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 language | English |
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Pages (from-to) | 2421-2437 |
Number of pages | 17 |
Journal | Psychological Medicine |
Volume | 47 |
Issue number | 14 |
DOIs | |
Publication status | Published - Oct 2017 |
Keywords
- Depression
- genetics
- neurodevelopment
- schizophrenia
- GENETIC RISK
- GENERAL-POPULATION
- NEGATIVE SYMPTOMS
- CHILDHOOD TRAUMA
- COGNITIVE IMPAIRMENT
- STRUCTURED INTERVIEW
- MENTAL-DISORDERS
- SCHIZOPHRENIA
- DEPRESSION
- RELIABILITY