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Across multiple mental health-related measures, a polymorphism (5-HTTLPR) within the promoter of the serotonin transporter gene has been associated with differential psychological sensitivity to stressful experiences. Yet, the specific mechanisms by which this polymorphism contributes to risk for psychological dysfunction is unclear. Therefore, we investigated cortisol reactivity to psychosocial stress as a potential intermediate phenotype that might predispose to such risk.

A psychologically healthy sample of 182 young adults were genotyped for the 5-HTTLPR. Each participant delivered a speech and performed mental arithmetic in one of three audience conditions: a critical evaluative audience, a supportive evaluative audience, or no audience. Salivary cortisol was sampled at baseline and at 20, 40, and 75 min after stressor onset.

The two evaluative audience conditions …