Sex-related Differences in Stress Reactivity and Cingulum White Matter

Wheelock, Muriah D.; Goodman, Adam M.; Harnett, Nathaniel G.; Wood, Kimberly M.; Mrug, Sylvie; Knight, David C.

doi:10.1016/j.neuroscience.2021.02.014

Cited by 9 publications

(10 citation statements)

References 68 publications

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“…Additionally, GAF and sex were included as covariates of no interest in the linear mixed effects models. We included sex as a covariate due to known sex effects in stress response 36,37 . GAF was included as a covariate to control for potential variability in the severity of conditions that are not necessarily due to increased untreated duration between FS onset and diagnosis.…”

Section: Methodsmentioning

confidence: 99%

Precentral gyrus and insula responses to stress vary with duration to diagnosis in functional seizures

et al. 2022

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Objective: This study was undertaken to determine whether undiagnosed illness duration (time between functional seizures [FS] onset and diagnosis) is linked to differences in neural response and functional connectivity during processing of stressful experiences.Methods: Forty-nine participants with traumatic brain injury preceding the onset of FS confirmed by video-electroencephalography were recruited prospectively. Participants completed psychiatric symptom assessments before undergoing functional magnetic resonance imaging (fMRI) with an acute psychosocial stress task. Linear mixed effects (LME) analyses identified significant interactions between the factors of group (early vs. delayed diagnosis) and time lag to diagnosis on neural responses to stressful math performance and auditory feedback (corrected α = .05). Functional connectivity analysis utilized clusters from initial LME analyses as seed regions to determine significant interactions between these factors on network functional connectivity.Results: Demographic and psychiatric symptom measures were similar between early (n = 25) and delayed (n = 24) groups. Responses to stressful math performance within the left anterior insula and functional connectivity between the anterior insula seed region and a precentral gyrus cluster were significantly negatively correlated with time lag to diagnosis for the early but not the delayed FS diagnosis group. There was no correlation between fMRI findings and psychiatric symptoms.Significance: This study indicates that aberrant left anterior insula activation and its functional connectivity to the precentral gyrus underlie differences in processing of stressful experiences in patients with delayed FS diagnosis. Follow-up comparisons suggest changes are associated with undiagnosed illness duration rather than psychiatric comorbidities and indicate a potential mechanistic association between neuropathophysiology, response to stressful experiences, and

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Section: Methodsmentioning

confidence: 99%

Precentral gyrus and insula responses to stress vary with duration to diagnosis in functional seizures

et al. 2022

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“…This is consistent with prior research in adults showing that males have higher FA in the cingulum. Given evidence that microstructural properties of the tract are related to stress sensitivity differently in males and females (Wheelock et al., 2021 ), it is possible that lower morphometric cingulum properties in females contribute to or reflect sex differences in executive functioning in the context of stress. This is not to say that females have lower emotion regulatory abilities in general (e.g., due to sex‐linked genetic differences); rather, females experience greater interpersonal stressors (Hamilton et al., 2015 ) that impair their executive functioning (Shields et al., 2016 ) and increase their likelihood of developing internalizing forms of psychopathology, such as depression (Salk et al., 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…This interpretation is also consistent with prior work showing that while fiber cross‐section expansion occurs for all adolescents during pubertal development, males have larger white matter volume compared to females (Brouwer et al., 2012 ). It is possible that later in development, females may catch up to males in cingulum FDC, or that differences in this tract persist throughout adulthood and represent sex‐specific neural markers of stress sensitivity (Wheelock et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…adults (Wheelock et al, 2021), we hypothesized that, compared to males, females would exhibit lower micro-and macro-structural metrics (i.e., a combined measure of fiber density and cross-section (FDC) of the cingulum in early adolescence. We also expected that while males and females would not differ in depressive symptoms in early adolescence, females would exhibit steeper increases in symptoms over adolescence, reflecting a sex-related divergence in risk for depression (Salk et al, 2017).…”

Section: Key Pointsmentioning

confidence: 99%

“…The cingulum bundle may also act as a marker of resilience, given that higher FA in this tract has been associated with higher levels of “grit” in a geriatric sample (Vlasova et al., 2018 ). Finally, adult males have higher FA of the cingulum bundle than do females, which is related to stress reactivity differently in men and women (Wheelock et al., 2021 ). Collectively, these findings suggest that microstructural properties of the cingulum bundle contribute to sex differences in stress reactivity, resilience, and vulnerability to depression.…”

Section: Introductionmentioning

confidence: 99%

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Sex‐specific vulnerability to depressive symptoms across adolescence and during the COVID‐19 pandemic: The role of the cingulum bundle

Chahal

Miller

et al. 2022

JCPP Advances

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Background Females are at higher risk for developing depression during adolescence than are males, particularly during exposure to stressors like the COVID‐19 pandemic. Examining structural connections between brain regions involved in executive functioning may advance our understanding of sex biases in stress and depression. Here, we examined the role of the cingulum bundle in differentiating trajectories of depressive symptoms in males and females across adolescence and during the pandemic. Methods In a longitudinal study of 214 youth (121 females; ages 9–13 years at baseline), we examined whether fixel‐based properties of the cingulum bundle at baseline predict changes in females' and males' severity of depressive symptoms across four timepoints (4–7 years) in adolescence, including during the COVID‐19 pandemic. We also tested whether cingulum properties predict self‐reported resilience and stress during the pandemic. Results Females had lower fiber density and cross‐section (FDC) of the cingulum than did males, a neural pattern that predicted greater increases in depressive symptoms, lower resilience, and higher stress during the COVID‐19 pandemic. Cingulum morphometry predicted changes in depressive trajectories in females, but not in males; specifically, females with lower FDC had significant increases in symptoms throughout adolescence, whereas females with higher cingulum FDC did not. Conversely, males had low, stable depressive symptoms throughout adolescence and higher resilience and lower stress during the pandemic compared to females. Higher cingulum FDC predicted higher resilience and lower stress in both sexes. Conclusions In adults, the cingulum has been implicated in sex differences in stress reactivity. We show that in adolescents, the cingulum reflects sex differences in reports of stress and resilience that might contribute to the increased risk of stress‐related mood disorders in females. Adolescent females might benefit from cognitive interventions that strengthen the structural properties of the cingulum and increase their perceived resilience during periods of adversity and disruption.

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