Neural response to stress differs by sex in young adulthood

• Published in: Psychiatry research. Neuroimaging Vol. 332; p. 111646
• Main Authors: Cohen, Justine E., Holsen, Laura M., Ironside, Maria, Moser, Amelia D., Duda, Jessica M., Null, Kaylee E., Perlo, Sarah, Richards, Christine E., Nascimento, Nara F., Du, Fei, Zuo, Chun, Misra, Madhusmita, Pizzagalli, Diego A., Goldstein, Jill M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2023
• Subjects: Adolescent; Adult; Brain - diagnostic imaging; Cerebral Cortex - physiology; Female; Functional MRI; GABA MRS; gamma-Aminobutyric Acid; Gyrus Cinguli; Humans; Hydrocortisone; Male; MAST; MIST; Sex differences; Young Adult; Sex differences; MIST; Functional MRI; GABA MRS; MAST
• ISSN: 0925-4927; 1872-7506; 1872-7506
• DOI: 10.1016/j.pscychresns.2023.111646

•Brain activity and connectivity differs in young men and women under stress.•Task performance and affective response during stress did not differ between sexes.•However, under stress, women activated limbic, and in men cognitive control regions.•GABA in prefrontal cortex negatively associated with the brain activity by sex. 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.