The role of stress phenotypes in understanding childhood adversity as a transdiagnostic risk factor for psychopathology.

Childhood adversity is a leading transdiagnostic risk factor for psychopathology, being associated with an estimated 31-62% of childhood-onset disorders and 23-42% of adult-onset disorders (Kessler et al., 2010). Major unresolved theoretical challenges stem from the nonspecific and probabilistic nature of the links between childhood adversity and psychopathology. The links are nonspecific because childhood adversity increases risk, through a range of mechanisms, for diverse forms of psychopathology and are probabilistic because not all individuals exposed to childhood adversity develop psychopathology. In this article, we propose a path forward by focusing on stress phenotypes, defined as biobehavioral patterns activated in response to stressors that can disrupt future functioning when persistent (e.g., reward seeking, social withdrawal, aggression). This review centers on the accumulating evidence that psychopathology appears to be more strongly predicted by behavior and biology during states of stress. Building on this observation, our theoretical framework proposes that we can model pathways from childhood adversity to psychopathology with greater specificity and certainty by understanding stress phenotypes, defined as patterns of behavior and their corresponding biological substrates that are elicited by stressors. This approach aims to advance our conceptualization of mediating pathways from childhood adversity to psychopathology. Understanding stress phenotypes will bring us closer to "precision mental health," a person-centered approach to identifying, preventing, and treating psychopathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Associations of air pollution with peripheral inflammation and cardiac autonomic physiology in children.

Climate change-related disasters have drawn increased attention to the impact of air pollution on health. 122 children ages 9-11 years old, M(SD) = 9.91(.56), participated. Levels of particulate matter (PM2.5) near participants' homes were obtained from the Environmental Protection Agency. Cytokines were assayed from 100 child serum samples: IL-6, IL-8, IL-10, and TNFα. Autonomic physiology was indexed by pre-ejection period (PEP), respiratory sinus arrhythmia (RSA), cardiac autonomic regulation (CAR), and cardiac autonomic balance (CAB). IL-6 was positively related to daily PM2.5 (r = .26, p = .009). IL-8 was negatively associated with monthly PM2.5 (r = -.23, p = .02). PEP was positively related to daily (r = .29, p = .001) and monthly PM2.5 (r = .18, p = .044). CAR was negatively associated with daily PM2.5 (r = -.29, p = .001). IL-10, TNFα, RSA, and CAB were not associated with PM2.5. Air pollution may increase risk of inflammation in children.

A systematic review and meta-analysis of the association between parenting and child autonomic nervous system activity.

Parental socialization may influence the development of children's autonomic nervous system (ANS), a key stress-response system. However, to date no quantitative synthesis of the literature linking parenting and child ANS physiology has been conducted. To address this gap, we conducted a pre-registered meta-analysis. A systematic review of the literature identified 103 studies (n = 13,044 participants) with available effect sizes describing the association between parenting and either parasympathetic nervous system (PNS) or sympathetic nervous system (SNS) activity in children. The overall analysis revealed non-significant associations between parenting and child ANS physiology on average. However, moderation analyses revealed a positive association between more positive parenting and higher resting PNS activity that was stronger when a study was experimental rather than correlational, and when the sample included children with a clinical condition. In conclusion, well-controlled experimental studies show that positive parenting is associated with the development of higher resting PNS activity, an effect that may be stronger among children who are at elevated developmental risk.

The cholinergic anti-inflammatory pathway in humans: State-of-the-art review and future directions.

The parasympathetic nervous system modulates inflammation through efferent vagus nerve signaling. Tracey (2002) termed this process as the cholinergic anti-inflammatory pathway (CAP). Interest in the potential practical use of this immune-modulatory process is increasing alongside increasing appreciation for the role of systemic inflammation in the etiology of somatic and psychological disease. A diverse literature exists providing expansive correlational evidence and some preliminary experimental evidence of the CAP in humans. However, so far this literature has not been well integrated and critically evaluated. This review describes the current state-of-the-art of research into vagus nerve driven parasympathetic control of inflammation in humans. Substantial limitations and gaps in the literature are identified, and promising directions for future research are highlighted.

Respiratory Sinus Arrhythmia as a Physiological Resilience Marker for Children's Health.

OBJECTIVE: The current study aimed to test parasympathetic nervous system activity, indexed through resting respiratory sinus arrhythmia (RSA) as a resilience factor that moderates the associations between socioeconomic status (SES), circulating cytokines, and somatic health in children. METHODS: The sample included 181 parent-child dyads (mean [standard deviation] child age = 9.91 [0.57] years; 50.3% boys). Parents reported on family income, parental education, and subjective social status, to index SES. Children provided serum samples for assaying circulating inflammatory cytokines and had RSA measured during a 5-minute seated resting period. We used a composite measure of inflammation that combined standardized measures of interleukin 6, interleukin 10, and tumor necrosis factor α. Parents reported on their child's global health impairment and number of chronic health conditions. RESULTS: Lower SES was associated with poorer global health, and higher levels of inflammation were associated with poorer global health, but these associations were not significant among children with high resting RSA. Specifically, resting RSA moderated the association between SES and global health impairment (B = 0.09, standard error [SE] = 0.02, p < .001). Preliminary evidence suggests that resting RSA may also moderate the association between inflammation and global health impairment (B = -0.12, SE = 0.03, p < .001), although this effect was no longer significant after Winsorizing an outlier value of a child with high global health impairment (B = -0.06, SE = 0.03, p = .04). CONCLUSIONS: High resting RSA may represent a physiological profile of resilience in children, weakening the associations between low SES and poor somatic health, and between greater inflammation and poor somatic health.

Heart Rate Variability and Circulating Inflammatory Markers in Midlife.

Theoretical perspectives and empirical evidence suggest that the parasympathetic nervous system engages in active monitoring and moderating of inflammatory processes. A clearer understanding of the bidirectional communication between the parasympathetic nervous system and the immune system could lead to novel clinical interventions for inflammatory illnesses. The current study used a large (N = 836) nationally representative sample of adults in the United States to investigate the relations between resting parasympathetic modulation of the heart, indexed through both high frequency heart rate variability (HF-HRV) and low frequency heart rate variability (LF-HRV), and six markers of circulating inflammation. Statistical analyses revealed robust inverse relations between HF-HRV and interleukin-6 (IL6), C-reactive protein (CRP), and fibrinogen, with or without covariate adjustment. Similar inverse relations were observed between LF-HRV and IL6 and CRP. No significant relations were observed between HRV and either inflammatory adhesion molecules (E-selectin, intracellular adhesion molecule-1) or soluble IL6 receptor. Results are consistent with the cholinergic anti-inflammatory pathway and suggest that parasympathetic modulation of inflammation through the vagus nerve may act on specific inflammatory molecules more than others.

Curvilinear associations between family income in early childhood and the cortisol awakening response in adolescence.

Previous evidence on cortisol output and socioeconomic status (SES) has been mixed, with studies finding that lower SES can be associated with higher or lower cortisol output, and null associations have also been reported. We hypothesized that these inconsistencies may be due to an underlying curvilinear, inverted-U pattern of association, such that low income is related to increased likelihood of both low and high cortisol output. We tested these curvilinear links among family income and cortisol indices in the Avon Longitudinal Study of Parents and Children (N = 803). Maternal reports of family income when the study children were 33 and 47 months of age were averaged to estimate early-childhood family income. Three cortisol indices were derived from samples collected in adolescence (15.5 years of age): the cortisol awakening response (CAR), area under the curve (AUC) cortisol, and the diurnal cortisol slope. As hypothesized, the CAR exhibited a curvilinear, inverted-U relation with childhood income, with low childhood income being associated with both the lowest and the highest CARs. These findings suggest that discrepancies in prior findings on low SES and the CAR may be due to curvilinear patterns of association. However, childhood income was not significantly associated with adolescent cortisol diurnal slope or AUC. Future work should clarify the factors that might predispose to high versus low CAR given equivalent low SES in childhood.

Children's altruism following acute stress: The role of autonomic nervous system activity and social support.

Altruistic behavior after stress exposure may have important health and psychological benefits, in addition to broader societal consequences. However, so far experimental research on altruism following acute stress has been limited to adult populations. The current study utilized an experimental design to investigate how altruistic donation behavior among children may be influenced by (a) exposure to an acute social stressor, the Trier Social Stress Test modified for use with children (TSST-M), (b) individual differences in stress physiology, and (c) social support from a parent. The sample consisted of 180 children (54.9% male, 45.1% female; mean age = 9.92 years, SD = 0.56 years) randomly assigned to one of three conditions involving the TSST-M: (a) prepare for the TSST-M alone, (b) prepare for the TSST-M with a parent, and (c) no-stress control group. Results revealed that children made larger donations post-stressor if they were alone before the acute stressor, if they had moderate cardiac autonomic balance, reflecting both parasympathetic and sympathetic influence, and if they were older. Children who prepared for the TSST-M with social support from a parent made comparable donations as children in the no-stress control group, in accord with stress buffering models. Increased altruism following acute stress among children suggests that a comprehensive understanding of the human stress response needs to incorporate "tend-and-befriend" behavior-the tendency for humans to show increased altruistic behavior during times of distress.

Childhood Parental Warmth and Heart Rate Variability in Midlife: Implications for Health.

The current study investigated high-frequency heart rate variability (HF-HRV) as a potential mediator between childhood parental warmth and later health and mortality outcomes. Participants were 1,255 adults (56.9% female). Childhood parental warmth was reported retrospectively at mean age 46; resting HF-HRV was measured at mean age 57; cardiovascular health and self-evaluated health were assessed at mean age 57 and 63, and mortality records extracted at mean age 63. Results revealed a positive association between childhood parental warmth and resting HF-HRV, as well as associations between higher HF-HRV and reduced risk of having a later cardiovascular health problem and of mortality by age 63. Mediation analyses revealed a small significant indirect effect of parental warmth, through HF-HRV, on cardiovascular health.

Autonomic nervous system activity predicts increasing serum cytokines in children.

Systemic inflammation is associated with increased risk for prevalent and costly diseases, and animal models implicate the autonomic nervous system in the control of inflammatory processes. In humans, research on autonomic-immune connections has been much more limited, and has focused on single branch autonomic measures (i.e., either parasympathetic or sympathetic). The current study utilized cardiac autonomic balance (CAB), derived from dual-branch cardiac autonomic recordings, to test the relation between resting autonomic function and inflammatory reactivity to challenge in children. METHODS: Participants included 96 children (51 boys, 45 girls) ages 9-11 years (mean age = 9.93 years, SD = 0.57 years). CAB values were calculated from standardized measures of parasympathetic and sympathetic activity, namely resting respiratory sinus arrhythmia and pre-ejection period data, respectively. Children provided two blood samples, one before and one following exposure to an acute social stressor or control condition. Serum was assayed for four cytokines that orchestrate inflammation: interleukin-6 (IL6), interleukin-8 (IL8), interleukin-10 (IL10), and tumor necrosis factor-alpha (TNFa). RESULTS: We discovered large individual differences in inflammatory marker production across children, and no average main effect of stress condition. CAB significantly predicted these individual differences, such that children lower on CAB showed increasing serum cytokines from time 1 to time 2. In contrast, children with greater CAB tended to show declining inflammatory markers across the session. DISCUSSION: Low cardiac autonomic balance (i.e., the combination of low parasympathetic and high sympathetic activity) may be a useful marker of proinflammatory tendencies in children, suggesting novel paths for early risk detection and intervention.

Prenatal maternal stress and child hair cortisol four years later: Evidence from a low-income sample.

BACKGROUND: Maternal stress during pregnancy can influence the trajectory of fetal development, shaping offspring physiology and health in enduring ways. Some research implicates fetal programming of the hypothalamic-pituitary-adrenocortical (HPA) axis as a mediator of these effects. The present study is the first to examine child hair cortisol concentration (HCC) and maternal stress during pregnancy in a diverse, low-income sample. METHODS: The sample consisted of 77 healthy, low-income (M annual income: $13,321), mother-children pairs (M child age = 3.81 years, SD = 0.43). The children were 57 % girls, 43 % boys. Mothers were 65 % Latina/Hispanic, 28 % Non-Hispanic White, 7% Black/African American. Maternal prenatal stress was measured with the Perceived Stress Scale administered by interview in the second and third trimesters, and again approximately four years later when child hair samples for assaying HCC were collected. RESULTS: On average maternal perceived stress increased significantly across pregnancy, then returned to lower levels 4 years after birth. Regression analysis revealed that child HCC was not significantly predicted by maternal perceived stress at either single prenatal time point. Exploratory analysis revealed evidence of a relation between increases in maternal prenatal stress from second to third trimester and child HCC four years later (r = .37, p =  .04). CONCLUSIONS: These results suggest that measures of prenatal maternal stress at any one time point may not be predictive of offspring long-term HPA output in low-income child samples, but that increases in stress levels across pregnancy may provide important information undetected by individual time point measures.

Parenting matters: Parents can reduce or amplify children's anxiety and cortisol responses to acute stress.

Parents serve important functions in regulating children's responses to stress and challenge. However, the parental characteristics that modulate the effectiveness of parents as stress buffers remain to be fully characterized. To address this gap, this study examined parental characteristics and behaviors that may explain variation in parents' ability to buffer cortisol responses to acute stress of 180 children (ages 9-11 years old, M = 9.9 years, SD = .58). Children were randomly assigned to either participate in a public speaking task, the Trier Social Stress Test - modified for children (TSST-M) or a control condition. Children in the TSST-M condition were randomly assigned to prepare for the public speaking task either with their parent (N = 59) or alone (N = 60), whereas 61 children were assigned to the control condition (no TSST-M). We found that parental education moderated the effect of condition on children's responses to acute stress. Children whose parents had lower levels of education exhibited reduced cortisol responses in the parent condition compared to the alone condition, showing a buffered pattern of reactivity. In contrast, children of parents with high levels of education displayed higher cortisol reactivity in the parent condition compared to the alone and control conditions. Parental education was also positively associated with higher levels of state anxiety within the parent condition. These results suggest that highly educated parents may emphasize performance over comfort, amplifying their children's state anxiety and cortisol responses to a public performance.