Original Article

European Journal of Nuclear Medicine and Molecular Imaging

, Volume 36, Issue 5, pp 841-849

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

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

  • Henricus G. RuhéAffiliated withProgram for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of AmsterdamDepartment of Psychiatry, Academic Medical Center Email author 
  • , Jan BooijAffiliated withDepartment of Nuclear Medicine, Academic Medical Center, University of Amsterdam
  • , Johannes B. ReitsmaAffiliated withDepartment of Clinical Epidemiology, Biostatistics & Bioinformatics, Academic Medical Center, University of Amsterdam
  • , Aart H. ScheneAffiliated withProgram for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam



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 ≥4 weeks, and 49 healthy controls matched for age (±2 years) and sex. Subjects were scanned with single photon emission computed tomography (SPECT) using [123I]β-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 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.


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.


Serotonin transporter Single photon emission computed tomography Depressive disorder Healthy control Gender Season