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

Abstract

Purpose 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. Methods 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 ≥4 weeks, and 49 healthy controls matched for age (±2 years) and sex. Subjects were scanned with single photon emission computed tomography (SPECT) using [ 123 I]β-CIT. SERT availability was expressed as specific to nonspecific binding ratios (BP ND ) in the midbrain and diencephalon with cerebellar binding as a reference. Results 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 diagnosis×gender interaction; p=0.048). In the diencephalon we found a comparable diagnosis×gender interaction (p=0.002) and an additional smoking×gender (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. Conclusion 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 diagnosis×gender and gender×smoking interactions in SERT availability should be considered in future studies of the pathogenesis of MDD.

Imaging the effects of genetic polymorphisms on radioligand binding in the living human brain: A review on genetic neuroreceptor imaging of monoaminergic systems in psychiatry

“…Using [ 11 C]DASB and PET, we were able to show that serotonin transporter binding varies across seasons, with highest binding measured in fall and winter, and lower binding measured in spring and summer, with peak differences being as high as 40% (Praschak-Rieder et al, 2008). A seasonal variation in brain serotonin transporter binding has also been found with [ 11 C]McN 5652 and PET (Buchert et al, 2006), and with [ 123 I]β-CIT and SPECT (Ruhe et al, 2009), as well as in another recent study using [ 11 C]DASB and PET (Kalbitzer et al, 2010). These studies unanimously show that serotonin transporter binding is higher in fall and winter as compared to spring and summer.…”

Altered serotonin and dopamine transporter availabilities in brain of depressed patients upon treatment with escitalopram: A [123I]β-CIT SPECT study

“…Furthermore, SERT availability might be confounded by factors such as gender (Staley et al, 2001) and smoking habits (although less than one third of our patients reported smoking). We saw no effect of season on baseline SERT availability in our cohort, whereas such an influence was recently reported in an earlier study in a large patient group (Ruhe et al, 2009a).…”

Assessing the Optimal Time Point for the Measurement of Extrastriatal Serotonin Transporter Binding with 123I-FP-CIT SPECT in Healthy, Male Subjects

“…We performed measurements on healthy subjects. Because several medical conditions can influence brain SERT (e.g., Parkinson disease and Lewy bodies dementia (5,6), panic disorder (19), and depression (22,23)), it is unknown at present whether peak extrastriatal SERT binding of 123 I-FP-CIT is similar in subjects with any of these diseases. This topic also needs further investigation.…”