Serotonin transporter polymorphism predicts waking cortisol in young girls

Michael C. Chen, Jutta Joormann, Joachim Hallmayer, Ian H. Gotlib

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Major Depressive Disorder (MDD) is one of the most prevalent and costly of all psychiatric disorders. The hypothalamic pituitary adrenal (HPA)-axis, which regulates the hormonal response to stress, has been found to be disrupted in depression. HPA dysregulation may represent an important risk factor for depression. To examine a possible genetic underpinning of this risk factor without the confound of current or lifetime depression, we genotyped 84 never-disordered young girls, over a third of whom were at elevated risk for depression, to assess the association between a polymorphism in the promoter region of the serotonin transporter (5-HTT) gene and diurnal variation in HPA-axis activity. This 5-HTT-linked polymorphic region (5-HTTLPR) has been previously found to interact with stress to increase risk for depression. We found 5-HTTLPR to be significantly associated with diurnal cortisol levels: girls who were homozygous for the short-allele had higher levels of waking (but not afternoon or evening) cortisol than did their long-allele counterparts. This finding suggests that genetic susceptibility to HPA-axis dysregulation, especially apparent in levels of waking cortisol, is detectable in individuals as young as 9 years of age.

Original languageEnglish (US)
Pages (from-to)681-686
Number of pages6
Issue number5
StatePublished - Jun 2009
Externally publishedYes


  • 5-HTTLPR
  • Depression
  • Diurnal cortisol
  • HPA-axis
  • Serotonin transporter
  • Stress

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Endocrine and Autonomic Systems


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