Serotonin transporter genotype, morning cortisol and subsequent depression in adolescents

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.