The effect of tryptophan on the cortisol response to social stress is modulated by the 5-HTTLPR genotype

OBJECTIVE The S'/S' (S/S, S/Lg and Lg/Lg) variant of the serotonin (5-HT) transporter gene linked polymorphic region (5-HTTLPR) is associated with less efficient neurotransmission and may be more reactive to 5-HT manipulations. We tested the effects of l-tryptophan supplements on the cortisol response induced by a social stressor in S'/S' and L'/L' (La/La) carriers. METHODS In a double-blind parallel design, 25 S'/S' carriers and 21 L'/L' carriers were randomised to take l-tryptophan (2.8g/d) or placebo supplements for six days. At day 7 participants were exposed to the Trier Social Stress Test. Salivary cortisol and subjective mood states were monitored before, during and after the stress procedure. RESULTS S'/S' carriers who took l-tryptophan supplements had a significantly lower cortisol response to stress than S'/S' carriers who took placebo. Tryptophan had no effect on cortisol in L'/L' carriers and no effect on subjective mood states in either genotype group. CONCLUSION Tryptophan attenuates the cortisol response to acute social stress depending on 5-HTTLPR genotype. S'/S' carriers may indeed be more reactive to 5-HT manipulations.