Interaction between genetic polymorphisms and stressful life events in first episode depression.

BACKGROUND: A polymorphism in the serotonin transporter (5-HTT) gene seems to moderate the influence of stressful life events on depression. However, the results from previous studies of gene-environment interactions in depression are inconsistent and might be confounded by the history of depression among participants.

METHOD: We applied a case-only design, including 290 ethnically homogeneous patients suffering exclusively from first episode depression. Psychiatric mo-morbidity, personality traits and disorders and stressful life events in a six months period preceding onset of depression were evaluated by means of interviews and questionnaires. Additionally, we genotyped nine polymorphisms in the genes encoding the serotonin transporter, brain derived neurotrophic factor, catechol-O-methyltransferase, angiotensin converting enzyme, tryptophane hydroxylase, and the serotonin receptors 1A, 2A, and 2C.

RESULTS: The low activity variants of the 5-HTT-linked polymorphic region in the serotonin transporter gene and the Met-allele of a single nucleotide polymorphism (Val66Met) in the gene encoding brain derived neurotrophic factor were independently associated with the presence of stressful life events prior to onset of depression, also when corrected for the effect of age, gender, marital status, personality disorder, neuroticism, and severity of depressive symptoms at the time of interview.

CONCLUSION: Polymorphisms in the genes encoding the serotonin transporter and the brain derived neurotrophic factor interact with recent stressful life events on depression among patients with no history of previous depressive episodes.