1. Neural response to stress differs by sex in young adulthood.
- Author
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Cohen JE, Holsen LM, Ironside M, Moser AD, Duda JM, Null KE, Perlo S, Richards CE, Nascimento NF, Du F, Zuo C, Misra M, Pizzagalli DA, and Goldstein JM
- Subjects
- Humans, Male, Female, Young Adult, Adult, Adolescent, Brain diagnostic imaging, Gyrus Cinguli, gamma-Aminobutyric Acid, Hydrocortisone, Cerebral Cortex physiology
- Abstract
Increase in stress-related disorders in women begins post-puberty and persists throughout the lifespan. To characterize sex differences in stress response in early adulthood, we used functional magnetic resonance imaging while participants underwent a stress task in conjunction with serum cortisol levels and questionnaires assessing anxiety and mood. Forty-two healthy subjects aged 18-25 years participated (21M, 21F). Interaction of stress and sex in brain activation and connectivity were examined. Results demonstrated significant sex differences in brain activity with women exhibiting increased activation in regions that inhibit arousal compared to men during the stress paradigm. Women had increased connectivity among stress circuitry regions and default mode network, whereas men had increased connectivity between stress and cognitive control regions. In a subset of subjects (13F, 17M), we obtained gamma-aminobutyric acid (GABA) magnetic resonance spectroscopy in rostral anterior cingulate cortex (rostral ACC) and dorsolateral prefrotal cortex (dlPFC) and conducted exploratory analyses to relate GABA measurements with sex differences in brain activation and connectivity. Prefrontal GABA levels were negatively associated with inferior temporal gyrus activation in men and women and with ventromedial prefrontal cortex activation in men. Despite sex differences in neural response, we found similar subjective ratings of anxiety and mood, cortisol levels, and GABA levels between sexes, suggesting sex differences in brain activity result in similar behavioral responses among the sexes. These results help establish sex differences in healthy brain activity from which we can better understand sex differences underlying stress-associated illnesses., Competing Interests: Declaration of Competing Interest Dr. Goldstein is on the scientific advisory board and has an equity interest in Cala Health, a neuromodulation device company, but there is no conflict of interest with this study. The relationship is managed by the Mass General Brigham Office of Industry Interactions. Over the past 3 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 (for editorial work) and Alkermes; he has received research funding from the Brain and Behavior Research Foundation, the Dana Foundation, Millennium Pharmaceuticals, and National Institute of Mental Health (NIMH); he has received stock options from Compass Pathways, Engrail Therapeutics, Neumora Therapeutics, and Neuroscience Software. No funding from these entities was used to support the current work, and all views expressed are solely those of the authors. Dr. Misra has served on the advisory board of Ipsen and Abbvie and served as a consultant for Abbvie and Sanofi, but no conflicts of interest with this work. 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 have no financial disclosures., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2023
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