Negative affect and stress‐related brain metabolism in patients with metastatic breast cancer

Abstract

Background Cancer and its treatment represent major stressors requiring that patients make multiple adaptations. Despite evidence that poor adaptation to stressors is associated with more distress and negative affect (NA), neuroimmune dysregulation and poorer health outcomes, current understanding is very limited of how NA covaries with central nervous system changes to account for these associations. Methods NA was correlated with brain metabolic activity using 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (18F‐FDG PET/CT) in several regions of interest in 61 women with metastatic breast cancer. Patients underwent 18F‐FDG PET/CT and completed an assessment of NA using the Brief Symptom Inventory. Results Regression analyses revealed that NA was significantly negatively correlated with the standardized uptake value ratio of the insula, thalamus, hypothalamus, ventromedial prefrontal cortex, and lateral prefrontal cortex. Voxel‐wise correlation analyses within these 5 regions of interest demonstrated high left‐right symmetry and the highest NA correlations with the anterior insula, thalamus (medial and ventral portion), lateral prefrontal cortex (right Brodmann area 9 [BA9], left BA45, and right and left BA10 and BA8), and ventromedial prefrontal cortex (bilateral BA11). Conclusions The regions of interest most strongly negatively associated with NA represent key areas for successful adaptation to stressors and may be particularly relevant in patients with metastatic breast cancer who are dealing with multiple challenges of cancer and its treatment.

Greater perceived stress management skills and heightened brain metabolic activity in cortical and subcortical stress processing regions in metastatic breast cancer patients

“…Symptom reduction in anxiety and depression is attributed to the strengthening of the more reflective, top-down cognitive control through increased activation of these brain regions (Clark & Beck, 2010 ). We thus hypothesize that lower activity of these brain regions such as lPFC, vmPFC, Ins, Hy and Th, which we previously found correlated with emotional distress in mBCa patients (13), may be reversed in persons with greater stress management skills for reducing negative mood and distress (Antoni & Dhabhar, 2019 ; Reis et al, 2020a , 2020b ). In other words, we hypothesize here that individual differences in PSMS efficacy are linked to upregulated metabolic activity in similar distress-related brain regions in women with mBC.…”

“…We provide evidence that higher reported perceptions of stress management skill (PSMS) efficacy relate significantly to more metabolic activity in the insula, thalamus, ventromedial and lateral prefrontal cortices, and basal ganglia. Of all these regions, the insula, thalamus, ventromedial and lateral prefrontal cortices regions have previously shown to show less activation in mBC patients reporting greater emotional distress (Reis et al, 2020a , 2020b ). Further analysis indicated that the association of PSMS with a priori ROIs were mostly specific to the cognitive coping subdomain of PSMS.…”

“…Identifying specific brain regions and networks that are sensitive to fluctuations in psychological states and perceptions of stress management skills, during the cancer journey can provide insights into the “hard-wiring” of a biobehavioral model of cancer, and may guide the development of more targeted psychosocial, behavioral, and pharmacological interventions to optimize psychological adaptation, quality of life, and health outcomes in cancer survivors (Reis et al, 2020a , 2020b ). For example, the sympathetic–adrenal–medullary (SAM) axis and the hypothalamic–pituitary–adrenal (HPA) axis are brain-body pathways that play a crucial role linking distress with physical health in general (Gianaros & Wager, 2015 ) and with cancer progression in particular (Antoni et al, 2006b ).…”

“…Neuroimaging studies that correlate emotional distress with neural circuitry in cancer patients find changes in function and structure of key brain regions such as the prefrontal cortex (PFC), thalamus (Th), amygdala (Amy), hippocampus (Hi), anterior cingulate cortex (ACC), hypothalamus (Hy), basal ganglia (BG, striatum and caudate) and insula (Ins) (Reis et al, 2020a , 2020b ). Recently, in metastatic breast cancer (mBC) patients, we reported that heightened emotional distress was significantly associated with reduced 18 F-fluorodeoxyglucose ( 18 F-FDG)-based brain metabolism in the Ins, Th, Hy, ventromedial (vm) PFC, and lateral (l) PFC (Reis et al, 2020a , 2020b ). One critical question is whether the subjective sense of being able to cope with stress, measured as PSMS efficacy, might rely on these same neural circuits, resulting in a greater activation of these brain regions.…”

Perceived efficacy of stress management skills, emotional distress, and diurnal cortisol in women with metastatic breast cancer.

“…The data of this study is part of a larger study (Travado et al, 2021) in which we examined the association of distress with brain metabolism in women with metastatic breast cancer. We found significantly negative correlations between distress and the activity of the insula, thalamus, hypothalamus, ventromedial prefrontal cortex and lateral prefrontal cortex, which represent key areas necessary for successful adaptation to stressors (Reis et al, 2020). The underactivity of these key brain regions associated with greater distress may contribute to dysregulation of the HPA axis and of cortisol basal diurnal rhythm.…”