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Evidence that polygenic risk for psychotic disorder is expressed in the domain of neurodevelopment, emotion regulation and attribution of salience.
Psychol Med. 2017 Oct; 47(14):2421-2437.PM

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.

Authors+Show Affiliations

Department of Psychiatry and Psychology,Maastricht University Medical Centre,Maastricht,The Netherlands.Department of Psychiatry and Psychology,Maastricht University Medical Centre,Maastricht,The Netherlands.University of Groningen, University Medical Center Groningen, University Center for Psychiatry,Groningen,The Netherlands.Department of Psychiatry and Psychology,Maastricht University Medical Centre,Maastricht,The Netherlands.Department of Psychiatry and Psychology,Maastricht University Medical Centre,Maastricht,The Netherlands.Department of Psychiatry and Psychology,Maastricht University Medical Centre,Maastricht,The Netherlands.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28436345

Citation

van Os, J, et al. "Evidence That Polygenic Risk for Psychotic Disorder Is Expressed in the Domain of Neurodevelopment, Emotion Regulation and Attribution of Salience." Psychological Medicine, vol. 47, no. 14, 2017, pp. 2421-2437.
van Os J, van der Steen Y, Islam MA, et al. Evidence that polygenic risk for psychotic disorder is expressed in the domain of neurodevelopment, emotion regulation and attribution of salience. Psychol Med. 2017;47(14):2421-2437.
van Os, J., van der Steen, Y., Islam, M. A., Gülöksüz, S., Rutten, B. P., & Simons, C. J. (2017). Evidence that polygenic risk for psychotic disorder is expressed in the domain of neurodevelopment, emotion regulation and attribution of salience. Psychological Medicine, 47(14), 2421-2437. https://doi.org/10.1017/S0033291717000915
van Os J, et al. Evidence That Polygenic Risk for Psychotic Disorder Is Expressed in the Domain of Neurodevelopment, Emotion Regulation and Attribution of Salience. Psychol Med. 2017;47(14):2421-2437. PubMed PMID: 28436345.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence that polygenic risk for psychotic disorder is expressed in the domain of neurodevelopment, emotion regulation and attribution of salience. AU - van Os,J, AU - van der Steen,Y, AU - Islam,Md A, AU - Gülöksüz,S, AU - Rutten,B P, AU - Simons,C J, AU - ,, Y1 - 2017/04/24/ PY - 2017/4/25/pubmed PY - 2018/5/29/medline PY - 2017/4/25/entrez KW - Depression KW - genetics KW - neurodevelopment KW - schizophrenia SP - 2421 EP - 2437 JF - Psychological medicine JO - Psychol Med VL - 47 IS - 14 N2 - 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. SN - 1469-8978 UR - https://www.unboundmedicine.com/medline/citation/28436345/Evidence_that_polygenic_risk_for_psychotic_disorder_is_expressed_in_the_domain_of_neurodevelopment_emotion_regulation_and_attribution_of_salience_ L2 - https://www.cambridge.org/core/product/identifier/S0033291717000915/type/journal_article DB - PRIME DP - Unbound Medicine ER -