Adolescents' hair cortisol concentrations during COVID-19: Evidence from two longitudinal studies in the Netherlands and the United States.

BACKGROUND: Prolonged stress exposure is associated with alterations in cortisol output. The COVID-19 pandemic represented a stressor for many, including children. However, a high-quality caregiving environment may protect against psychological problems and possibly against elevations in cortisol. We examined adolescents' physiological stress responses to the pandemic and the role of attachment in two longitudinal samples from the Netherlands and the United States (https://aspredicted.org/HHY_8MK). METHODS: Cortisol was assessed from hair samples before and during the pandemic, while attachment was self-reported prepandemic. Study 1 included a Dutch sample (N = 158; examined at ages 10 and later at 14 years old), whereas Study 2 included a US sample (N = 153; examined at ages 9-11 and again 2 years later) and an age-matched prepandemic sample (N = 29, 10-13 years old). Repeated-measures analyses of variance examined changes in cortisol from prepandemic to during the pandemic and the effect of attachment in each sample separately. RESULTS: After accounting for age, both studies revealed nonsignificant changes in hair cortisol and a nonsignificant effect of attachment. A significant effect of sex emerged in Study 1, with Dutch girls showing a significant cortisol increase during the pandemic, which was not explained by puberty. CONCLUSION: These findings suggest differential associations of the pandemic with hair cortisol increases by sex and country.

Understanding adolescent stress during the COVID-19 pandemic.

Longitudinal studies across the globe documented significant increases in psychological stress and mental health problems among adolescents during the COVID-19 pandemic. Health concerns, school disruptions, and social disconnection were major sources of stress. High levels of perceived stress predicted worse mental health outcomes, with girls, older adolescents, and socio-economically marginalized youth experiencing more pronounced mental health deteriorations. However, social support from family and peers was a protective factor against increased stress and accompanying mental health problems. We urge policymakers and other key decision-makers to improve the availability and financing of mental health services and support programs for adolescents to address the wave of mental health challenges following the pandemic.

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).

The Development of Shyness from Late Childhood to Adolescence: A Longitudinal Study of Mexican-origin Youth.

Shyness, the tendency to be inhibited and uncomfortable in novel social situations, is a consequential personality trait, especially during adolescence. The present study examined the development of shyness from late childhood (age 10) through adolescence (age 16) using data from a large, longitudinal study of Mexican-origin youth (N = 674). Using both self- and mother-reports of shyness assessed via the Early Adolescent Temperament Questionnaire-Revised, we found moderate to high rank-order stabilities across two-year intervals and a mean-level decrease in shyness from age 10 to 16. Anxiety and depression were associated with higher initial levels of shyness, and anxiety was associated with greater decreases in shyness from age 10 to 16. Contrary to predictions, neither nativity (country of birth) nor language proficiency (English, Spanish) was associated with the development of shyness across adolescence. Thus, youth generally decline in shyness during adolescence, although there is substantial individual variability in shyness trajectories.

A review of mental health disparities during COVID-19: Evidence, mechanisms, and policy recommendations for promoting societal resilience.

Social and economic inequality are chronic stressors that continually erode the mental and physical health of marginalized groups, undermining overall societal resilience. In this comprehensive review, we synthesize evidence of greater increases in mental health symptoms during the COVID-19 pandemic among socially or economically marginalized groups in the United States, including (a) people who are low income or experiencing homelessness, (b) racial and ethnic minorities, (c) women and lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ+) communities, (d) immigrants and migrants, (e) children and people with a history of childhood adversity, and (f) the socially isolated and lonely. Based on this evidence, we propose that reducing social and economic inequality would promote population mental health and societal resilience to future crises. Specifically, we propose concrete, actionable recommendations for policy, intervention, and practice that would bolster five "pillars" of societal resilience: (1) economic safety and equity, (2) accessible healthcare, including mental health services, (3) combating racial injustice and promoting respect for diversity, equity, and inclusion, (4) child and family protection services, and (5) social cohesion. Although the recent pandemic exposed and accentuated steep inequalities within our society, efforts to rebuild offer the opportunity to re-envision societal resilience and policy to reduce multiple forms of inequality for our collective benefit.

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.

Associations between peripheral inflammatory markers and amygdala activity and connectivity in response to emotional faces in adolescents.

Research in adults suggests that higher peripheral inflammation is associated with increased threat-related amygdala activity and reduced cortico-amygdala connectivity. However, there is limited research in adolescents, which is striking given the major developmental changes that occur in cortico-amygdala circuitry during adolescence. In this study, we examine the association between peripheral inflammation and amygdala activity and connectivity to emotional faces in a community sample of adolescents. Participants included 88 adolescents 12 to 15 years old who provided a blood sample and underwent fMRI scanning while completing a face and shape matching task that included fearful, angry, and happy faces. Blood samples were assayed for interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α); IL-6 and CRP were combined into a composite due to their high correlation and TNF-α was analyzed separately. Results indicated that higher TNF-α, but not the composite of IL-6 and CRP, was associated with increased amygdala activity to threatening (fearful and angry) faces and to happy faces, relative to shape matching. Whole-brain analyses also identified associations between TNF-α and neural activity to angry and happy faces in regions outside of the amygdala. Psychophysiological interaction analysis indicated that higher TNF-α was associated with reduced bilateral amygdala connectivity to the left cuneus, right cuneus/calcarine fissure/precuneus, and left supramarginal gyrus/inferior parietal gyrus during angry and fearful faces > shapes and higher IL-6/CRP was associated with reduced bilateral amygdala connectivity to the right postcentral gyrus and right precuneus. Results suggest that peripheral inflammation is associated with increased amygdala activity to emotional face stimuli and reduced amygdala connectivity with occipital and parietal regions. These findings enhance our understanding of the association between peripheral inflammation and neural response to emotional faces, which could inform the development of interventions targeting inflammation for adolescents.

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.

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.

Caregiver subjective and physiological markers of stress and patient heart failure severity in family care dyads.

Greater family caregiver exposure to uncontrolled patient symptoms is predictive of greater caregiver psychological and physiological stress in dementia and other chronic illnesses, but these phenomena have not been well-studied in heart failure (HF) - a disease with high symptom burden. The purpose of this study was to test the hypothesis that worse patient functional status (as reflected by increasing HF symptoms) would be associated with elevated psychological and physiological stress for the caregiver. This was a secondary analysis of data from 125 HF caregivers in the Caregiver Opportunities for Optimizing Lifestyle (COOL) study. Psychological stress was measured on four dimensions: care-related strain/burden (Oberst Caregiving Burden Scale), depression (Center for Epidemiological Studies Depression Scale), anxiety (State-Trait Anxiety Index), and general stress (Perceived Stress Scale). Physiological stress was measured by markers of HPA axis function (elevated cortisol awakening response [CAR]), endothelial dysfunction (increased PAI-1), and inflammation (increased IL-6, hsCRP). HF patient functional status was quantified by caregiver assessment of New York Heart Association (NYHA) Class. Generalized linear models were used to test associations between patient NYHA Class and stress (one model per indicator). NYHA Class (ordinal) was backwards difference coded in each model to examine caregiver stress in relation to increasing levels of HF severity. Caregivers were mostly female and in their mid-fifties, with a slight majority of the sample being African American and the patient's spouse. Overall, patient functional status was associated with greater caregiver psychological and physiological stress. In terms of psychological stress, higher NYHA Class was significantly associated with greater caregiver anxiety and general stress, but not with caregiver burden or depression. In terms of physiological stress, higher NYHA Class was associated with elevated markers in all models (elevated CAR and higher IL-6, hsCRP, and PAI-1). Across models, most associations between NYHA Class and stress were present at relatively early stages of functional limitation (i.e. Class II), while others emerged when functional limitations became more severe. To inform timing and mechanisms for much-needed caregiver interventions, research is needed to determine which aspects of HF symptomatology are most stressful for caregivers across the HF trajectory.

Hypothalamic-Pituitary-Adrenal Axis Activity in Childhood Predicts Emotional Memory Effects and Related Neural Circuitry in Adolescent Girls.

Negative emotional experiences can be more difficult to forget than neutral ones, a phenomenon termed the "emotional memory effect." Individual differences in the strength of the emotional memory effect are associated with emotional health. Thus, understanding the neurobiological underpinnings of the emotional memory effect has important implications, especially for individuals at risk for emotional health problems. Although the neural basis of emotional memory effects has been relatively well defined, less is known about how hormonal factors that can modulate emotional memory, such as glucocorticoids, relate to that neural basis. Importantly, probing the role of glucocorticoids in the stress- and emotion-sensitive period of late childhood to adolescence could provide actionable points of intervention. We addressed this gap by testing whether hypothalamic-pituitary-adrenal (HPA) axis activity during a parent-child conflict task at 11 years of age predicted emotional memory and its primary neural circuitry (i.e., amygdala-hippocampus functional connectivity) at 16 years of age in a longitudinal study of 147 girls (104 with complete data). Results showed that lower HPA axis activity predicted stronger emotional memory effects, r(124) = -.236, p < .01, and higher emotional memory-related functional connectivity between the right hippocampus and the right amygdala, ß = -.385, p < .001. These findings suggest that late childhood HPA axis activity may modulate the neural circuitry of emotional memory effects in adolescence, which may confer a potential risk trajectory for emotional health among girls.

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.

Adiposity, Inflammation, and Working Memory: Evidence for a Vicious Cycle.

Overweight and obesity constitute the fifth leading cause of preventable deaths worldwide. One pathway through which excess weight contributes to poor health outcomes is via inflammatory activity and changes in cognitive processes. Prior theory has proposed a vicious cycle whereby obesity potentiates inflammatory activity, which alters cognitive processes such as working memory, which in turn leads to a reduced ability to self-regulate and therefore manage weight. However, to date no longitudinal studies have examined this potential dynamic. In the current study, we addressed this gap by assessing the relations among fat mass, C-reactive protein (CRP), and working memory across time in a large sample of 8,536 children followed through adolescence in the Avon Longitudinal Study of Parents and Children in the United Kingdom. Adiposity was quantified via dual emission x-ray absorptiometry (DEXA) at ages 9 and 15.5 years old, and inflammatory activity was indexed via circulating serum C-reactive protein (CRP) levels assessed with a high-sensitivity assay at those same ages. Working memory was assessed between these two time points, at age 10, permitting examination of the temporal relations between working memory, adiposity, and inflammatory activity. As hypothesized, we found that fat mass predicted later poor working memory, and this association was statistically mediated by CRP. Further, we found that poor working memory predicted greater subsequent fat mass and CRP, and the link between working memory and subsequent CRP was partially mediated by fat mass. These results thus could be taken to suggest the existence of a vicious cycle of mutually amplifying adiposity, inflammatory activity, and poor working memory over time.

Associations between peripheral inflammation and resting state functional connectivity in adolescents.

Relatively little is known about associations between peripheral inflammation and neural function in humans. Neuroimaging studies in adults have suggested that elevated peripheral inflammatory markers are associated with altered resting state functional connectivity (rsFC) in several brain networks associated with mood and cognition. Few studies have examined these associations in adolescents, yet scarce data from adolescents point to different networks than adult studies. The current study examined the associations between peripheral inflammation and rsFC in a community sample of adolescents (n = 70; age, 12-15 years; 32 female, 36 male, 2 nonbinary). After blood sampling, an fMRI scan was performed to assess rsFC. Assay for serum inflammatory markers, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP), was performed. Results indicated that higher TNF-α was associated with altered rsFC between the right amygdala and left striatum and between the right inferior frontal gyrus and left parietal cortex (p < 0.05 whole-brain corrected). Associations with IL-6 and CRP were not significant. In contrast with findings in adults, inflammation may have unique links with the connectivity of the developing adolescent brain. Results have implications for understanding how peripheral inflammation may influence connectivity during adolescence, when neural networks are undergoing major developmental changes.

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.

The Role of Childhood Executive Function in Explaining Income Disparities in Long-Term Academic Achievement.

This study utilized data from the Avon Longitudinal Study of Parents and Children (N = 14,860) to examine whether early-life family income (age 0-5) predicted long-term academic achievement (age 16-18) and to investigate the role of executive function (EF) assessed multiple times across age 7-11 in explaining this association. Task-based EF was a significant mediator between early-life family income and later academic achievement in every model. This mediating pathway persisted when adjusting for a comprehensive panel of covariates including verbal IQ, sex, family income at ages 8 and 18, and early-life temperament. Additionally, teacher-rated and parent-rated EF mediated in some models. Overall, these findings suggest that childhood EF may play an important role in perpetuating income-based educational disparities.

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.