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Sex-specific resting state brain network dynamics in patients with major depressive disorder

Neuropsychopharmacology volume 49, pages 806–813 (2024)Cite this article

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Abstract

Sex-specific neurobiological changes have been implicated in Major Depressive Disorder (MDD). Dysfunctions of the default mode network (DMN), salience network (SN) and frontoparietal network (FPN) are critical neural characteristics of MDD, however, the potential moderating role of sex on resting-state network dynamics in MDD has not been sufficiently evaluated. Thus, resting-state functional magnetic resonance imaging (fMRI) data were collected from 138 unmedicated patients with first-episode MDD (55 males) and 243 healthy controls (HCs; 106 males). Recurring functional network co-activation patterns (CAPs) were extracted, and time spent in each CAP (the total amount of volumes associated to a CAP), persistence (the average number of consecutive volumes linked to a CAP), and transitions across CAPs involving the SN, DMN and FPN were quantified. Relative to HCs, MDD patients exhibited greater persistence in a CAP involving activation of the DMN and deactivation of the FPN (DMN + FPN-). In addition, relative to the sex-matched HCs, the male MDD group spent more time in two CAPs involving the SN and DMN (i.e., DMN + SN- and DMN-SN + ) and transitioned more frequently from the DMN + FPN- CAP to the DMN + SN- CAP relative to the male HC group. Conversely, the female MDD group showed less persistence in the DMN + SN- CAP relative to the female HC group. Our findings highlight that the imbalance between SN and DMN could be a neurobiological marker supporting sex differences in MDD. Moreover, the dominance of the DMN accompanied by the deactivation of the FPN could be a sex-independent neurobiological correlate related to depression.

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Fig. 1: Co-activation patterns (CAPs) of interest.
Fig. 2: Group differences on time spent in CAPs and persistence.
Fig. 3: Group differences on transition probability from CAP7 to CAP4.

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Funding

This project was supported by the National Natural Science Foundation of China (82071532 to SY). Dr. Dong was funded by the Scientific Research Launch Project for new employees of the Second Xiangya Hospital of Central South University. Dr. Ironside has additional funding from the National Institute of Mental Health (NIMH; R01MH132565). Dr. Belleau is supported by funding from the National Institute of Mental Health (K23MH122668) and the Klingenstein Third Generation Foundation. The content is solely the responsibility of the authors. The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China

    Daifeng Dong, Xiaocui Zhang, Chuting Li, Xiaoqiang Sun, Ge Xiong, Chang Cheng, Xiang Wang & Shuqiao Yao

  2. China National Clinical Research Center for Mental Disorders (Xiangya), Changsha, Hunan, PR China

    Daifeng Dong, Xiaocui Zhang, Chuting Li, Xiaoqiang Sun, Ge Xiong, Chang Cheng, Xiang Wang & Shuqiao Yao

  3. McLean Hospital, Belmont, MA, USA

    Diego A. Pizzagalli, Maria Ironside & Emily L. Belleau

  4. Harvard Medical School, Boston, MA, USA

    Diego A. Pizzagalli, Maria Ironside & Emily L. Belleau

  5. Connectomics Laboratory, Department of Radiology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

    Thomas A. W. Bolton

  6. Laureate Institute for Brain Research, Tulsa, OK, USA

    Maria Ironside

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  1. Daifeng Dong
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Contributions

SY, ELB, DAP, and XW conceptualized the study; SY, XW, DD, XZ, CL, XS, GX, and CC collected the data; DD, ELB, TAWB, DAP, and MI analyzed the data and interpreted the data. DD drafted the manuscript with critical revisions from ELB, DAP, TAWB, and MI. All authors approved the final manuscript and are accounted for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Shuqiao Yao or Emily L. Belleau.

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Competing interests

Over the past three years, Dr. Pizzagalli has received consulting fees from Albright Stonebridge Group, Boehringer Ingelheim, Compass Pathways, Engrail Therapeutics, Neumora Therapeutics (formerly BlackThorn Therapeutics), Neurocrine Biosciences, Neuroscience Software, Otsuka, Sunovion, and Takeda; he has received honoraria from the Psychonomic Society and American Psychological Association (for editorial work) and from Alkermes; he has received research funding from the Brain and Behavior Research Foundation, Dana Foundation, Millennium Pharmaceuticals, and Wellcome Leap; he has received stock options from Compass Pathways, Engrail Therapeutics, Neumora Therapeutics, and Neuroscience Software. There are no conflicts of interest with the work conducted in this study. No funding from these entities was used to support the current work, and all views expressed are solely those of the authors. The other authors report no financial relationships with commercial interests.

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Dong, D., Pizzagalli, D.A., Bolton, T.A.W. et al. Sex-specific resting state brain network dynamics in patients with major depressive disorder. Neuropsychopharmacol. 49, 806–813 (2024). https://doi.org/10.1038/s41386-024-01799-1

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