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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Cognitive-affective strategies and cortisol stress reactivity in children and adolescents: Normative development and effects of early life stress.

This study examined cognitive-affective strategies as predictors of hypothalamic-pituitary-adrenal (HPA) axis responses to a social-evaluative stressor in adolescence as compared to late childhood as a function of early life experiences. Participants included 159 children (9-10 years) and adolescents (15-16 years) divided into two groups based on early care experiences: non-adopted youth raised in their birth families (n = 81) and post-institutionalized youth internationally adopted from orphanage care (n = 78). Youth completed a version of the Trier Social Stress Test modified for use with children and reported on their trait emotion regulation and coping strategies. Children reported more use of suppression and disengagement than adolescents, while adolescents reported more engagement coping strategies. Non-adopted and post-institutionalized youth did not differ in reported strategies. Cognitive reappraisal predicted higher cortisol reactivity in non-adopted children and adolescents, and was not associated with reactivity in the post-institutionalized group. This study has implications for efforts aimed at promoting self-regulation and adaptive stress responses during the transition to adolescence for both typically developing children and children who experienced adverse early care.

Conceptualizing Puberty as a Window of Opportunity for Impacting Health and Well-Being Across the Life Span.

We promote the perspective that puberty, a separate biological process embedded in adolescence, is a "window of opportunity" for understanding and impacting health and development. First, we include a brief overview of pubertal change. Second, we propose a critical role for puberty in shaping life span health due to its connections with early life precursors, health issues and risks emerging during puberty, and health in young adulthood and beyond. Next, we discuss the importance of puberty measures in developmental research and suggest ways to make the science of puberty an important standalone research entity, as well as an essential component of studies conducted during adolescence. Finally, we discuss measurement issues, novel theoretical models of puberty, and the necessity of adopting an interdisciplinary perspective in research on puberty and in adolescence more broadly.

Longitudinal associations between attachment quality in infancy, C-reactive protein in early childhood, and BMI in middle childhood: preliminary evidence from a CPS-referred sample.

In the current pilot study, we examined whether insecure or disorganized attachment was associated with elevated inflammation (i.e. C-reactive protein [CRP]) in children with histories of child protective services (CPS) involvement, and whether early childhood CRP predicted body mass index (BMI) in middle childhood. Participants included 45 CPS-referred children and 39 low-risk comparison children, for whom we assessed levels of CRP in early childhood (Mean age = 4.9 years). For the CPS-referred children, who were drawn from an ongoing longitudinal study, we had attachment classifications (assessed during infancy with the Strange Situation) and BMI data (assessed during early and middle childhood); these data were not available for the low-risk comparison group. CPS-referred children who had insecure or disorganized attachments during infancy had higher levels of CRP in early childhood than CPS-referred children who had secure attachments, who had similar levels of CRP to low-risk comparison children. Among CPS-referred children, early childhood CRP predicted age 8 BMI, controlling for BMI at age 4. Findings offer preliminary support for the association between attachment quality and inflammation in early childhood, which may have implications for later physical health.

Racial/ethnic disparities in cortisol diurnal patterns and affect in adolescence.

Racial/ethnic minorities are more vulnerable to mental and physical health problems, but we know little about the psychobiological underpinnings of these disparities. In this study, we examined racial/ethnic differences in cortisol diurnal patterns and affect as initial steps toward elucidating long-term health disparities. A racially/ethnically diverse (39.5% White, 60.5% minority) sample of 370 adolescents (57.3% female) between the ages of 11.9 and 18 years (M = 14.65 years, SD = 1.39) participated in this study. These adolescents provided 16 cortisol samples (4 samples per day across 4 days), allowing the computation of diurnal cortisol slopes, the cortisol awakening response, and diurnal cortisol output (area under the curve), as well as daily diary ratings of high-arousal and low-arousal positive and negative affect. Consistent with prior research, we found that racial/ethnic minorities (particularly African American and Latino youth) exhibited flatter diurnal cortisol slopes compared to White youth, F (1, 344.7) = 5.26, p = .02, effect size g = 0.25. Furthermore, African American and Asian American youth reported lower levels of positive affect (both high arousal and low arousal) compared to White youth. Racial/ethnic differences in affect did not explain differences in cortisol patterns, suggesting a need to refine our models of relations between affect and hypothalamic-pituitary-adrenocortical activity. We conclude by proposing that a deeper understanding of cultural development may help elucidate the complex associations between affect and hypothalamic-pituitary-adrenocortical functioning and how they explain racial/ethnic differences in both affect and stress biology.

Future Directions in the Study of Early-Life Stress and Physical and Emotional Health: Implications of the Neuroimmune Network Hypothesis.

Early-life stress is associated with increased vulnerability to physical and emotional health problems across the lifespan. The recently developed neuroimmune network hypothesis proposes that one of the underlying mechanisms for these associations is that early-life stress amplifies bidirectional crosstalk between the brain and the immune system, contributing to several mental and physical health conditions that have inflammatory underpinnings, such as depression and coronary heart disease. Neuroimmune crosstalk is thought to perpetuate inflammation and neural alterations linked to early-life stress exposure, and also foster behaviors that can further compromise health, such as smoking, drug abuse and consumption of high-fat diets. The goal of the present review is to briefly summarize the neuroimmune network hypothesis and use it as a starting point for generating new questions about the role of early-life stress in establishing a dysregulated relationship between neural and immune signaling, with consequences for lifespan physical and emotional health. Specifically, we aim to discuss implications and future directions for theory and empirical research on early-life stress, as well as for interventions that may improve the health and well-being of children and adolescents living in adverse conditions.

Early-Life Socioeconomic Disadvantage and Metabolic Health Disparities.

OBJECTIVE: A quarter of the world's population have metabolic syndrome (MetS). MetS prevalence is stratified by socioeconomic status (SES), such that low SES is associated with higher MetS risk. The present study examined the relative roles of early-life SES and current SES in explaining MetS risk. METHODS: Participants (N = 354; ages = 15-55 years, M [SD] = 36.5 [10.7] years; 55% female; 72.9% white, 16.9% Asian, 10.2% others) were evaluated for SES and MetS. All were in good health, defined as free of chronic medical illness and acute infectious disease. Using occupational status as a proxy for SES, we recruited roughly equal numbers of participants with low-low, low-high, high-low, and high-high combinations of early-life and current SES. We used the International Diabetes Federation definition for MetS using race- and sex-specific cutoffs for waist circumference, triglyceride levels, high-density lipoprotein cholesterol, blood pressure, and glycosylated hemoglobin levels. RESULTS: Analyses revealed a main effect of low early-life SES on increased MetS risk according to the three separate definitions. They included the traditional MetS diagnosis (odds ratio [OR] = 1.53, confidence interval [CI] = 1.01-2.33, p = .044), the number of MetS components for which diagnostic thresholds were met (OR = 1.61, CI = 1.10-2.38, p = .015), and a continuous indicator of metabolic risk based on factor analysis (F(1,350) = 6.71, p = .010, partial η = .019). There was also a significant interaction of early-life SES and current SES in predicting MetS diagnosis (OR = 1.54, CI = 1.02-2.34). The main effects of current SES were nonsignificant in all analyses. CONCLUSIONS: These findings suggest that MetS health disparities originate in childhood, which may be an opportune period for interventions.

Threat vigilance and socioeconomic disparities in metabolic health.

A quarter of the global population meets diagnostic criteria for metabolic syndrome (MetS). MetS prevalence stratifies by socioeconomic status (SES), such that low SES is associated with higher MetS risk starting in childhood. Despite this trend, some low-SES children maintain good metabolic health across the life span, but the factors responsible for their resilience are not well understood. This study examined the role of threat vigilance as either a moderator or a mediator of the effects of low early life SES on adult metabolic risk. Three hundred twenty-five Canadians aged 15-55 participated (M = 36.4 years, SD = 10.7; 55.4% female). We coded parental occupational status between the ages of 0 and 5 to index early life SES. We used the International Diabetes Federation case definition for MetS based on waist circumference, blood pressure, triglyceride levels, HDL cholesterol, and glycosylated hemoglobin measures. Threat vigilance was assessed using the Weapons Identification Procedure, a visual discrimination paradigm that captures implicit perceptions of threat. Analyses supported the moderator hypothesis: low early life SES was associated with MetS diagnosis exclusively among those with high levels of threat vigilance. This suggests that low early life SES environments that heighten vigilance to threat might be particularly detrimental for metabolic health. Conversely, low threat vigilance may buffer against the metabolic risks associated with socioeconomic disadvantage.

Parent support is less effective in buffering cortisol stress reactivity for adolescents compared to children.

The goal of the present study was to investigate developmental differences in the effectiveness of parent support to alleviate hypothalamic-pituitary-adrenal (HPA) axis stress responses of children (ages 9-10, N = 40) and adolescents (ages 15-16, N = 41). We experimentally manipulated the provision of parent support during the speech preparation period before a modified Trier Social Stress Test (TSST) and examined its effect on levels of salivary cortisol secreted in response to this laboratory stressor. Analyses revealed a significant interaction of condition and age group such that social support from the parent (versus a stranger) significantly eliminated the cortisol stress response in children, but had no effect on the response among adolescents.

Associations between early life adversity and executive function in children adopted internationally from orphanages.

Executive function (EF) abilities are increasingly recognized as an important protective factor for children experiencing adversity, promoting better stress and emotion regulation as well as social and academic adjustment. We provide evidence that early life adversity is associated with significant reductions in EF performance on a developmentally sensitive battery of laboratory EF tasks that measured cognitive flexibility, working memory, and inhibitory control. Animal models also suggest that early adversity has a negative impact on the development of prefrontal cortex-based cognitive functions. In this study, we report EF performance 1 y after adoption in 2.5- to 4-y-old children who had experienced institutional care in orphanages overseas compared with a group of age-matched nonadopted children. To our knowledge, this is the youngest age and the soonest after adoption that reduced EF performance has been shown using laboratory measures in this population. EF reductions in performance were significant above and beyond differences in intelligence quotient. Within the adopted sample, current EF was associated with measures of early deprivation after controlling for intelligence quotient, with less time spent in the birth family before placement in an institution and lower quality of physical/social care in institutions predicting poorer performance on the EF battery.