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Psychoneuroendocrinology. 2013 Feb;38(2):201-8. doi: 10.1016/j.psyneuen.2012.05.016. Epub 2012 Jun 18.

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

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Institute of Psychology, Leiden University, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands.



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.


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.


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.


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.

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