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


METHODS
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.
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands. m.wichers@sp.unimaas.nl
M
M
Wichers
D
D
Schrijvers
N
N
Geschwind
N
N
Jacobs
I
I
Myin-Germeys
E
E
Thiery
C
C
Derom
B
B
Sabbe
F
F
Peeters
Ph
P
Delespaul
J
J
van Os
D000293:Adolescent; D000328:Adult; D001530:Belgium; D001724:Birth Weight; D003865:Major Depressive Disorder / Q000235:genetics* / Q000523:psychology; D004200:Diseases in Twins / Q000235:genetics* / Q000523:psychology; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006306:Health Surveys; D006801:Humans; D008016:Life Change Events; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D012931:Social Environment; D014429:Twins, Dizygotic / Q000235:genetics / Q000523:psychology; D014430:Twins, Monozygotic / Q000235:genetics / Q000523:psychology; D055815:Young Adult