Psychosocial Functioning and the Cortisol Awakening Response: Meta-Analysis, \u3cem\u3eP\u3c/em\u3e-Curve Analysis, and Evaluation of the Evidential Value in Existing Studies

Cortisol levels rise immediately after awakening and peak approximately 30-45 minutes thereafter. Psychosocial functioning influences this cortisol awakening response (CAR), but there is considerable heterogeneity in the literature. The current study used p-curve and metaanalysis on 709 findings from 212 studies to test the evidential value and estimate effect sizes of four sets of findings: those associating worse psychosocial functioning with higher or lower cortisol increase relative to the waking period (CARi) and to the output of the waking period (AUCw). All four sets of findings demonstrated evidential value. Psychosocial predictors explained 1%-3.6% of variance in CARi and AUCw responses. Based on these effect sizes, cross-sectional studies assessing CAR would need a minimum sample size of 617-783 to detect true effects with 80% power. Depression was linked to higher AUCw and posttraumatic stress to lower AUCw, whereas inconclusive results were obtained for predictor-specific effects on CARi. Suggestions for future CAR research are discussed

Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans

DNA methylation likely plays a role in the regulation of human stress reactivity. Here we show that in a genome-wide analysis of blood DNA methylation in 85 healthy individuals, a locus in the Kit ligand gene (KITLG; cg27512205) showed the strongest association with cortisol stress reactivity (P=5.8 � 10?6). Replication was obtained in two independent samples using either blood (N=45, P=0.001) or buccal cells (N=255, P=0.004). KITLG methylation strongly mediates the relationship between childhood trauma and cortisol stress reactivity in the discovery sample (32% mediation). Its genomic location, a CpG island shore within an H3K27ac enhancer mark, and the correlation between methylation in the blood and prefrontal cortex provide further evidence that KITLG methylation is functionally relevant for the programming of stress reactivity in the human brain. Our results extend preclinical evidence for epigenetic regulation of stress reactivity to humans and provide leads to enhance our understanding of the neurobiological pathways underlying stress vulnerability

Anxious to see you: Neuroendocrine mechanisms of social vigilance and anxiety during adolescence.

Social vigilance is a behavioral strategy commonly used in adverse or changing social environments. In animals, a combination of avoidance and vigilance allows an individual to evade potentially dangerous confrontations while monitoring the social environment to identify favorable changes. However, prolonged use of this behavioral strategy in humans is associated with increased risk of anxiety disorders, a major burden for human health. Elucidating the mechanisms of social vigilance in animals could provide important clues for new treatment strategies for social anxiety. Importantly, during adolescence the prevalence of social anxiety increases significantly. We hypothesize that many of the actions typically characterized as anxiety behaviors begin to emerge during this time as strategies for navigating more complex social structures. Here, we consider how the social environment and the pubertal transition shape neural circuits that modulate social vigilance, focusing on the bed nucleus of the stria terminalis and prefrontal cortex. The emergence of gonadal hormone secretion during adolescence has important effects on the function and structure of these circuits, and may play a role in the emergence of a notable sex difference in anxiety rates across adolescence. However, the significance of these changes in the context of anxiety is still uncertain, as not enough studies are sufficiently powered to evaluate sex as a biological variable. We conclude that greater integration between human and animal models will aid the development of more effective strategies for treating social anxiety