Abstract
BACKGROUND: The short (s) allele of the serotonin transporter gene promoter (5-HTTLPR) may be associated with exposure to social adversities and the subsequent onset of depressive illness in adulthood. AIMS: To test in adolescents at high risk for depression whether the short 's' allele is associated with levels of morning cortisol and the subsequent onset of a depressive episode. METHOD: High-risk adolescents (n = 403) were genotyped for 5-HTTLPR. Salivary samples were obtained on four consecutive school days within 1 h of waking from 393 (97.5%) individuals and 367 (91%) underwent a mental state reassessment at 12 months. RESULTS: Multilevel analysis revealed higher levels of salivary cortisol in short allele carriers (s/s>s/l>l/l). A subsequent episode of depression was increased in those with higher cortisol and the 's' allele, and independently by depressive symptoms at entry, in both genders. CONCLUSIONS: The short allele of 5-HTTLPR may moderate the association between morning cortisol and the subsequent onset of a depressive episode.