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

Meta-analyses are one of the cornerstones of evidence-based medicine. This is especially true as pertains to clinical molecular imaging studies by single photon computed tomography (SPECT) and positron emission tomography (PET), many of which are underpowered due to their inherent expense and technical difficulty. For example, a formal analysis of the statistical power of [18F]fluorodeoxyglucose PET oncology studies highlighted the relationship between precision of the endpoint and the necessary group size for obtaining sensitivity to a 20% treatment effect (Doot et al., 2012). And yet, if sufficiently powered, molecular imaging can be the only way to obtain information about disease pathophysiology without confounds arising from ante mortem treatment and post mortem changes in the biomarker. The recent meta-analysis by Kambeitz and Howes (2015) reporting on the availability of plasma membrane serotonin transporters (SERT) in brain of patients with depressive disorders is a case in point; the summary yielded a total of 27 PET and SPECT imaging studies, comprising 514 patients and 555 healthy controls (although the composite group sizes reported in Results and Abstract differ), and revealed significantly lower SERT availability in several brain regions of the depression group. While the overall effect size (Hedges´ g) of approximately −0.3 is hardly pathognomonic of depression, the finding in such a large population confirms a long posited deficit or down-regulation of this marker of serotonin innervations (Spies et al., 2015), which furthermore could not be discerned in their additional meta-analysis of post mortem studies. The authors interpreted their results to support the importance of SERT as a molecular target for treatment of depression (despite the implication that most depressive patients have entirely normal SERT levels)..