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Evidence that polygenic risk for psychotic disorder is expressed in the domain of neurodevelopment, emotion regulation and attribution of salience

Published online by Cambridge University Press:  24 April 2017

J. van Os ,
Y. van der Steen ,
Md. A. Islam ,
S. Gülöksüz ,
B. P. Rutten ,
C. J. Simons  and
GROUP Investigators
J. van Os*
Affiliation:
Department of Psychiatry and Psychology, Maastricht University Medical Centre, Maastricht, The Netherlands Department of Psychosis Studies, King's College London, King's Health Partners, Institute of Psychiatry, London, UK
Y. van der Steen
Affiliation:
Department of Psychiatry and Psychology, Maastricht University Medical Centre, Maastricht, The Netherlands
Md. A. Islam
Affiliation:
University of Groningen, University Medical Center Groningen, University Center for Psychiatry, Groningen, The Netherlands
S. Gülöksüz
Affiliation:
Department of Psychiatry and Psychology, Maastricht University Medical Centre, Maastricht, The Netherlands
B. P. Rutten
Affiliation:
Department of Psychiatry and Psychology, Maastricht University Medical Centre, Maastricht, The Netherlands
C. J. Simons
Affiliation:
Department of Psychiatry and Psychology, Maastricht University Medical Centre, Maastricht, The Netherlands GGzE, Institute for Mental Health Care Eindhoven and De Kempen, Eindhoven, The Netherlands
*
*Address for correspondence: J. van Os, Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Centre Utrecht, Heidelberglaan 100, Utrecht, the Netherlands. (Email: [email protected])
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Abstract

Background

The liability-threshold model of psychosis risk predicts stronger phenotypic manifestation of the polygenic risk score (PRS) in the healthy relatives of patients, as compared with healthy comparison subjects.

Methods

First-degree relatives of patients with psychotic disorder (871 siblings and 812 parents) and healthy comparison subjects (n = 523) were interviewed three times in 6 years. Repeated measures of two psychosis phenotypes, the Community Assessment of Psychic Experiences (CAPE; self-report – subscales of positive, negative and depressive symptoms) and the Structured Interview for Schizotypy – Revised (SIS-R; clinical interview – subscales of positive and negative schizotypy), were examined for association with PRS. Interview-based lifetime rate of depressive and manic episodes were also examined, as was association with repeated measures of intelligence quotient (IQ).

Results

In the relatives, PRS was associated with CAPE/SIS-R total score (respectively, B = 0.12, 95% CI 0.02–0.22 and B = 0.11, 95% CI 0.02–0.20), the SIS-R positive subscale (B = 0.16, 95% CI 0.04–0.28), the CAPE depression subscale (B = 0.21, 95% CI 0.07–0.34), any lifetime affective episode (OR 3.1, 95% CI 1.04–9.3), but not with IQ (B = −1.8, 95% CI −8.0 to 4.4). In the controls, similar associations were apparent between PRS on the one hand and SIS-R total score, SIS-R positive, SIS-R negative, any lifetime affective episode and, in contrast, lower IQ (B = −8.5, 95% CI −15.5 to −1.6).

Conclusions

In non-ill people, polygenic risk for psychotic disorder is expressed pleiotropically in the domain of neurodevelopment, emotion regulation and attribution of salience. In subjects at elevated genetic risk, emerging expression of neurodevelopmental alterations may create floor effects, obscuring genetic associations.

Keywords

Depressiongeneticsneurodevelopmentschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 47 , Issue 14 , October 2017 , pp. 2421 - 2437
Copyright
Copyright © Cambridge University Press 2017 

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Footnotes

†

See Appendix.

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