The serotonergic system may play an important role in the pathophysiology of major depressive disorder (MDD). Few imaging studies have examined serotonin transporter (SERT) binding in patients with MDD. We hypothesized that SERT binding activity may be altered in patients with MDD. This study compared SERT binding in patients with MDD with that in healthy controls. METHODS: We studied SERT activity in 7 patients (22-50 y old) with moderate to severe MDD and 6 healthy controls (24-56 y old) using (123)I-labeled 2-((2-((dimethylamino)methyl) phenyl)thio)-5-iodophenylamine (ADAM) and SPECT brain imaging. Subjects underwent SPECT 4 h after intravenous administration of 185 MBq (5 mCi) of (123)I-ADAM. Images were reconstructed in the axial plane, and region-of-interest demarcations were placed on the midbrain, medial temporal region, and basal ganglia region. RESULTS: (123)I-ADAM binding to SERT in the midbrain was significantly lower (P = 0.01) in MDD patients (1.81 +/- 0.07) than in controls (1.95 +/- 0.13). Age-adjusted (123)I-ADAM binding in the midbrain correlated significantly with scores on the Hamilton Depression Rating Scale (r = 0.82; P = 0.02). A significant negative correlation was observed between (123)I-ADAM SERT binding in the midbrain and age in the healthy control group (r = 0.98; P = 0.0002). SERT binding in the basal ganglia or medial temporal regions of interest did not significantly differ between groups. CONCLUSION: The findings from this preliminary study suggest the possibility of decreased SERT binding in the midbrain region of patients with MDD, with the degree of decrease correlating with the severity of depressive symptoms. There also appears to be an age-related decline in midbrain (123)I-ADAM SERT binding in healthy subjects.
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