Sex Differences in Stress Response Circuitry are Present in Early Adulthood: An fMRI Study of Healthy Young Adults

Justine Cohen, PhD

Massachusetts General Hospital
Sex Differences in Stress Response Circuitry are Present in Early Adulthood: An fMRI Study of Healthy Young Adults

Scientific Abstract

Background: Increased incidence of affective disorders in women begins post-puberty and is connected to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. To understand pathological changes in stress response circuitry, we must first understand sex differences in stress response in healthy young adults.

Methods: 42 healthy subjects aged 18-25 years (21F) underwent functional MRI while performing the Maastricht Acute Stress Test (MAST), in which subjects submerged a hand in ice-cold water while counting backward from 2043 in steps of 17, and Montreal Imaging Stress Task (MIST), in which subjects did math problems and received negative feedback. Subjects completed questionnaires before and after scanning that measured anxiety and mood. Whole brain (WB) and small volume correction (SVC) in regions of interest (ROIs) using two-sample t-tests compared brain activation and conditions between sexes. Functional connectivity was examined in seed-to-voxel analyses.

Results: Anxiety and mood before and after the task and cortisol response did not differ between men and women. Analyses comparing post-MAST to baseline showed women had increased activation in ventromedial PFC (pFWE<0.0001) in whole brain and ACC (pFWE=0.003) and mPFC (pFWE=0.002) in SVC. Functional connectivity showed men with increased connectivity between mPFC and R dorsolateral prefrontal cortex (dlPFC)(pFWE=0.05), and women with increased connectivity between mPFC and PCC pFWE<0.001), and ACC and PCC (pFWE<0.001). In analyses comparing post-MIST to baseline, men had increased activation in R precuneus (pFWE=0.002) and increased connectivity between L HIPP and L dlPFC (pFWE=0.05) and R HIPP and L dlPFC (pFWE=0.01) whereas women had increased connectivity between L AMYG and parietal regions.

Conclusions: Results highlight sex differences that implicate different strategies for inhibitory control of arousal. Collectively, these findings contribute to our understanding of sex differences in response to stress, from which we can better understand how this deviates in a sex-dependent way in MDD.

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research Areas


Justine Cohen, PhD, Laura Holsen, PhD, Maria Ironside, PhD, Amelia Moser, Christine Richards, Jessica Duda, Nara Nascimento, Madhusmita Misra, MD, Diego Pizzagalli, PhD, Jill Goldstein PhD

Principal Investigator

Jill Goldstein, PhD

Affiliated Website