Association Between Neighborhood Violence and Biological Stress in Children.

Importance: Exposure to violence continues to be a growing epidemic, particularly among children. An enhanced understanding of the biological effect of exposure to violence is critical. Objective: To examine the association between neighborhood violence and cellular and biological stress in children. Design, Setting, and Participants: A matched, cross-sectional study of 85 black children aged 5 to 16 years from 52 neighborhoods took place in the greater New Orleans, Louisiana, area between January 1, 2012, and July 31, 2013. Exposures: Density of businesses where individuals can purchase alcohol as measured by rates per capita of liquor or convenience stores, and violence as measured by reports of violent crime and reports of domestic violence, operationalized as reports per capita of crime and domestic violence. Rates of exposure within a 500-, 1000-, and 2000-m radius from the child's home were calculated. Main Outcomes and Measures: Primary biological outcomes were telomere length and cortisol functioning. Results: Among the 85 children in the study, (mean [SD] age, 9.8 [3.1] years; 50 girls and 35 boys) significant variation in telomere length and cortisol functioning was observed at the neighborhood level, with intraclass correlation coefficients of 6% for telomere length, 3.4% for waking cortisol levels, and 5.5% for peak cortisol levels following a stressor. Density of liquor or convenience stores within a 500-m radius of a child's home was associated with a decrease in mean telomere length by 0.004 for each additional liquor store or convenience store (ß [SE], -0.004 [0.002]; P = .02). The rate of domestic violence was significantly and inversely associated with a decrease in mean telomere length by 0.007 for each additional report of domestic violence in a 500-m radius of a child's home (ß [SE], -0.007 [0.001]; P < .001). The rate of violent crime was significantly associated with a decrease in mean telomere length by 0.006 for each additional report of violent crime in a 500-m radius of a child's home (ß [SE], -0.006 [0.002]; P < .001). Children exposed to more liquor and convenience stores within 500 m of their home were significantly less likely to reduce cortisol levels after a reactivity test (ß, 0.029; P = .047), as were children exposed to high rates of domestic violence (ß, 0.088; P = .12) and violent crime (ß, 0.029; P = .006). Children exposed to more liquor and convenience stores within 500 m of their home had a steeper diurnal decline in cortisol levels during the day (ß [SE], -0.002 [0.001]; P = .04), as did children exposed to more violent crime within 500 m of their home (ß [SE] -0.032 [0.014]; P = .02). Conclusions and Relevance: Neighborhoods are important targets for interventions to reduce the effect of exposure to violence in the lives of children. These findings provide the first evidence that objective exposures to neighborhood-level violence influence both physiological and cellular markers of stress, even in children.

Diurnal and stress-reactive dehydroepiandrosterone levels and telomere length in youth.

The current investigation examined the association between the aging-related biomarkers dehydroepiandrosterone (DHEA) and telomere length (TL) in community-recruited African-American youth. The examination of DHEA included stress reactive, basal and diurnal sampling, in order to elucidate the underlying physiological process that may overlap with TL. One hundred and two participants completed the Trier Social Stressor Test for children (TSST-C). TL was obtained from all youth from buccal swabs on the same day as the TSST-C. Saliva samples from 83 participants were obtained over the course of two additional days to measure waking and diurnal levels of DHEA. DHEA diurnal slope was a robust predictor of TL (B=0.516, P<0.05), while other DHEA values were not significantly associated with TL. This study is one of the first studies to examine basal, diurnal and reactivity measurements of DHEA in youth. Furthermore, this is the first study, to our knowledge, to demonstrate a positive association between DHEA, a putative anti-aging hormone, and TL, an indicator of cellular aging.

A dual-axis approach to understanding neuroendocrine development.

This introduction sets out to present a series of paper about a novel perspective regarding stress and sex hormones, or what the authors within this special issue term "coupling" of hypothalamic-pituitary-adrenal and--gonadal axes. This view postulates that these axes do not necessarily operate in opposition, but can operate together as evidenced empirically as a positive within-person association between stress hormones like cortisol or sex hormones like testosterone. A wealth of papers within the special issue demonstrate positive coupling across acute, diurnal, basal, and longitudinal timeframes and across several different types of contexts. Reviews were meant to challenge whether this was physiologically plausible. Consistently, sophisticated statistical models were utilized in order to show a template for how to model positive coupling and to ensure that coupling was a within-person phenomenon. We cautiously considered positive coupling until the consistency of observing coupling was robust enough for us to consider challenging the prevailing oppositional view of these axes. We do so to acknowledge that there are contexts, moments and stages in which the function of these axes should work together: for example when contexts are both stressful and challenging or at developmental stages (like adolescence) in which the youth must grow up despite the storm and stress of youth. We hope that by putting forward a functional dual-axis approach, the field will be able to consider when and how these axes work together.

Context influences the interplay of endocrine axes across the day.

The current investigation examined stressors upon the coupling of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. Emphasis is placed on the moderating role of context and time. One hundred and eighteen adolescent males and females provided up to 32 diurnal saliva samples across a visit to a research lab. This visit constituted a day-long stress through which the impact on HPA-HPG axis coupling could be assessed. We tested four models of HPA-HPG axis coupling across the lab day. Sex and stress hormones operated synchronously (ß = .404, p < .001), and the coupling of sex and stress hormones was moderated by the stress of the lab day (ß = .010, p = .05). This pattern of co-elevation did not appear to be moderated by the distal experience of early life adversity. Findings suggest that the notion of "stress" must disentangle proximal and distal challenges, each of which appears to impact neurobiological processes.

Coupling of the HPA and HPG axes in the context of early life adversity in incarcerated male adolescents.

The effects of early life adversity can be observed across the lifespan, and the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes could be mechanistic intermediaries underlying this phenomenon. The current study examined 50 adolescent males aged 12-18 in a maximum-security correctional and treatment setting. Saliva samples were collected five times a day for 2 days and assayed for cortisol, testosterone, and DHEA. Youth completed semi-structured life stress interviews and self-reports of child maltreatment to index adversity. When youth had higher testosterone levels, they had higher cortisol and DHEA levels, indicating positive "coupling" of the HPA-HPG axes. In addition, children experiencing greater life adversity had tighter coupling of the HPA-HPG axes. Additional analyses hint that coupling may be driven largely by HPG axis functioning. Results indicate that positive coupling of the HPA-HPG axis is observed within incarcerated adolescents, especially for those with the greatest life stress.

Beyond physiological hypoarousal: the role of life stress and callous-unemotional traits in incarcerated adolescent males.

The development of antisocial behavior in youth has been examined with neurobiological theories that suggest that adolescents who are less responsive to their environments are less likely to develop empathy in the absence of extant physiological arousal. However, little attention is paid to these individuals' social context. Individuals with adverse early experiences can also exhibit attenuated physiological arousal. The current investigation examines whether psychopathic symptoms or life stress exposure is associated with cortisol and its diurnal rhythm within 50 incarcerated adolescent boys (14-18years old). Ten saliva cortisol samples were collected 1-2weeks after admission to a maximum-security juvenile facility. Hierarchical Linear Modeling distinguished waking cortisol levels, the awakening response (CAR) and the diurnal rhythm. Multiple interviews and self-report measures of CU traits and stressor exposure were collected. Boys with higher levels of CU traits or greater life stress exposure had flat diurnal rhythms and a steeper awakening response in analyses with lifetime stress exposure specifically. Nonetheless, boys who were elevated on both CU traits and prior stress exposure had steeper diurnal rhythms. These results extend neurobiological theories of cortisol and illustrate that boys with the combination of severe stress with CU traits have a unique physiological profile.

Psychopathy's influence on the coupling between hypothalamic-pituitary-adrenal and -gonadal axes among incarcerated adolescents.

Conduct disorder (CD) is a heterogeneous diagnosis, leading researchers to initiate studies focused on neurobiological mechanisms underlying this disorder. One specifier of CD currently considered for inclusion in the DSM-V is callous-unemotional (CU) traits, a key component of psychopathy. CU traits are thought to have neuroendocrine underpinnings, yet little is known about hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) hormones in the context of psychopathic traits. The current study sought to identify daily coupling patterns between HPA and HPG hormones in order to clarify distinct neurobiological underpinning associated with psychopathic/CU traits. Fifty incarcerated adolescent males who met criteria for CD were recruited and provided 10 saliva samples across 2 days. Participants completed the Psychopathy Checklist Youth Version (PCL:YV) and Inventory of Callous Unemotional Traits (ICU) on a third day. Diurnal cortisol, testosterone, and DHEA functioning was modeled via hierarchical linear modeling. Psychopathy subscales from the measures administered were used as predictors of daily coupling patterns between these hormones. Results indicated all three hormones were tightly coupled. Further, higher PCL-YV interpersonal scores related to greater coupling between all three hormones, whereas higher ICU callousness scores related to greater uncoupling of testosterone with cortisol and DHEA. The current study is novel in its emphasis on testing the coupling of HPA and HPG hormones among incarcerated adolescent males. Results suggest that affective and interpersonal psychopathic traits are marked by unique HPA- and HPG coupling.

Hormones: commentary. Riding the physiological roller coaster: adaptive significance of cortisol stress reactivity to social contexts.

The authors conjecture that to understand normal stress regulation, including cortisol stress reactivity, it is important to understand why these biomarkers are released and what they function to accomplish within the individual. This perspective holds that high (or rising) cortisol has advantages and disadvantages that must be understood within a context to understand how individual differences unfold. This perspective is juxtaposed with a popular vantage point of this stress hormone or of stress exposure that emphasizes the deleterious consequences or problems of this hormone. While the costs and benefits of cortisol are emphasized for normal stress regulation, this dynamic context-dependent purpose of stress hormones should extend to the development of psychopathology as well. This functional and dynamic view of cortisol is helpful for interpreting why Tackett and colleagues (2014) appear to observe advantageous cortisol recovery from stress in individuals with elevated personality disorder symptoms.