Multiscale neural signatures of major depressive, anxiety, and stress-related disorders

Author:

Zhukovsky Peter12ORCID,Wainberg Michael1ORCID,Milic Milos12,Tripathy Shreejoy J.123,Mulsant Benoit H.124ORCID,Felsky Daniel1245ORCID,Voineskos Aristotle N.12ORCID

Affiliation:

1. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada

2. Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5T 1R8, Canada

3. Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada

4. Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada

5. Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5S 1A8, Canada

Abstract

Significance Major depressive, anxiety, and stress-related disorders are highly comorbid and may affect similar neurocircuitry and cognitive processes. However, the neurocircuitry underlying shared dimensions of cognitive impairment is unclear and holds the promise of reimagining psychiatric nosology. Here we leverage population imaging data ( n = 27,132) to show that while major depressive and anxiety disorders share functional and structural neural signatures, stress-related disorders are distinct from these two conditions. We report that better cognitive function is associated with lower connectivity of specific nodes of the default mode and frontoparietal networks. These findings provide population benchmarks for brain–cognition associations in healthy participants and those with lifetime major depressive and anxiety disorders, advancing our understanding of intrinsic brain networks underlying cognitive dysfunction.

Funder

Labatt Family Fellowship in Depression Biology

Canadian Institute for Health Research

Michael and Sonja Koerner Foundation, Krembil Family Foundation, CAMH Discovery Fund, CIHR

Labatt Family Chair in Biology of Depression, Brain Canada, the Canadian Institutes of Health Research, the CAMH Foundation, the Patient-Centered Outcomes Research Institute

US National Institute of Health (NIH), Capital Solution Design LLC (software used in a study founded by CAMH Foundation), and HAPPYneuron

Eli Lilly (medications for a NIH-funded clinical trial) and Pfizer

Unpaid consultant to Myriad Neuroscience

CIHR, the NIH, the National Sciences and Engineering Research Council (NSERC), the CAMH Foundation, and the University of Toronto

CAMH Discovery Fund, Krembil Foundation, Kavli Foundation, McLaughlin Foundation, NSERC, CIHR, Simons Foundation Autism Research Initiative

CAMH Discovery Fund, Krembil Foundation, Kavli Foundation, McLaughlin Foundation, NSERC, CIHR,Simons Foundation Autism Research Initiative

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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