Differing Models of Association between Childhood Events, Recent Life Stressors, Psychological Resilience and Depression across Three Alleles of the Serotonin Transporter 5-HTTLPR

Abstract

Background: Although some previous research has implicated the short form (ss) of the serotonin transporter 5-HTTLPR gene in the association between distal and proximal environmental stress and depression, over 38% of studies included in a recent meta-analysis failed to support that finding. Another variant of the 5-HTTLPT, the sl, has been relatively under-examined and may explain the inconsistency of the ss/ll dichotomy. In addition, a potential 'buffer' variable between proximal and distal stress and depression - psychological resilience - may interact with the forms of the 5-HTTLPR. This study investigated the ways the three forms of the 5-HTTLPR interacted with distal and proximal stress, and psychological resilience, to predict depression. Methods: A volunteer community sample of 65 female and 55 male volunteers completed background, childhood stress (Adverse Childhood Events-ACE), recent stress (RLS), depression (Zung Self-Rating Depression Scale-ZSDS) and resilience (Connors-Davidson Resilience Scale-CD-RISC) questionnaires, plus gave a sample for genotyping to determine presence of ss, sl, or ll variants of the 5-HTTLPR. Results: Comparison of the regression equations for each 5-HTTLPR variant showed that the combination of ACE, RLS and CD-RISC significantly predicted ZSDS scores for the sl variant; ACE, CD-RISC (but not RLS) significantly predicted ZSDS for the ll variant; and none of these significantly predicted ZSDS for the ss variant. Conclusions: Previous inconsistent findings regarding the differences in the stress-depression interaction for the ss and ll may be explained by the more complex interaction effects of the sl variant with distal and recent stressors and psychological resilience.