Dysregulation Of Stress Response Systems Research Articles

Association of childhood trauma with choice of bilateral mastectomy for the treatment of unilateral breast cancer.

e24096 Background: Patients are increasingly choosing bilateral mastectomy (BMX) for the treatment of primary breast cancer (BC) despite minimal survival benefits and potential for adverse medical and psychosocial consequences. Exposure to childhood trauma is associated with dysregulation of stress response systems, threat perception alterations, increased risk-taking behaviors, and body dissatisfaction. We examined childhood trauma in relation to treatment decision-making in adulthood within a sample of breast cancer patients undergoing either BMX or more conservative BC treatment. Methods: Secondary analyses of a case-control study of the neurobiological and affective determinants of BMX choice were conducted. Cross-sectional data from the baseline survey were analyzed. Participants were recruited via institutional clinic practices, social media, and patient advocacy groups. Patients completed a medical status questionnaire and the Childhood Trauma Questionnaire (CTQ). Chi-square and Mann-Whitney U tests examined differences in treatment decision-making by childhood trauma exposure and type. Results: The sample included 137 patients with unilateral stages 0-III BC (mean age 49.2; SD = 11.2; 76.6% White; 10.9% Hispanic/Latina; 68.6% married). Seven tested positive for a BRCA gene mutation. Patients were divided between BMX (n = 66) and non-BMX (n = 71) treatment groups. On average, patients in the non-BMX group reported higher levels of childhood trauma severity (Median = 7; IQR = 0-12.5) compared to patients in the BMX group (Median = 4; IQR = 0-11.75; Mann Whitney U = 4728; small effect size; SRD = -0.11; p = .26). Patients who reported a major parental upheaval (e.g., divorce, separation) were significantly more likely to pursue non-BMX compared to BMX (small effect size; SRD = -.16; p = .047). Patients who reported any uncategorized major upheaval were more likely to choose non-BMX than BMX (small effect size; SRD = -.14), but group differences did not reach significance (p = .093) . No other statistically significant relationships were observed. Conclusions: Contrary to hypotheses, preliminary results suggest BC patients who were exposed to traumatic events in childhood may be more likely to elect conservative BC surgical treatments. Trauma-related hypervigilance to threats may cause patients to exercise more caution regarding treatment choice. More research exploring the effects of adverse childhood experiences in the BC population is warranted. [Table: see text]

FKBP5 intron 7 methylation is associated with higher anxiety proneness and smaller right thalamus volume in adolescents.

Dysregulation of stress response systems may mediate the detrimental effects of childhood trauma (CT) on mental health. FKBP5 regulates glucocorticoid receptor sensitivity and exerts pleiotropic effects on intracellular signaling, neurobiology and behavior. We investigated whether CT, alone and in combination with rs1360780 genotype, is associated with altered FKBP5 methylation and whether CT-associated methylation profiles are associated with anxiety proneness (AP) and structural brain volumes. Ninety-four adolescents completed the Childhood Trauma Questionnaire, and a composite AP score was generated from the Childhood Anxiety Sensitivity Index and the State-Trait Anxiety Inventory-Trait measure. Mean methylation values for 12 regulatory regions and 25 individual CpG sites were determined using high-accuracy measurement via targeted bisulfite sequencing. FKBP5 rs1360780 genotype and structural MRI data were available for a subset of participants (n = 71 and n = 75, respectively). Regression models revealed an inverse association between methylation of three intron 7 CpG sites (35558438, 35558566 and 35558710) and right thalamus volume. CpG35558438 methylation was positively associated with AP scores. Our data indicate that an intron 7 methylation profile, consistent with lower FKBP5 expression and elevated high sensitivity glucocorticoid receptor levels, is associated with higher AP and smaller right thalamus volume. Research into the mechanisms underlying the intron 7 methylation-thalamus volume relationship, and whether it confers increased risk for long-term psychopathology by altering the regulatory threshold of stress responding, is required.

Externalizing and Internalizing Problems: Associations with Family Adversity and Young Children's Adrenocortical and Autonomic Functioning.

The development of child mental health problems has been associated with experiences of adversity and dysregulation of stress response systems; however, past research has largely focused on externalizing or internalizing problems (rather than their co-occurrence) and single physiological systems in high-risk adolescent samples. The present study examined whether cumulative family adversity, functioning in the hypothalamic-pituitary-adrenal axis (i.e., cortisol) and the parasympathetic nervous system (i.e., respiratory sinus arrhythmia [RSA]), and their interactions, predicted trajectories of co-occurring externalizing and internalizing problems among young children. Participants included 338 socioeconomically and racially diverse children (M age=5.32 years, SD=.32; male=51.8%) from a community sample. Family adversity (assessed with six measures) and child daily cortisol output and resting RSA were assessed in kindergarten. Parents, teachers, and children reported on children's externalizing and internalizing psychopathology up to three times from kindergarten to grade 1. Latent class growth analyses identified stable trajectories of externalizing and internalizing psychopathology. Trajectories were combined to create groups: co-occurring externalizing and internalizing (13.1%), externalizing-only (14.0%), internalizing-only (11.3%), and low problems (61.3%). Family adversity and resting RSA significantly positively predicted co-occurring group membership. Tests for interactions showed adversity did not significantly interact with physiological indicators to predict group membership. However, the two physiological systems interacted, such that higher and lower daily cortisol predicted internalizing group membership for children with lower and higher resting RSA, respectively. Findings support the importance of considering family context and multiple physiological systems to inform understanding of the development of mental health problems, and their co-occurrence, in early childhood.

Childhood adversity increases vulnerability for behavioral symptoms and immune dysregulation in women with breast cancer

Women respond differentially to the stress-associated with breast cancer diagnosis and treatment, with some women experiencing more intense and/or sustained behavioral symptoms and immune dysregulation than others. Childhood adversity has been identified to produce long-term dysregulation of stress response systems, increasing reactivity to stressors encountered during adulthood. This study determined whether childhood adversity increased vulnerability for more intense and sustained behavioral symptoms (fatigue, perceived stress, and depressive symptoms), poorer quality of life, and greater immune dysregulation in women (N=40) with breast cancer. Evaluation was after breast surgery and through early survivorship. Hierarchical linear modeling was used to examine intra-individual and inter-individual differences with respect to initial status and to the pattern of change (i.e. trajectory) of outcomes. At initial assessment, women exposed to childhood emotional neglect/abuse had greater perceived stress, fatigue, depressive symptoms and poorer quality of life, as well as lower natural killer cell activity (NKCA). Although these outcomes improved over time, women with greater childhood emotional neglect/abuse exhibited worse outcomes through early survivorship. No effect was observed on the pattern of change for these outcomes. In contrast, childhood physical neglect predicted sustained trajectories of greater perceived stress, worse quality of life, and elevated plasma IL-6; with no effect observed at initial assessment. Thus, childhood adversity leaves an enduring imprint, increasing vulnerability for behavioral symptoms, poor quality of life, and elevations in IL-6 in women with breast cancer. Further, childhood adversity predisposes to lower NKCA at a critical time when this immune-effector mechanism is most effective at halting nascent tumor seeding.