Kotov36
Estimated H-index: 36
Laura J. Fochtmann15
Estimated H-index: 15
+ 8 AuthorsGabrielle A. Carlson58
Estimated H-index: 58
Objective:Kraepelin considered declining course a hallmark of schizophrenia, but others have suggested that outcomes usually stabilize or improve after treatment initiation. The authors investigated this question in an epidemiologically defined cohort with psychotic disorders followed for 20 years after first hospitalization.Method:The Suffolk County Mental Health Project recruited first-admission patients with psychosis from all inpatient units of Suffolk County, New York (response rate, 72%). ...
Published on Oct 1, 2017in World Psychiatry 34.02
M. Owen141
Estimated H-index: 141
(Medical Research Council),
Michael C. O’Donovan120
Estimated H-index: 120
(Medical Research Council)
The idea that disturbances occurring early in brain development contribute to the pathogenesis of schizophrenia, often referred to as the neurodevelopmental hypothesis, has become widely accepted. Despite this, the disorder is viewed as being distinct nosologically, and by implication pathophysiologically and clinically, from syndromes such as autism spectrum disorders, attention-deficit/hyperactivity disorder (ADHD) and intellectual disability, which typically present in childhood and are group...
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