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.