Appraisals of stressful life events as a genetically-linked mechanism in the stress-depression relationship

Variation in the promoter region of the serotonin transporter gene (5-HTTLPR) has been linked to various cognitive-affective indices of stress sensitivity hypothesized to underlie vulnerability to depression. The current study examined the association of 5-HTTLPR with appraisals of naturally occurring acute life stressors in a community sample of 384 youth at elevated risk for depression due to oversampling for maternal depression. Interview measures administered at youth age 20 were used to assess subjective and objective (assigned by an independent rating team) appraisals of the negative impact of recent acute stressful life events. The presence of at least one S allele was associated with elevated subjective appraisals of the negative impact of acute stressors (P = 0.03). Consistent with an endophenotype perspective, support was found for a 5-HTTLPR-stress appraisals-depression mediation model both concurrently and longitudinally. Results indicate that enhanced stress sensitivity may act as an intermediate phenotype through which 5-HTTLPR affects risk for depression. © Springer Science+Business Media, LLC 2011.