The serotonin transporter in depression: Meta-analysis of in vivo and post mortem findings and implications for understanding and treating depression

Abstract

BackgroundAltered serotonin transporter levels have been reported in blood and brain of patients with major depressive disorders. However, the strength and consistency of the evidence for altered serotonin transporter availability in major depressive disorder is not clear. MethodsTo address this, a comprehensive meta-analysis was conducted of all available in vivo neuroimaging and post mortem studies reporting serotonin transporter availability in patients with depression compared with healthy controls. ResultsThe final sample consisted of fifty (n=27 in vivo and n=25 post mortem) studies including 877 patients with depression (mean age: 42.9 years) and 968 healthy controls (mean age: 42.7 years). In vivo neuroimaging studies indicated reduced serotonin transporter binding in the striatum (g=−0.39, p=0.01), the amygdala (g=−0.37, p=0.01) and the brainstem (g=−0.31, p=0.01), including the midbrain (g=−0.27, p=0.02), but no significant alteration in the thalamus or the hippocampus. The post mortem findings indicated no significant change in serotonin transporter binding in depression in the brainstem (p=0.64), the frontal cortex (p=0.75) and the hippocampus (p=0.32, corrected for publication bias). Although there were too few studies for a meta-analysis, the post mortem studies in the amygdala and striatum showed reduced SERT binding in MDD in absolute terms, consistent with the imaging findings. LimitationsA number of potential factors might have biased the results of the present meta-analysis such as the imaging modality (post mortem or in vivo neuroimaging), partial volume effects, susceptibility of some radiotracers to synaptic serotonin levels or binding to other monoamine transporters. ConclusionsThe results indicate that serotonin transporter availability in depressed patients is reduced in key regions of the limbic system. This provides direct support for the serotonin hypothesis of depression, and underlines the importance of the serotonin transporter as a target of pharmacological treatments.