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Mechanisms of gene–environment interactions in depression: evidence that genes potentiate multiple sources of adversity

Published online by Cambridge University Press:  06 October 2008

M. Wichers ,
D. Schrijvers ,
N. Geschwind ,
N. Jacobs ,
I. Myin-Germeys ,
E. Thiery ,
C. Derom ,
B. Sabbe ,
F. Peeters  and
Ph. Delespaul
...Show all authors
M. Wichers*
Affiliation:
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands
D. Schrijvers
Affiliation:
University of Antwerp, Collaborative Antwerp Psychiatric Research Institute (CAPRI), Antwerp, Belgium
N. Geschwind
Affiliation:
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands
N. Jacobs
Affiliation:
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands Faculty of Psychology, Open University of The Netherlands, Heerlen, The Netherlands
I. Myin-Germeys
Affiliation:
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands
E. Thiery
Affiliation:
Association for Scientific Research in Multiple Births, Ghent, Belgium
C. Derom
Affiliation:
Department of Human Genetics, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium
B. Sabbe
Affiliation:
University of Antwerp, Collaborative Antwerp Psychiatric Research Institute (CAPRI), Antwerp, Belgium
F. Peeters
Affiliation:
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands
Ph. Delespaul
Affiliation:
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands
J. van Os
Affiliation:
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands Division of Psychological Medicine, Institute of Psychiatry, London, UK
*
*Address for correspondence: Dr M. Wichers, Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University Medical Centre, Vijverdalseweg 1, Concorde Building, Maastricht, The Netherlands. (Email: [email protected])
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Abstract

Background

Previous work suggests that daily life stress-sensitivity may be an intermediary phenotype associated with both genetic risk for depression and developmental stress exposures. In the current analysis we hypothesized that genetic risk for depression and three environmental exposures over the course of development [prenatal stress, childhood adversity and adult negative life events (NLEs)] combine synergistically to produce the phenotype of stress-sensitivity.

Method

Twin pairs (n=279) participated in a momentary assessment study using the Experience Sampling Method (ESM), collecting appraisals of stress and negative affect (NA) in the flow of daily life. Prospective data on birthweight and gestational age, questionnaire data on childhood adversity and recent NLEs, and interview data on depression were used in the analyses. Daily life stress-sensitivity was modelled as the effect of ESM daily life stress appraisals on ESM NA.

Results

All three developmental stress exposures were moderated by genetic vulnerability, modelled as dizygotic (DZ) or monozygotic (MZ) co-twin depression status, in their effect on daily life stress-sensitivity. Effects were much stronger in participants with MZ co-twin depression and a little stronger in participants with DZ co-twin depression status, compared to those without co-twin depression. NLE main effects and NLE genetic moderation were reducible to birthweight and childhood adversity.

Conclusions

The findings are consistent with the hypothesis that adult daily life stress-sensitivity is the result of sensitization processes initiated by developmental stress exposures. Genes associated with depression may act by accelerating the process of stress-induced sensitization.

Keywords

Developmental stress exposureExperience Sampling Methodgene–environment interactionnegative affectsensitization
Type
Original Articles
Information
Psychological Medicine , Volume 39 , Issue 7 , July 2009 , pp. 1077 - 1086
Copyright
Copyright © 2008 Cambridge University Press

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