期刊
PSYCHOLOGICAL MEDICINE
卷 47, 期 14, 页码 2421-2437出版社
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S0033291717000915
关键词
Depression; genetics; neurodevelopment; schizophrenia
资金
- Dutch Health Research Council (ZON-MW) [10-000-1001]
- Lundbeck
- AstraZeneca
- Eli Lilly
- Janssen Cilag
- Amsterdam: Academic Psychiatric Centre of the Academic Medical Center
- Amsterdam: mental health institution: GGZ Ingeest
- Amsterdam: mental health institution: Arkin
- Amsterdam: mental health institution: Dijk en Duin
- Amsterdam: mental health institution: GGZ Rivierduinen
- Amsterdam: mental health institution: Erasmus Medical Centre
- Amsterdam: mental health institution: GGZ Noord Holland Noord
- Maastricht: Maastricht University Medical Centre
- mental health institution: GGZ Eindhoven en De Kempen
- Maastricht: mental health institution: GGZ Breburg
- Maastricht: mental health institution: GGZ Oost-Brabant
- Maastricht: mental health institution: Vincent van Gogh voor Geestelijke Gezondheid
- Maastricht: mental health institution: Mondriaan
- Maastricht: mental health institution: Zuyderland
- Maastricht: mental health institution: MetGGZ
- Maastricht: mental health institution: Riagg-Virenze Maastricht
- Maastricht: mental health institution: Universitair Centrum Sint-Jozef Kortenberg
- Maastricht: mental health institution: CAPRI University of Antwerp
- Maastricht: mental health institution: PC Ziekeren Sint-Truiden
- Maastricht: mental health institution: PZ Sancta Maria Sint-Truiden
- Maastricht: mental health institution: GGZ Overpelt
- Maastricht: mental health institution: OPZ Rekem
- Groningen: University Medical Center Groningen
- Groningen: mental health institution: Lentis
- Groningen: mental health institution: GGZ Friesland
- Groningen: mental health institution: GGZ Drenthe
- Groningen: mental health institution: Dimence
- Groningen: mental health institution: Mediant
- Groningen: mental health institution: GGNet Warnsveld
- Groningen: mental health institution: Yulius Dordrecht
- Groningen: mental health institution: Parnassia psycho-medical center The Hague
- Utrecht: University Medical Center Utrecht
- Utrecht: mental health institution Altrecht
- Utrecht: mental health institution GGZ Centraal
- Utrecht: mental health institution Riagg Amersfoort
- Utrecht: mental health institution Delta
- European Community [HEALTH-F2-2009-241909]
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.
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