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

J. van Os*, Y. van der Steen, Md. A. Islam, S. Guluksuz, B. P. Rutten, C. J. Simons, Genetic Risk and Outcome of Psychosis (GROUP) Investigators

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

43 Citations (Web of Science)

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 neuro-development, emotion regulation and attribution of salience. In subjects at elevated genetic risk, emerging expression of neurodevelopmental alterations may create floor effects, obscuring genetic associations.

Original languageEnglish
Pages (from-to)2421-2437
Number of pages17
JournalPsychological Medicine
Volume47
Issue number14
DOIs
Publication statusPublished - Oct 2017

Keywords

  • Depression
  • genetics
  • neurodevelopment
  • schizophrenia
  • GENETIC RISK
  • GENERAL-POPULATION
  • NEGATIVE SYMPTOMS
  • CHILDHOOD TRAUMA
  • COGNITIVE IMPAIRMENT
  • STRUCTURED INTERVIEW
  • MENTAL-DISORDERS
  • SCHIZOPHRENIA
  • DEPRESSION
  • RELIABILITY

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