Changes in anterior cingulate connectivity associated with response to antidepressant treatment for major depressive disorder
- 1Center for Depression, Anxiety, and Stress Research, McLean Hospital, Belmont, MA, USA/University of California Irvine
Abstract
Background: Resting-state functional connectivity (rsFC) involving the anterior cingulate cortex (ACC) and the hippocampal formation has been implicated in major depressive disorder (MDD) and antidepressant response. However, it remains unclear whether connectivity changes in distinct ACC subdivisions and hippocampal formation reflect general antidepressant effects or are specifically associated with clinical improvement. Methods: Forty-one, unmedicated adults with MDD underwent functional MRI before and after 8 weeks of sertraline or bupropion treatment. Seed-based rsFC analyses examined subgenual ACC (sgACC), pregenual ACC (pgACC), dorsal ACC (dACC), and hippocampal formation connectivity. Linear mixed-effects models tested whether connectivity change was associated with treatment response, remission, and dimensional improvement in depressive symptoms. Results: Thirty individuals (73.2%) responded to treatment and 26 (63.4%) achieved remission. Overall, rsFC decreased pre- to post-treatment between (1) dACC and pgACC (but not sgACC and hippocampal formation) and (2) cortical regions primarily involving default mode and frontoparietal networks. When considering treatment response, differences in sgACC and pgACC connectivity with temporal and inferior frontal regions emerged (increased in responders vs. decreased in non-responders). Remission was similarly associated with increased sgACC connectivity with temporal and prefrontal regions, and increased sgACC connectivity with temporal cortical regions related to greater reductions in depressive symptoms. Conclusions: Antidepressant treatment was associated with distinct patterns of ACC connectivity change, with general reductions in dorsal and pregenual connectivity but increases in subgenual and pregenual connectivity associated with favorable clinical outcomes. Findings suggest that changes in sgACC/pgACC connectivity are particularly relevant to antidepressant treatment response. Keywords: Major depressive disorder; Resting-state functional connectivity; Anterior cingulate cortex; Antidepressant treatment; Treatment response; Subgenual anterior cingulate cortex.
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BibTeX
@misc{lam2026changes,
title = {{Changes in anterior cingulate connectivity associated with response to antidepressant treatment for major depressive disorder}},
author = {C. S. T. Lam and M. Kuhn and L. R. Borchers and B. Ren and S. E. Woronko and M. Li and E. M. Zhang and B. P. Brennan and G. Vitaliano and T. Lees and M. Bogdanov and N. P. Daskalakis and K. J. Ressler and P. Zhukovsky and D. A. Pizzagalli},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.29.762937},
url = {https://www.biorxiv.org/content/10.64898/2026.10.29.762937v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Changes in anterior cingulate connectivity associated with response to antidepressant treatment for major depressive disorder
AU - C. S. T. Lam
AU - M. Kuhn
AU - L. R. Borchers
AU - B. Ren
AU - S. E. Woronko
AU - M. Li
AU - E. M. Zhang
AU - B. P. Brennan
AU - G. Vitaliano
AU - T. Lees
AU - M. Bogdanov
AU - N. P. Daskalakis
AU - K. J. Ressler
AU - P. Zhukovsky
AU - D. A. Pizzagalli
PY - 2026
DA - 2026/10/29
PB - bioRxiv
DO - 10.64898/2026.10.29.762937
UR - https://www.biorxiv.org/content/10.64898/2026.10.29.762937v1
AB - Background: Resting-state functional connectivity (rsFC) involving the anterior cingulate cortex (ACC) and the hippocampal formation has been implicated in major depressive disorder (MDD) and antidepressant response. However, it remains unclear whether connectivity changes in distinct ACC subdivisions and hippocampal formation reflect general antidepressant effects or are specifically associated with clinical improvement. Methods: Forty-one, unmedicated adults with MDD underwent functional MRI before and after 8 weeks of sertraline or bupropion treatment. Seed-based rsFC analyses examined subgenual ACC (sgACC), pregenual ACC (pgACC), dorsal ACC (dACC), and hippocampal formation connectivity. Linear mixed-effects models tested whether connectivity change was associated with treatment response, remission, and dimensional improvement in depressive symptoms. Results: Thirty individuals (73.2%) responded to treatment and 26 (63.4%) achieved remission. Overall, rsFC decreased pre- to post-treatment between (1) dACC and pgACC (but not sgACC and hippocampal formation) and (2) cortical regions primarily involving default mode and frontoparietal networks. When considering treatment response, differences in sgACC and pgACC connectivity with temporal and inferior frontal regions emerged (increased in responders vs. decreased in non-responders). Remission was similarly associated with increased sgACC connectivity with temporal and prefrontal regions, and increased sgACC connectivity with temporal cortical regions related to greater reductions in depressive symptoms. Conclusions: Antidepressant treatment was associated with distinct patterns of ACC connectivity change, with general reductions in dorsal and pregenual connectivity but increases in subgenual and pregenual connectivity associated with favorable clinical outcomes. Findings suggest that changes in sgACC/pgACC connectivity are particularly relevant to antidepressant treatment response. Keywords: Major depressive disorder; Resting-state functional connectivity; Anterior cingulate cortex; Antidepressant treatment; Treatment response; Subgenual anterior cingulate cortex.
ER -