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Sex-specific neural responses to acute psychosocial stress in depression.

ABSTRACT: Major Depressive Disorder (MDD) is characterized by increased stress sensitivity. Emerging findings in healthy adults suggest that stress responses within limbic/striatal-prefrontal regions are moderated by sex and unfold over time. Thus, we hypothesized that stress response abnormalities in MDD might be affected by sex and stress exposure time. The Montreal Imaging Stress Task was administered to 124 unmedicated patients with first-episode MDD (76 females) and 243 healthy controls (HC; 137 females) during functional magnetic resonance imaging (fMRI). Based on prior studies, amygdala, hippocampus, medial orbitofrontal cortex (mOFC), nucleus accumbens (NAc) and dorsolateral prefrontal cortex (dlPFC) were selected as a priori regions of interest. In a complementary approach, we probed the effects of stress on the frontoparietal network (FPN) and a network including the amygdala, NAc and anterior cingulate cortex (ACC). Across groups, males exhibited higher dlPFC activity and right FPN amplitude than females. Relative to female HCs, the female MDD group had less deactivation in limbic/striatal regions (amygdala, NAc, hippocampus, Amygdala-NAc-ACC network). Furthermore, unlike female HCs, the female MDD group failed to show a significant increase of deactivation over stress exposure time in the amygdala, mOFC and NAc. Our findings confirm the importance of considering sex differences when investigating neural stress responses. Case-control differences in neural stress responses observed in females (but not males) provide insights into sex differences in the etiology and pathophysiology of depression. The failure to deactivate limbic/NAc regions in depressed females point to dysfunction of adaptive stress responses over stress exposure time.

SUBMITTER: Dong D

PROVIDER: S-EPMC8748634 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:FMRI Montreal Imaging Stress Tasks (MIST) have been shown to activate endocrine and autonomic stress responses that are mediated by a prefrontal cortex (PFC)-hippocampus-amygdala circuit. However, the stability of the neurobehavioral responses over time and the ability to monitor response to clinical interventions has yet to be validated. The objective of this study was to compare the fMRI and physiologic responses to acute psychosocial stress in healthy volunteers during initial and follow-up visits approximately 13 weeks later, simulating a typical duration of clinical intervention. We hypothesized that responses to stress would remain highly conserved across the 2 visits in the absence of an intervention. 15 healthy volunteers completed a variant of control math task (CMT) and stress math task (SMT) conditions based on MIST. Neural responses were modeled using an event-related design with estimates for math performance and auditory feedback for each task condition. For each visit, measures of stress reactivity included differential fMRI and heart rate (SMT-CMT), as well as salivary alpha-amylase before and after scanning sessions. The results revealed that differential fMRI, as well as increased heart rate and salivary alpha-amylase from before and after scanning remained similar between visits. Intraclass correlation coefficient (ICC) values revealed areas of reliable task-dependent BOLD fMRI signal response across visits for peaks of clusters for the main effect of condition (SMT vs CMT) within dorsal anterior cingulate cortex (ACC), insula, and hippocampus regions during math performance and within subgenual ACC, posterior cingulate cortex, dorsolateral PFC regions during auditory feedback. Given that the neurobehavioral response to acute stress remained highly conserved across visits in the absence of an intervention, this study confirms the utility for MIST for assessing longitudinal changes in controlled trials that can identify underlying neurobiological mechanisms involved in mediating the efficacy of stress-reduction interventions.

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Sex-specific neural responses to acute psychosocial stress in depression.

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