Schizophrenia Polygenic Risk Score as a Predictor of Antipsychotic Efficacy in First-Episode Psychosis

AbstractDiagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03–0.33) and positive (B = 0.19; 95%CI 0.03–0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11–0.52) and in controls (B = 0.26; 95%CI 0.06–0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders.

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Polygenic Risk Score associated with specific symptom dimensions in first-episode psychosis

Schizophrenia Research ◽

10.1016/j.schres.2016.11.039 ◽

2017 ◽

Vol 184 ◽

pp. 116-121 ◽

Cited By ~ 19

Author(s):

Sarojini M. Sengupta ◽

Kathleen MacDonald ◽

Ferid Fathalli ◽

Anita Yim ◽

Martin Lepage ◽

...

Keyword(s):

Risk Score ◽

First Episode Psychosis ◽

First Episode ◽

Polygenic Risk Score ◽

Specific Symptom ◽

Symptom Dimensions ◽

Polygenic Risk ◽

Episode Psychosis

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S125. THE ROLE OF DUP, DUI AND POLYGENIC SCORE FOR SCHIZOPHRENIA ON COGNITION IN ATHENS FEP STUDY SAMPLE

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa031.191 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S82-S83

Author(s):

Stefanos Dimitrakopoulos ◽

Alex Hatzimanolis ◽

Pentagiotissa Stefanatou ◽

Lida-Alkisti Xenaki ◽

Nikos Stefanis

Keyword(s):

Risk Score ◽

Cognitive Deficit ◽

Assessment Tool ◽

First Episode Psychosis ◽

First Episode ◽

P Value ◽

Polygenic Risk Score ◽

Inform Consent ◽

Polygenic Risk ◽

Episode Psychosis

Abstract Background It remains unclear which biological mechanisms affect neurocognition in first episode psychosis (FEP) patients. There is minimal evidence from current literature suggesting an association between duration of untreated psychosis (DUP) or duration of untreated illness (DUI) and cognitive decline in FEP patients. It is still controversial whether genetic factors, such as polygenic risk score for schizophrenia, determine observed cognitive deficits. The study of interplay between DUP, DUI and genetic risk factors might be important to understand underlying pathways. Methods Ninety FEP patients where recruited during Athens First-Episode Psychosis Research study between 2015–2018. All participants provided inform consent. DUP for each patient was defined by NOS-DUP (Nottingham onset schedule: modified DUP version) assessment tool and DUI was determined using the symptom onset in schizophrenia (SOS) inventory. DNA was collected in order to create polygenic risk score (PGC) for schizophrenia for each individual using SNPs selected according to the significance of their association with the phenotype at nominal p-value thresholds of 0,05. WAIS-IV total score and subscales, i.e. Verbal Comprehension (VC), Perceptual Reasoning (PR), Working Memory (WM), Processing Speed (PS) and moreover index differences between these 4 subscales were applied as a measure of cognitive deficit. Results Generalized linear model analysis, after adjustment for years of education and gender, found no significant main effect of DUP, DUI or PGC on any cognitive subscale. Furthermore, conducting an exploratory analysis for possible interactions between DUP/DUI and PGC (n=90), we found statistically significant findings of DUP x PGC (F=8,175, p=,005) and DUI x PGC (F=5,592, p=,021) for the cognitive variable of VC/WM difference. The interplay between DUP and PCG and DUI and PGC was associated with observed differences between VM and WM in our FEP sample. Discussion Our preliminary results are consistent with recent literature suggesting that neurocognition is not determined by DUP, DUI or PGC for schizophrenia. Novel approach based on WAIS-IV indexes of interest allows to explore subtle differences between cognitive subdomains. Elucidating underlying interplay between genetic and disease-related mechanisms could be important to understand the core feature of cognitive deficit in FEP patients.

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Schizophrenia polygenic risk score and cannabis use modify psychosis expression in first episode psychosis patients and population controls

10.1101/19013284 ◽

2019 ◽

Author(s):

Diego Quattrone ◽

Ulrich Reininghaus ◽

Alex L. Richards ◽

Giada Tripoli ◽

Laura Ferraro ◽

...

Keyword(s):

Continuous Distribution ◽

First Episode Psychosis ◽

Cannabis Use ◽

Psychotic Symptoms ◽

First Episode ◽

Polygenic Risk Score ◽

Small Magnitude ◽

Polygenic Risk ◽

Episode Psychosis ◽

Population Controls

AbstractBackgroundDiagnostic categories within the psychosis spectrum are widely used in clinical practice, however psychosis may occur on a continuum. Therefore, we explored whether the continuous distribution of psychotic symptoms across categories is a function of genetic as well as environmental risk factors, such as polygenic risk scores (PRSs) and cannabis use.MethodsAs part of the EU-GEI study, we genotyped first episode psychosis patients (FEP) and population controls, for whom transdiagnostic dimensions of psychotic symptoms or experiences were generated using item response bi-factor modelling. Linear regression was used, separately in patients and controls, to test the associations between these dimensions and schizophrenia (SZ) PRSs, as well as the combined effect of SZ-PRS and cannabis use on the positive symptom/experience dimensions.ResultsSZ-PRS was associated with negative (B=0.18; 95%CI 0.03 to 0.34) and positive (B=0.19; 95%CI 0.03 to 0.36) symptom dimensions in 617 FEP, and with all the psychotic experience dimensions in 979 controls. The putative effect of SZ-PRS on either symptom or experience dimensions was of a small magnitude. Cannabis use was additionally associated with the positive dimensions both in FEP (B=0.31; 95%CI 0.11 to 0.52) and in controls (B=0.26; 95%CI 0.06 to 0.46), independently from SZ-PRS.ConclusionsWe report two validators to the latent dimensional structure of psychosis. SZ risk variants and cannabis use independently map onto specific dimensions, contributing to variation across the psychosis continuum. Findings support the hypothesis that psychotic experiences have similar biological substrates as clinical disorders.

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Letter to the editor: Is polygenic risk for Parkinson's disease associated with less risk of first episode psychosis?

Psychological Medicine ◽

10.1017/s0033291719002435 ◽

2019 ◽

Vol 50 (1) ◽

pp. 173-176

Author(s):

Diego Quattrone ◽

Alex Richards ◽

Ulrich Reininghaus ◽

Evangelos Vassos ◽

Michael O'Donovan ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

First Episode Psychosis ◽

First Episode ◽

Polygenic Risk ◽

Letter To The Editor ◽

Episode Psychosis

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POLYGENIC RISK SCORE ANALYSES OF SYMPTOMS AND TREATMENT RESPONSE IN A FIRST EPISODE SCHIZOPHRENIA COHORT

European Neuropsychopharmacology ◽

10.1016/j.euroneuro.2017.08.159 ◽

2019 ◽

Vol 29 ◽

pp. S869

Author(s):

Marcos Santoro ◽

Vanessa Ota ◽

Simone de Jong ◽

Cristiano Noto ◽

Fernanda Talarico ◽

...

Keyword(s):

Treatment Response ◽

Risk Score ◽

First Episode ◽

Polygenic Risk Score ◽

Polygenic Risk ◽

First Episode Schizophrenia

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Jumping to conclusions, general intelligence, and psychosis liability: findings from the multi-centre EU-GEI case-control study

Psychological Medicine ◽

10.1017/s003329171900357x ◽

2020 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Giada Tripoli ◽

Diego Quattrone ◽

Laura Ferraro ◽

Charlotte Gayer-Anderson ◽

Victoria Rodriguez ◽

...

Keyword(s):

Cognitive Biases ◽

Population Based ◽

Case Control ◽

Risk Scores ◽

First Episode ◽

Polygenic Risk Score ◽

General Intelligence ◽

Polygenic Risk ◽

Jumping To Conclusions ◽

Episode Psychosis

Abstract Background The ‘jumping to conclusions’ (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ. Methods A total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia. Results The estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI −0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25–0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B = −1.7, 95% CI −2.8 to −0.5, p = 0.006), but did not relate to delusions in patients. Conclusions Our findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis.

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