Objective

To determine whether structural and individual forms of stigma are associated with neurodevelopment in children.

Method

Stigma related to gender, race, and Latinx ethnicity was measured at the structural level using objective state-level indicators of social policies and prejudicial attitudes and at the individual level using self-reports of perceived discrimination. Respective associations of stigma with hippocampal volume and amygdala reactivity to threat were examined using data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 11,534, mean age 9.9 years), the first multisite neuroimaging study that provided substantial variability in sociopolitical contexts and that included individual-level measures of stigma among youth.

Results

In a preregistered analysis, Black (B = −58.26, p = .023) and Latinx (B = −40.10, p = .044) youths in higher (vs lower) structural stigma contexts were found to have smaller hippocampal volume, controlling for total intracranial volume, demographics, and family socioeconomic status. This association was also observed at a trend-level among girls (p = .082). The magnitude of the difference in hippocampal volume between high and low structural stigma states was equivalent to the predicted impact of a $20,000 difference in annual family income in this sample. As hypothesized, structural stigma was not associated with hippocampal volume in nonstigmatized youths, providing evidence of specificity. Perceived discrimination was unrelated to hippocampal volume in stigmatized groups. No associations between perceived discrimination or structural stigma and amygdala reactivity to threat were observed.

Conclusion

This study provides novel evidence that an objective measure of structural stigma may be more strongly related to hippocampal volume than subjective perceptions of stigma, suggesting that contextual approaches to stigma could yield new insights into neurodevelopment among marginalized youth.

IMPORTANCE Childhood adversity (CA) is a powerful determinant of long-term physical and mental health that is associated with elevated risk for chronic disease and psychopathology. However, the degree to which CA contributes to mortality as a preventable driver of ill-health and death is unknown.

OBJECTIVE To estimate the contribution of CA to health behaviors, including smoking and sedentary behavior, as well as the annual mortality attributable to CA in the US through influences on leading causes of death (eg, cardiovascular disease).

EVIDENCE REVIEW For this systematic review, the PsycINFO and MEDLINE databases were searched on November 15, 2019. The databases were searched for publications from inception (1806 for PsycINFO, 1946 for MEDLINE) to November 15, 2019. Meta-analyses of the associations between CA and morbidity outcomes were included. The population attributable fraction (PAF) was calculated from these associations along with the estimated US prevalence of CA. The PAF was then applied to the number of annual deaths associated with each cause of death to estimate the number of deaths that are attributable to CA. Additionally, the PAF was applied to the incidence of health behaviors to derive the number of cases attributable to CA. Exposure to 1 or more experiences of adversity before the age of 18 years was analyzed, including abuse, neglect, family violence, and economic adversity.

FINDINGS A total of 19 meta-analyses with 20 654 832 participants were reviewed. Childhood adversity accounted for approximately 439 072 deaths annually in the US, or 15% of the total US mortality in 2019 (2 854 838 deaths), through associations with leading causes of death (including heart disease, cancer, and suicide). In addition, CA was associated with millions of cases of unhealthy behaviors and disease markers, including more than 22 million cases of sexually transmitted infections, 21 million cases of illicit drug use, 19 million cases of elevated inflammation, and more than 10 million cases each of smoking and physical inactivity. The greatest proportion of outcomes attributable to CA were for suicide attempts and sexually transmitted infections, for which adversity accounted for up to 38% and 33%, respectively.

CONCLUSIONS AND RELEVANCE The results of this systematic review suggest that CA is a leading contributor to morbidity and mortality in the US and may be considered a preventable determinant of mortality. The prevention of CA and the intervention on pathways that link these e

IMPORTANCE Many studies have demonstrated an association between early-life adversity (ELA) and executive functioning in children and adolescents. However, the aggregate magnitude of this association is unknown in the context of threat and deprivation types of adversity and various executive functioning domains.

OBJECTIVE To test the hypothesis that experiences of deprivation are more strongly associated with reduced executive functioning compared with experiences of threat during childhood and adolescence.

DATA SOURCES Embase, ERIC, MEDLINE, and PsycInfo databases were searched from inception to December 31, 2020. Both forward and reverse snowball citation searches were performed to identify additional articles.

STUDY SELECTION Articles were selected for inclusion if they (1) had a child and/or adolescent sample, (2) included measures of ELA, (3) measured executive functioning, (4) evaluated the association between adversity and executive functioning, (5) were published in a peer-reviewed journal, and (6) were published in the English language. No temporal or geographic limits were set. A 2-reviewer, blinded screening process was conducted.

DATA EXTRACTION AND SYNTHESIS PRISMA guidelines were used to guide data extraction and article diagnostics (for heterogeneity, small study bias, and p-hacking). Article quality was assessed, and data extraction was performed by multiple independent observers. A 3-level meta-analytic model with a restricted maximum likelihood method was used. Moderator analyses were conducted to explore heterogeneity.

MAIN OUTCOMES AND MEASURES Primary outcomes included measures of the 3 domains of executive functioning: cognitive flexibility, inhibitory control, and working memory.

RESULTS A total of 91 articles were included, representing 82 unique cohorts and 31 188 unique individuals. Deprivation, compared with threat, was associated with significantly lower inhibitory control (F1,90 = 5.69; P = .02) and working memory (F1,54 = 5.78; P = .02). No significant difference was observed for cognitive flexibility (F1,36 = 2.38; P = .12). The pooled effect size of the association of inhibitory control with deprivation was stronger (Hedges g = −0.43; 95% CI, −0.57 to −0.29) compared with threat (Hedges g = −0.27; 95% CI, −0.46 to −0.08). The pooled effect size of the association of working memory with deprivation was stronger (Hedges g = −0.54; 95% CI, −0.75 to −0.33) compared with threat (Hedges g = −0.28; 95% CI, −0.51 to −0.05).

CONCLUSIONS AND RELEVANCE Experiences of both threat and deprivation in childhood and adolescence were associated with reduced executive functioning, but the association was stronger for exposure to deprivation. Efforts to address the consequences of ELA for development should consider the associations between specific dimensions of adversity and specific developmental outcomes.

Background:

Adolescence is a period of increased vulnerability for internalizing problems,

particularly following exposure to stressful life events. We examine how patterns of emotion regulation and brain structure and function predict internalizing problems during the COVID-19 pandemic, as well as moderate the association between pandemic-related stressors andvinternalizing problems.

Methods:

Data are from a longitudinal sample (N=145, aged 10-15) strategically assessed at three crucial timepoints: prior to the pandemic, early during the stay-at-home order period, and again six months later. We examined associations of neural structure and function during an emotional processing task prior to the pandemic, use of emotion regulation strategies prior to and during the pandemic, and pandemic-related stressors with internalizing problems.

Results:

Greater exposure to pandemic-related stressors was associated with higher levels of internalizing symptoms both early (ß = .437, p<.001) and later (ß = .225, p = .004) in the pandemic. Youth who reported more frequent use of maladaptive emotion regulation strategies, including rumination (ß = .204,p = .026) and expressive suppression (ß = .177, p = .023), also had higherinternalizing problems. Higher left amygdala activation to neutral relative to fearful faces prior tothe pandemic was associated with greater internalizing symptoms (ß =-.229, p = .007), and astrongerrelation between pandemic-related stressors and internalizing problems (ß = -.186, p = .014).

Conclusion:

Pandemic-related stressors are strongly associated with internalizing problems in adolescents, and individual differences in emotional reactivity and regulation and their underlying neural mechanisms contribute to stress-related vulnerability. Interventions that reduce pandemic-related stressors and foster adaptive emotion regulation skills may protect against adolescent psychopathology during this period of heightened exposure to stress.

Stressful life events (SLEs) are strongly associated with the emergence of adolescent anxiety and depression, but the underlying mechanisms remain poorly understood, especially at the within-persons level. We investigated how adolescent social communication (i.e., frequency of calls and texts) following SLEs relates to changes in internalizing symptoms in a multitimescale, intensive, year-long study (N = 30; n = 355 monthly observations; n ≈ 5,000 experience-sampling observations). Within-persons increases in SLEs were associated with receiving more calls than usual at both the month and moment levels and making more calls at the month level. Increased calls were prospectively associated with worsening internalizing symptoms at the month level only, suggesting that SLEs rapidly influence phone communication patterns, but these communication changes may have a more protracted, cumulative influence on internalizing symptoms. Finally, increased incoming calls prospectively mediated the association between SLEs and anxiety at the month level. We identify adolescent social communication fluctuations as a potential mechanism conferring risk for stress-related internalizing psychopathology.

There is a strong positive association between childhood socioeconomic status (SES) and academic achievement. This disparity may, in part, be explained by differences in early environmental experiences and language development. Cognitive stimulation—including language exposure, access to learning materials, caregiver involvement in children’s learning, and variety of experiences—varies by SES and may link SES to language development. Childhood language development in turn is associated with academic achievement. In the current longitudinal study of 101 children (60–75 months), SES was positively associated with cognitive stimulation and performance on language measures. Cognitive stimulation mediated the association between SES and children’s language. Furthermore, children’s language mediated the association between SES and academic achievement 18 months later. In addition to addressing broader inequalities in access to resources that facilitate caregivers’ abilities to provide cognitive stimulation, cognitive stimulation itself could be targeted in future interventions to mitigate SES-related disparities in language and academic achievement.

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = −0.111 to −0.068, FDR corrected P values \textless 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.

Although common sense suggests that we are motivated to pursue positive and avoid negative experiences, previous research shows that people regularly seek out negative experiences. In the current study, we characterized this tendency from childhood to young adulthood. Due to the known increases in risky behavior and sensation seeking in adolescence, we hypothesized that adolescents would show an increased engagement with negatively valenced stimuli compared to children and adults. Participants aged 4–25 (N = 192) completed a behavioral task assessing motivation to engage with negative, positive, and neutral images. On each trial, participants viewed two small images and selected one to view at a larger size for up to 10s. Trials were organized into three valence conditions: negative versus positive images (matched on arousal), negative versus neutral images, and positive versus neutral images. Although participants chose positive images more than neutral or negative images, participants selected negative images frequently, even when given a positive (28% of trials) or neutral (42% of trials) alternative. Contrary to expectations, the tendency to choose negative images was highest in early childhood and decreased linearly with increasing age, and the tendency to choose positive images increased linearly with age. These results provide insight into how motivation to engage with emotional stimuli varies across age. It is possible that the novelty and rarity of negative experiences drives children to pursue these stimuli. Alternatively, children may find negative images less aversive, which would caution against assuming that these stimuli elicit the same motivational states in individuals of all ages.

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18–83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen’s d = −0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.