Abstract
Background: Neuroimaging studies have provided valuable insights into the macroscale impact 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, uti- lizing 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 to be 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.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
AS and SLV were funded by the Max Planck Society (Otto Hahn award) and Helmholtz Association Initiative and Networking Fund under the Helmholtz International Lab grant agreement InterLabs0015, and the Canada First Research Excellence Fund (CFREF Competition 2, 2015 2016) awarded to the Healthy Brains, Healthy Lives initiative at McGill University, through the Helmholtz International BigBrain Analytics and Learning Laboratory (HIBALL). SBE was supported by the Deutsche Forschungsgemeinschaft (DFG, EI 816/211), the National Institute of Mental Health (R01MH074457), and the European Union Horizon 2020 Research and Innovation Programme under Grant Agreement No. 945539 (HBP SGA3).
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
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The results of previous neuroimaging studies on the effects of antidepressants have been used.
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
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Footnotes
in the revised manuscript, we have: 1) used a random-effects rather than fixed-effects approach in our network-based meta-analysis and modified the test used in its association with resting-state networks, 2) removed one study using amesergide and therefore repeated all the analyses, 3) revised the analyses on the association of antidepressants meta-analytical effects with TMS targets and moved the corresponding figure to the main text, 4) revised parts of our introduction and discussion, 5) reorganized the supplements given the updates, and 6) provided additional details on the methods and publicly published our data and code at https://github.com/amnsbr/antidepressants_meta.
Data Availability
All data produced are available online. The coordinates of the foci reported in the included experiments are available at https://doi.org/10.6084/m9.figshare.24592539. The group-averaged dense resting-state functional connectivity matrix from the Human Connectome Project can be accessed at https://db.humanconnectome.org.
