Convergent functional effects of antidepressants in major depressive disorder: a neuroimaging meta-analysis.

Background: Neuroimaging studies have provided valuable insights into the macroscale impacts of antidepressants on brain functions in patients with major depressive disorder. However, the findings of individual studies are inconsistent. Here, we aimed to provide a quantitative synthesis of the literature to identify convergence of the reported findings at both regional and network levels and to examine their associations with neurotransmitter systems. Methods: Through a comprehensive search in PubMed and Scopus databases, we reviewed 5,258 abstracts and identified 36 eligible functional neuroimaging studies on antidepressant effects in major depressive disorder. Activation likelihood estimation was used to investigate regional convergence of the reported foci of consistent antidepressant effects, followed by functional decoding and connectivity mapping of the convergent clusters. Additionally, utilizing group-averaged data from the Human Connectome Project, we assessed convergent resting-state functional connectivity patterns of the reported foci. Next, we compared the convergent circuit with the circuits targeted by transcranial magnetic stimulation (TMS) therapy. Last, we studied the association of regional and network-level convergence maps with selected neurotransmitter receptors/transporters maps. Results: No regional convergence was found across foci of treatment-associated alterations in functional imaging. Subgroup analysis across the Treated > Untreated contrast revealed a convergent cluster in the left dorsolateral prefrontal cortex, which was associated with working memory and attention behavioral domains. Moreover, we found network-level convergence of the treatment-associated alterations in a circuit more prominent in the frontoparietal areas. This circuit was co-aligned with circuits targeted by "anti-subgenual" and "Beam F3" TMS therapy. We observed no significant correlations between our meta-analytic findings with the maps of neurotransmitter receptors/transporters. Conclusion: Our findings highlight the importance of the frontoparietal network and the left dorsolateral prefrontal cortex in the therapeutic effects of antidepressants, which may relate to their role in improving executive functions and emotional processing.