Stress-related negative affectivity and genetically altered serotonin transporter function: evidence of synergism in shaping risk of depression.
BACKGROUND
Genetic moderation of the depression-inducing effects of stressful life events (SLEs) has been reported, but findings suggest that genes may not moderate the effects of SLEs per se but instead may moderate the risk of depression associated with the stable tendency to develop negative emotions in response to minor environmental experiences.


OBJECTIVE
To examine whether a functional polymorphism of the serotonin transporter gene (5-HTTLPR) moderates the association between negative affectivity (neuroticism) and depression and to what degree this can explain previous findings involving SLEs.


METHODS
A prospective cohort study involving 1 baseline and 4 follow-up measurements in 15 months analyzing change in self-reported depressive symptoms across time as a function of negatively attributed SLEs, neuroticism, 5-HTTLPR, and their interactions.


METHODS
General community.


METHODS
A population-based sample of 374 ethnically homogeneous young adult female twins.


METHODS
A continuous score of self-reported depressive symptoms.


RESULTS
The depressogenic effect of SLEs in the 3 months before interview was significantly greater in women with 2 short (S) alleles compared with women with 1 or none. However, this effect disappeared after accounting for the effect of SLEs conditional on neuroticism. Similarly, the depressogenic effect of neuroticism was progressively greater with number of S alleles, and this was unchanged after accounting for the effect of neuroticism conditional on SLEs.


CONCLUSIONS
Genotype x environment interactions in depression may be more productively interpreted by involving mechanisms more proximal to psychological experience itself. The probability that stress-related cognitive vulnerabilities for depression result in symptom formation may be moderated by a neurobiologic phenotype characterized by altered processing of negative emotions associated with variation in 5-HTTLPR.
Jacobs
Nele
N
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, 6200 MD Maastricht, the Netherlands.
Kenis
Gunter
G
Peeters
Frenk
F
Derom
Catherine
C
Vlietinck
Robert
R
van Os
Jim
J
D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D003866:Depressive Disorder / Q000175:diagnosis / Q000235:genetics*; D004200:Diseases in Twins / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008016:Life Change Events; D008137:Longitudinal Studies; D008875:Middle Aged; D008957:Models, Genetic; D010551:Personality / Q000235:genetics*; D010555:Personality Inventory; D011446:Prospective Studies; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012737:Sex Factors; D013315:Stress, Psychological / Q000235:genetics / Q000523:psychology; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins