Menopausal status could modulate the association between 5-HTTLPR and antidepressant efficacy in depressed women: a pilot study

The aim of this study was to evaluate the association between the functional polymorphic region of the serotonin transporter gene (5-HTTLPR) and antidepressant efficacy in menopausal and non-menopausal women. Since serotonergic system has been shown to be linked to estrogens, menopausal status of women may explain previous contradictory results on antidepressant efficacy in major depressive episode related to 5-HTTLPR in women. Seventy-four women (43 non-menopausal and 31 menopausal) and 29 men with a major depressive episode were genotyped for the 5-HTTLPR and assessed prospectively for antidepressant efficacy after 4 weeks of treatment. Non-menopausal women with at least one copy of the long allele had better antidepressant efficacy than those who were homozygous for the short allele, whereas no difference was found in menopausal women. Furthermore, antidepressant response was correlated with an interaction between the 5-HTTLPR polymorphism and age in women, but not in men. This finding suggested that the differences in antidepressant response were not linked to age but, rather, to menopausal status of women. Further research on a bigger sample is needed with steroids measurements to determine how menopausal status and 5-HTTLPR polymorphism influence antidepressant response.