Serotonin transporter availability may moderate the association between perceiving stress and depressive tendencies — A SPECT with 5-HTTLPR genotyping study

• Whether serotonergic activity is related to stress on depression is unclear.
• We probed this interaction in a SPECT study with [123I]ADAM.
• SERT availability was found to moderate the link between stress and depression.
• Males with low SERT availability could be vulnerable to stress-induced depression.

It was found that serotonin transporter (SERT) gene (5-HTTLPR) polymorphism may moderate the association between perceiving stress and depressive tendency. Although SERT availability in the central nervous system could be associated with 5-HTTLPR polymorphism, whether SERT availability moderates the association between stress and depressive tendency is unclear. This study aimed to investigate whether there is a SERT availability × environmental stress interaction effect, as well as a gene-by-environmental (G × E) interaction effect, using single-photon emission computed tomography (SPECT) with a serotonin transporter radiotracer, [123I]ADAM. 87 healthy volunteers were enrolled. The SERT availability was approximated using SPECT with [123I]ADAM. Stress and depressive tendencies were measured by the Recent Life Change Questionnaire (RLCQ) and the Taiwanese Depression Questionnaire (TDQ), respectively. A significant interaction of sex × RLCQ × thalamic SERT availability on the TDQ was found, and this effect was robust after controlling for the effect of the SS genotype. The interaction of RLCQ × thalamic SERT availability on the TDQ was significant among males. In particular, a significant association between RLCQ and TDQ (Spearman correlation, ρ = 0.64, p < 0.01) was found among male subjects with a lower level of thalamic SERT availability. SERT availability may play a role in depressive tendency when under perceived stress among healthy individuals, independent of G × E. This finding provides new evidence that confirms the role of the serotonergic system in the association between stress and depression. Males with lower levels of SERT availability may be more vulnerable to the effects of negative life events.