Perceived stress is associated with increased rostral middle frontal gyrus cortical thickness: a family‐based and discordant‐sibling investigation

Abstract

Background Elevated stress perception and depression commonly co-occur, suggesting that they share a common neurobiology. Cortical thickness of the rostral middle frontal gyrus (RMFG), a region critical for executive function, has been associated with depression- and stress-related phenotypes. Here, we examined whether RMFG cortical thickness is associated with these phenotypes in a large family-based community sample. Methods RMFG cortical thickness was estimated using FreeSurfer among participants (n=879) who completed the ongoing Human Connectome Project. Depression-related phenotypes (i.e., sadness, positive affect) and perceived stress were assessed via self-report. Results After accounting for sex, age, ethnicity, average whole-brain cortical thickness, twin status, and familial structure, RMFG thickness was positively associated with perceived stress and sadness and negatively associated with positive affect at small effect sizes (accounting for 0.2–2.4% of variance; p-fdr: 0.0051–0.1900). Perceived stress was uniquely associated with RMFG thickness after accounting for depression-related phenotypes. Further, among siblings discordant for perceived stress, those reporting higher perceived stress had increased RMFG thickness (p=4×10−7). Lastly, RMFG thickness, perceived stress, depressive symptoms, and positive affect were all significantly heritable with evidence of shared genetic and environmental contributions between self-report measures. Conclusions Stress perception and depression share common genetic, environmental, and neural correlates. Variability in RMFG cortical thickness may play a role in stress-related depression, though effects may be small in magnitude. Prospective studies are required to examine whether variability in RMFG thickness may function as a risk factor for stress exposure and/or perception, and/or arises as a consequence of these phenotypes.

Stress and the brain: Perceived stress mediates the impact of the superior frontal gyrus spontaneous activity on depressive symptoms in late adolescence

“…First, a whole‐brain correlation analysis was conducted to uncover the brain areas related to perceived stress. In light of prior findings of the neural bases of perceived stress (Holzel et al, ; Li et al, ; Michalski et al, ; Moreno et al, ; Piccolo et al, ; Rubin et al, ; Treadway et al, ; Wang et al, ; Zannas et al, ; Zimmerman et al, ), the fALFF in the PFC regions (e.g., SFG, MFG, and IFG) and limbic regions (e.g., amygdala and hippocampus) might be linked with perceived stress. Second, correlation analyses and mediation analyses were conducted to probe the associations between perceived stress, depressive symptoms, and resting‐state brain activity.…”

“…Thus, the brain bases of perceived stress may be manifested in the overall functional and structural brain differences, which could be detected more directly by using task‐free designs (e.g., RS‐fMRI and structural MRI [S‐MRI]) but not TB‐fMRI design (Biswal et al, ; Lerch et al, ; Mar, Spreng, & DeYoung, ), given that the TB‐fMRI is limited to the activity in areas related to a certain task (Kong, Ma, You, & Xiang, ; Kong, Wang, Hu, & Liu, ). Whereas many studies have used S‐MRI to examine the neurostructural basis of perceived stress (Holzel et al, ; Li et al, ; Michalski et al, ; Moreno et al, ; Piccolo et al, ; Rubin et al, ; Zannas et al, ; Zimmerman et al, ), few have used RS‐fMRI to explore the neurofunctional substrates underlying perceived stress. RS‐fMRI is a widely used neuroimaging method that can measure intrinsic brain activity and examine the neurofunctional bases underlying human behaviors (Biswal, ; Biswal et al, ; Raichle, ).…”

“…Furthermore, several longitudinal studies have shown that perceived stress can predict subsequent depressive symptoms in different populations (Chao, 2014;Lorenzo-Blanco & Unger, 2015;Rosal et al, 1997;Tsai & Chang, 2016). Additionally, evidence from twin investigations has uncovered a large genetic correlation between perceived stress and depressive symptoms (Bogdan & Pizzagalli, 2009;Michalski et al, 2017;Rietschel et al, 2014), suggesting that there is a common genetic basis underlying these two constructs. In summary, perceived stress might be a potential predictor of depressive symptoms.…”

“…Although the predictive role of perceived stress in depressive symptoms has been well established, less work has directly examined the neural mechanisms underlying perceived stress. Evidence from the existing literature has indicated that perceived stress is mainly associated with the functional and structural changes in the prefrontal cortex (PFC) (McEwen & Morrison, 2013;Michalski et al, 2017;Moreno, Bruss, & Denburg, 2017;Rubin et al, 2016;Treadway, Buckholtz, & Zald, 2013;Wang et al, 2005). For example, a perfusion fMRI study found that during a mental arithmetic stress task, perceived stress was correlated with cerebral blood flow changes in the ventral PFC (Wang et al, 2005).…”

“…Another task-based fMRI (TB-fMRI) study using a monetary incentive delay paradigm revealed that perceived stress was linked with the activity in the medial PFC (Treadway et al, 2013). Moreover, higher levels of perceived stress have been associated with structural alterations in the PFC regions, including the superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG) (Michalski et al, 2017;Moreno et al, 2017;Rubin et al, 2016). In addition to the PFC, some regions (e.g., amygdala and hippocampus) in the limbic system have been found to be crucial for perceived stress (Holzel et al, 2010;Li et al, 2014;Piccolo, Noble, & Gene, 2018;Tottenham & Sheridan, 2010;Zannas et al, 2013;Zimmerman et al, 2016).…”