Modulation of stress reactivity in brain and body by serotonin transporter promoter polymorphism

Abstract

The polymorphism of the serotonin transporter gene in the promoter region (5HTTLPR) has been considered to link with vulnerability to depression and anxiety. This paper introduces a series of our studies showing that this genetic polymorphism can explain portions of individual differences in stress reactivity at multiple levels: brain functions, peripheral physiological responses, and behaviors. Specifically: (a) carriers of double short (S) alleles, compared with carriers of at least one long (L) allele, show greater activation in the hypothalamus and larger reactivity in blood catecholamine, cortisol, and an inflammatory cytokine to acute stress; (b) carriers of double S alleles are more sensitive to punishment, and thus show poorer performance in a decision-making situation where they have to stick to a long-term correct option regardless of short-term punishment; and (c) carriers of double S alleles show greater activation of the amygdala and a correlation between amygdalar activity and an increase of natural killer cell proportion in blood when positive emotions are elicited. A possible model to explain the biological mechanisms underlying those phenomena is proposed and the ecological adaptive values of the 5HTTLPR genotypes are discussed. © Japanese Psychological Association 2011.