Season and gender modify in-vivo serotonin transporter binding in depressed patients and healthy controls

Abstract

Background: The pathogenesis of major depressive disorder (MDD) is not unraveled. Involvement of the serotonin system is undoubted. More specifically the serotonin transporter (SERT) serves as a major target for antidepressant drugs. There are conflicting results about SERT availability in depressed patients versus healthy controls. We measured SERT and studied modifying effects of age, gender and other clinical variables in MDD patients versus healthy controls. Methods: Forty-nine depressed outpatients (42.3±8.3 [SD] years) with a Hamilton Depression Rating Scale above 18, who were drug-naive or drug-free for =4 weeks, and 49 age(±2 years) and sex-matched healthy controls were studied in a case-control design. Subjects were scanned with single photon emission computed tomography (SPECT) using [I]β-CIT. SERT availability was expressed as specific to nonspecific binding ratios (BDND) in midbrain (MID) and (hypo-) thalamus (THAL) with cerebellar binding as a reference. Results: In simple comparisons between patients and controls, we found no significant differences in SERT availability in MID or THAL. However, a significant interaction of gender on SERT in patients versus controls was found in MID (ANCOVA; p=0.048) and THAL (ANCOVA; p=0.012). Depressed males had lower, and depressed females higher SERT availability versus controls. In MID we found significant confounding by the season when patients were scanned (ANCOVA; p=0.017), with higher SERT availability in winter. Furthermore, patients with a current episode of N2 years seemed to have significant higher MID SERT availability than patients ill ≤2 years and healthy controls. Conclusion: This study points to a complex interaction of sex, season and the duration of the current episode of MDD on the serotonergic system in the pathogenesis of MDD, which should be considered in future studies.