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

ABSTRACT

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 37 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 the selected neurotransmitter receptors/transporters maps. Results: We found regional convergence of the reported treatment-associated increases of functional measures in the left dorsolateral prefrontal cortex, which was associated with working memory and attention behavioral domains. No regional convergence was found across foci of alterations in functional imaging associated with antidepressants. Moreover, we found network-level convergence of functional alterations in a circuit that was prominent in the frontoparietal and salience networks. This circuit was co-aligned with a circuit targeted by anti-subgenual 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 left dorsolateral prefrontal cortex, as well as frontoparietal network and the salience network in the therapeutic effects of anti-depressants, possibly associated with their role in improving executive functions and emotional processing.