Serotonin transporter binding with [123I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender

The serotonin system is undoubtedly involved in the pathogenesis of major depressive disorder (MDD). 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 aimed to measure SERT availability and study the effects of age, gender and season of scanning in MDD patients in comparison to healthy controls. We included 49 depressed outpatients (mean +/- SD 42.3 +/- 8.3 years) with a Hamilton depression rating scale score above 18, who were drug-naive or drug-free for a parts per thousand yen4 weeks, and 49 healthy controls matched for age (+/- 2 years) and sex. Subjects were scanned with single photon emission computed tomography (SPECT) using [I-123]beta-CIT. SERT availability was expressed as specific to nonspecific binding ratios (BPND) in the midbrain and diencephalon with cerebellar binding as a reference. In crude comparisons between patients and controls, we found no significant differences in midbrain or diencephalon SERT availability. In subgroup analyses, depressed males had numerically lower midbrain SERT availability than controls, whereas among women SERT availability was not different (significant diagnosisxgender interaction; p = 0.048). In the diencephalon we found a comparable diagnosisxgender interaction (p = 0.002) and an additional smokingxgender (p = 0.036) interaction. In the midbrain the season of scanning showed a significant main effect (p = 0.018) with higher SERT availability in winter. Differences in SERT availability in the midbrain and diencephalon in MDD patients compared with healthy subjects are affected by gender. The season of scanning is a covariate in the midbrain. The diagnosisxgender and genderxsmoking interactions in SERT availability should be considered in future studies of the pathogenesis of MDD.