The environment has pervasive impacts on human development, and two key environmental conditions – harshness and unpredictability – are proposed to be instrumental in tuning development. This study examined (1) how harsh and unpredictable environments related to immune and clinical outcomes in the context of childhood asthma, and (2) whether there were independent associations of harshness and unpredictability with these outcomes. Participants were 290 youth physician-diagnosed with asthma. Harshness was assessed with youth-reported exposure to violence and neighborhood-level murder rate. Unpredictability was assessed with parent reports of family structural changes. Youth also completed measures of asthma control as well as asthma quality of life and provided blood samples to assess immune profiles, including in vitro cytokine responses to challenge and sensitivity to inhibitory signals from glucocorticoids. Results indicated that harshness was associated with more pronounced pro-inflammatory cytokine production following challenge and less sensitivity to the inhibitory properties of glucocorticoids. Furthermore, youth exposed to harsher environments reported less asthma control and poorer quality of life. All associations with harshness persisted when controlling for unpredictability. No associations between unpredictability and outcomes were found. These findings suggest that relative to unpredictability, harshness may be a more consistent correlate of asthma-relevant immune and clinical outcomes.

Psychosocial stress in childhood and adolescence is linked to stress system dysregulation, although few studies have examined the relative impacts of parental harshness and parental disengagement. This study prospectively tested whether parental harshness and disengagement show differential associations with overall cortisol output in adolescence. Associations between overall cortisol output and adolescent mental health problems were tested concurrently. Adolescents from the Fragile Families and Child Wellbeing Study (FFCWS) provided hair samples for cortisol assay at 15 years (N = 171). Caregivers reported on parental harshness and disengagement experiences at 1, 3, 5, 9, and 15 years, and adolescents reported at 15 years. Both parent and adolescent reported depressive and anxiety symptoms and antisocial behaviors at 15. Greater parental harshness from 1–15 years, and harshness reported at 15 years in particular, was associated with higher overall cortisol output at 15. Greater parental disengagement from 1–15 years, and disengagement at 1 year specifically, was associated with lower cortisol output. There were no significant associations between cortisol output and depressive symptoms, anxiety symptoms, or antisocial behaviors. These results suggest that the unique variances of parental harshness and disengagement may have opposing associations with cortisol output at 15 years, with unclear implications for adolescent mental health.

While previous studies suggest that both genetic and environmental factors play an important role in the development of autism-related traits, little is known about potential biological mechanisms underlying these associations. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we examined prospective associations between DNA methylation (DNAm: nbirth = 804, nage 7 = 877) and trajectories of social communication deficits at age 8–17 years. Methylomic variation at three loci across the genome (false discovery rate = 0.048) differentiated children following high (n = 80) versus low (n = 724) trajectories of social communication deficits. This differential DNAm was specific to the neonatal period and not observed at 7 years of age. Associations between DNAm and trajectory membership remained robust after controlling for co-occurring mental health problems (i.e., hyperactivity/inattention, conduct problems). The three loci identified at birth were not replicated in the Generation R Study. However, to the best of our knowledge, ALSPAC is the only study to date that is prospective enough to examine DNAm in relation to longitudinal trajectories of social communication deficits from childhood to adolescence. Although the present findings might point to potentially novel sites that differentiate between a high versus low trajectory of social communication deficits, the results should be considered tentative until further replicated.

Violence exposure during childhood and adolescence is associated with a range of negative psychosocial outcomes. Research examining the impact of violence exposure has been limited by the compartmentalization into separate bodies of research (e.g., community violence, domestic violence). There is also a paucity of research examining long-term adult outcomes. Using a large and racially diverse sample (n = 754; male = 58%; Black = 46%), the current longitudinal study aimed to elucidate the comparative and cumulative effect of different types of violence exposure (witnessing vs. victimization) across different locations (home, school, neighborhood) in childhood and adolescence (lifetime through Grade 8) on long-term internalizing, externalizing, and attention problems; substance use; and intimate partner violence in adulthood (age 25). Victimization, but not witnessing violence, predicted all five adult outcomes. Specifically, being victimized at home was associated with the widest range of negative outcomes (internalizing, externalizing, and attention problems), while school victimization was associated with substance use. Further, when youth experienced multiple types of violence across multiple locations (cumulative violence exposure), they experienced a more diverse range of negative outcomes in adulthood (composite score). The current study highlights the stronger effects of violence exposure in more proximal contexts, and how these locations are important for emotional and behavioral development.

Although it is well known that parental depression is transmitted within families across generations, the etiology of this transmission remains unclear. Our goal was to develop a novel study design capable of explicitly examining the etiologic sources of intergenerational transmission. We specifically leveraged naturally-occurring variations in genetic relatedness between parents and their adolescent children in the 720 families participating in the Nonshared Environment in Adolescent Development (NEAD) study, 58.5% of which included a rearing stepparent (nearly always a stepfather). Results pointed squarely to the environmental transmission of psychopathology between fathers and children. Paternal depression was associated with adolescent depression and adolescent behavior problems (i.e., antisocial behavior, headstrong behavior, and attention problems) regardless of whether or not fathers and their children were genetically related. Moreover, these associations persisted to a subset of “blended” families in which the father was biologically related to one participating child but not to the other, and appeared to be mediated via father–child conflict. Such findings are not only fully consistent with the environmental transmission of psychopathology across generations, but also add to extant evidence that parent–child conflict is a robust and at least partially environmental predictor of adolescent psychopathology.

Stress has been linked with children’s socioemotional problems and lower language scores, particularly among children raised in socioeconomically disadvantaged circumstances. Much of the work examining the relations among stress, language, and socioemotional functioning have relied on assessments of a single dimension of maternal stress. However, stress can stem from different sources, and people may appraise stressors differently. Taking a dimensional approach, this manuscript characterizes stress in multiple ways: as an overall composite; across the constructs of psychological appraisal vs. environmental stressors; and the independent contributions of a variety assessments. Data are from 548 mother–infant dyads (M = 13.14 months, SD = 2.11) who served as the control group for a poverty reduction clinical trial. Mothers completed questionnaires regarding the different types of stresses they may have experienced, as well as their children’s language and socioemotional development. Results indicate that, collectively, higher maternal report of stress is associated with lower reports of children’s socioemotional and language development. In addition, maternal psychological appraisals of stress were associated with both socioemotional and language development, whereas reports of environmental stressors were only associated with socioemotional development. Together, these findings suggest that maternal reports of stress are associated with lower maternal report of child development among low-income children.

DNA methylation of the elongation of very long chain fatty acids protein 2 (ELOVL2) was suggested as a biomarker of biological aging, while childhood maltreatment (CM) has been associated with accelerated biological aging. We investigated the association of age and CM experiences with ELOVL2 methylation in peripheral blood mononuclear cells (PBMC). Furthermore, we investigated ELOVL2 methylation in the umbilical cord blood mononuclear cells (UBMC) of newborns of mothers with and without CM. PBMC and UBMC were isolated from 113 mother–newborn dyads and genomic DNA was extracted. Mothers with and without CM experiences were recruited directly postpartum. Mass array spectrometry and pyrosequencing were used for methylation analyses of ELOVL2 intron 1, and exon 1 and 5′ end, respectively. ELOVL2 5′ end and intron 1 methylation increased with higher age but were not associated with CM experiences. On the contrary, overall ELOVL2 exon 1 methylation increased with higher CM, but these changes were minimal and did not increase with age. Maternal CM experiences and neonatal methylation of ELOVL2 intron 1 or exon 1 were not significantly correlated. Our study suggests region-specific effects of chronological age and experienced CM on ELOVL2 methylation and shows that the epigenetic biomarker for age within the ELOVL2 gene does not show accelerated biological aging years after CM exposure.

School victimization has been negatively associated with children's social status. However, previous studies have primarily focused on peer victimization, leaving a significant knowledge gap regarding violence by teachers. We hypothesized that, when almost all children experience violence by teachers, not only the experience of violence, but also other factors, for example, mental health problems, may influence children's social preference and centrality. We therefore examined potential moderation effects of children's internalizing and externalizing problems. We implemented a multistage cluster randomized sampling approach to randomly chose fifth- and sixth-grade students from primary schools throughout Tanzania. Using a multi-informant approach, data were collected from 643 children (51.0% girls, Mage = 12.79 years). Results showed inconsistent direct associations between teacher violence and social status, whereas mental health problems were consistently associated with lower social status. Significant interaction effects were found for internalizing problems; that is, teacher violence was associated with lower social status for increasing internalizing problems. However, no interaction effects were found for externalizing problems. The findings underline the burden of exposure to violence by teachers and the importance of mental health for children's social functioning. Knowledge about interrelations can be applied in interventions to effectively reduce violence by teachers toward students.

Research in postconflict settings indicated that children's exposure to war and natural disaster is a significant predictor of experiencing violence within their families. However, it is unclear if this effect is driven by characteristics of traumatized children or their parents. To disentangle these different factors we conducted a survey in a children's home in Sri Lanka. A total of 146 institutionalized children (aged 8 to 17) were interviewed using standardized questionnaires administered by local senior counselors in order to assess children's exposure to mass trauma, family violence, and violence in the institution as well as their mental health. Linear regression analyses revealed that, controlling for potential confounds, previous exposure to civil war was a significant predictor of violence by guardians in the children's home. In addition, previous exposure to family violence was a significant predictor of violence by peers in the institutions. A mediation analysis showed that children's internalizing and externalizing behavior problems partly mediated the relationship between violence prior to the admission to the children's home and violence in the children's home. The findings of our study provide evidence for the assumption that the transmission of mass trauma into interpersonal violence can occur independently from parents through children's psychopathology.

The present study examined the intergenerational transmission of internalizing and externalizing symptom severity, which indexes comorbidity, and symptom directionality, which indicates differentiation toward externalizing versus internalizing problems. Data are from 854 male and female, same-sex adult twin pairs born between 1926 and 1971 (32–60 years old, M = 44.9 years, SD = 4.9 years) from the Twin and Offspring Study in Sweden and their adolescent offspring (11–22 years old, M = 15.7 years, SD = 2.4 years, 52% female). Children-of-twins models revealed additive (9%) and dominant (45%) genetic and nonshared environmental (47%) influences on twins’ symptom severity, and additive genetic (39%) and nonshared environmental (61%) influences on twins’ symptom directionality. Both comorbid problems and preponderance of symptoms of a particular – internalizing versus externalizing – spectrum were correlated across parent and child generations, although associations were modest especially for directionality (i.e., transmission of specific symptom type). By interpreting findings alongside a recent study of adolescent twins, we demonstrate that the intergenerational transmission of symptom severity and symptom directionality are both unlikely to be attributable to genetic transmission, are both likely to be influenced by direct phenotypic transmission and/or nonpassive rGE, and the intergenerational transmission of symptom severity is also likely to be influenced by passive rGE.

Sports participation, physical activity, and friendship quality are theorized to have protective effects on the developmental emergence of substance use and self-harm behavior in adolescence, but existing research has been mixed. This ambiguity could reflect, in part, the potential for confounding of observed associations by genetic and environmental factors, which previous research has been unable to rigorously rule out. We used data from the prospective, population-based Child and Adolescent Twin Study in Sweden (n = 18,234 born 1994–2001) and applied a co-twin control design to account for potential genetic and environmental confounding of sports participation, physical activity, and friendship quality (assessed at age 15) as presumed protective factors for adolescent substance use and self-harm behavior (assessed at age 18). While confidence intervals widened to include the null in numerous co-twin control analyses adjusting for childhood psychopathology, parent-reported sports participation and twin-reported positive friendship quality were associated with increased odds of alcohol problems and nicotine use. However, parent-reported sports participation, twin-reported physical activity, and twin-reported friendship quality were associated with decreased odds of self-harm behavior. The findings provide a more nuanced understanding of the risks and benefits of putative protective factors for risky behaviors that emerge during adolescence.

Exposure to chronic early trauma carries lasting effects on children's well-being and adaptation. Guided by models on resilience, we assessed the interplay of biological, emotional, cognitive, and relational factors in shaping two regulatory outcomes in trauma-exposed youth: emotion recognition (ER) and executive functions (EF). A unique war-exposed cohort was followed from early childhood to early adolescence. At preadolescence (11–13 years), ER and EF were assessed and respiratory sinus arrhythmia (RSA), biomarker of parasympathetic regulation, was quantified. Mother–child dyadic reciprocity, child's avoidance symptoms, and cortisol (CT) were measured in early childhood. Trauma-exposed youth displayed impaired ER and EF abilities. Conditional process analysis described two differential indirect paths leading from early trauma to regulatory outcomes. ER was mediated by avoidance symptoms in early childhood and modulated by cortisol, such that this path was evident only for preadolescents with high, but not low, CT. In comparison, EF was mediated by the degree of dyadic reciprocity experienced in early childhood and modulated by RSA, observed only among youth with lower RSA. Findings pinpoint trauma-related disruptions to key regulatory support systems in preadolescence as mediated by early-childhood relational, clinical, and physiological factors and highlight the need to specify biobehavioral precursors of resilience toward targeted early interventions.

Being able to control oneself in emotionally upsetting situations is essential for good relationship functioning. According to life history theory, childhood exposure to harshness and unpredictability should forecast diminished emotional control and lower relationship quality. We examined this in three studies. In Studies 1 and 2, greater childhood unpredictability (frequent financial, residential, and familial changes), but not harshness (low SES), was associated with lower emotional control in adolescents (N = 1041) and adults (N = 327). These effects were stronger during the participants’ reproductive years. Moreover, in Study 2, greater childhood unpredictability was indirectly associated with lower relationship quality through lower emotional control. In study 3, we leveraged the Minnesota Longitudinal Study of Risk and Adaptation (N = 160). Greater early-life unpredictability (ages 0–4) prospectively predicted lower relationship quality at age 32 via lower emotional control at the same age. This relation was serially mediated by less supportive observed early maternal care (ages 1.5–3.5) and insecure attachment representations (ages 19 and 26). Early unpredictability also predicted greater observed emotional distress during conflict interactions with romantic partners (ages 19–36). These findings point to the role of emotional control in mediating the effects of unpredictable childhood environments on relationship functioning in adulthood.

Child sexual abuse (CSA) is a notable risk factor for depressive disorders. Though multiply determined, increased sensitivity to stress (stress sensitization) and difficulty managing distress (emotion regulation) may reflect two pathways by which CSA confers depression risk. However, it remains unclear whether stress sensitization and emotion regulation deficits contribute to depression risk independently or in a sequential manner. That is, the frequent use of maladaptive emotion regulation responses and insufficient use of those that attenuate distress (adaptive emotion regulation) may lead to stress sensitization. We tested competing models of CSA, stress sensitization, and emotion regulation to predict depression symptoms and depressive affects in daily life among adults with and without histories of CSA. Results supported a sequential mediation: CSA predicted greater maladaptive repertoires that, in turn, exacerbated the effects of stress on depression symptoms. Maladaptive responses also exacerbated the effects of daily life stress on contemporaneous negative affect (NA) levels and their increase over time. Independent of stress sensitization, emotion regulation deficits also mediated CSA effects on both depressive outcomes, though the effect of maladaptive strategies was specific to NA, and adaptive responses to positive affect. Our findings suggest that emotion regulation deficits and stress sensitization play key intervening roles between CSA and risk for depression.

This study evaluated whether children with higher adverse childhood experiences (ACE) scores had alterations in immune cell gene expression profiles. RNA sequencing was conducted on dried blood spot samples from 37 generally healthy English-speaking children (age 5–11) who were recruited from well-child visits at a university-affiliated pediatric practice. The Whole Child Assessment was used to assess ACE exposure. Primary analyses examined an a priori-specified composite of 19 pro-inflammatory gene transcripts. Secondary analyses examined a 34-gene composite assessing Type I interferon response, and used Transcript Origin Analyses to identify cellular mechanisms. After controlling for age, body mass index percentile, sex, race/ethnicity, current insurance status, and household smoking exposure, pro-inflammatory gene expression was elevated by 0.094 log2 RNA expression units with each Child-ACE total score point (p = .019). Type I interferon gene expression was similarly upregulated (0.103; p = .008). Transcript origin analyses implicated CD8+ T cell as the primary sources of gene transcripts upregulated, and nonclassical (CD16+) monocytes as sources of downregulated transcripts. These preliminary analyses suggest that parent-reported ACE exposures are associated with increased expression of both inflammatory and interferon gene transcripts in children's circulating blood cells.

Aggressive behavior in middle childhood can contribute to peer rejection, subsequently increasing risk for substance use in adolescence. However, the quality of peer relationships a child experiences can be associated with his or her genetic predisposition, a genotype–environment correlation (rGE). In addition, recent evidence indicates that psychosocial preventive interventions can buffer genetic predispositions for negative behavior. The current study examined associations between polygenic risk for aggression, aggressive behavior, and peer rejection from 8.5 to 10.5 years, and the subsequent influence of peer rejection on marijuana use in adolescence (n = 515; 256 control, 259 intervention). Associations were examined separately in control and intervention groups for children of families who participated in a randomized controlled trial of the family-based preventive intervention, the Family Check-Up . Using time-varying effect modeling (TVEM), polygenic risk for aggression was associated with peer rejection from approximately age 8.50 to 9.50 in the control group but no associations were present in the intervention group. Subsequent analyses showed peer rejection mediated the association between polygenic risk for aggression and adolescent marijuana use in the control group. The role of rGEs in middle childhood peer processes and implications for preventive intervention programs for adolescent substance use are discussed.

This research examines maternal smoking during pregnancy and risk for poorer executive function in siblings discordant for exposure. Data (N = 173 families) were drawn from the Missouri Mothers and Their Children study, a sample, identified using birth records (years 1998–2005), in which mothers changed smoking behavior between two pregnancies (Child 1 [older sibling]: Mage = 12.99; Child 2 [younger sibling]: Mage = 10.19). A sibling comparison approach was used, providing a robust test for the association between maternal smoking during pregnancy and different aspects of executive function in early-mid adolescence. Results suggested within-family (i.e., potentially causal) associations between maternal smoking during pregnancy and one working memory task (visual working memory) and one response inhibition task (color-word interference), with increased exposure associated with decreased performance. Maternal smoking during pregnancy was not associated with stop-signal reaction time, cognitive flexibility/set-shifting, or auditory working memory. Initial within-family associations between maternal smoking during pregnancy and visual working memory as well as color-word interference were fully attenuated in a model including child and familial covariates. These findings indicate that exposure to maternal smoking during pregnancy may be associated with poorer performance on some, but not all skills assessed; however, familial transmission of risk for low executive function appears more important.

Early psychosocial adversities exist at many levels, including caregiving-related, extrafamilial, and sociodemographic, which despite their high interrelatedness may have unique impacts on development. In this paper, we focus on caregiving-related early adversities (crEAs) and parse the heterogeneity of crEAs via data reduction techniques that identify experiential cooccurrences. Using network science, we characterized crEA cooccurrences to represent the comorbidity of crEA experiences across a sample of school-age children (n = 258; 6–12 years old) with a history of crEAs. crEA dimensions (variable level) and crEA subtypes (subject level) were identified using parallel factor analysis/principal component analysis and graph-based Louvain community detection. Bagging enhancement with cross-validation provided estimates of robustness. These data-driven dimensions/subtypes showed evidence of stability, transcended traditional sociolegally defined groups, were more homogenous than sociolegally defined groups, and reduced statistical correlations with sociodemographic factors. Finally, random forests showed both unique and common predictive importance of the crEA dimensions/subtypes for childhood mental health symptoms and academic skills. These data-driven outcomes provide additional tools and recommendations for crEA data reduction to inform precision medicine efforts in this area.

The aim of this project was to evaluate the relationship of matrix metalloproteinase-9 (MMP-9) genetic variation and its serum concentration with autism spectrum disorder (ASD). One hundred ASD and 120 controls were enrolled in this study. Genomic DNA was extracted from blood and MMP-9 polymorphism was determined by polymerase chain reaction restriction fragment length polymorphism and serum levels were measured by enzyme-linked immunosorbent assay. The frequencies of CC, CT, and TT genotypes were 72%, 26%, and 2% in controls and 31%, 57%, and 12% in ASD, respectively. The frequencies of C and T alleles in ASD were 59.5% and 40.5%, and controls were 86% and 14%, respectively. There is a significant increase in serum MMP-9 levels in ASD as compared to controls. We have also shown that TT genotype is significantly associated with increase serum MMP-9 levels in patients (TT, CT, and CC serum levels were 91.77 ± 10.53, 70.66 ± 7.21, and 38.66 ± 5.52 and in controls were 55.55 ± 11.39, 42.66 ± 7.85, and 30.55 ± 6.34 ng/ml, respectively). It is concluded that there is a significant association between rs3918242 MMP-9 polymorphism and its serum concentration with autism. We also suggest that TT genotype is associated with increased MMP9 expression and may be a risk factor for ASD.

Positive health endpoints are not the opposite of negative endpoints. Previous studies examining posttraumatic stress disorders (PTSD) and posttraumatic growth (PTG) trajectories have overlooked the co-existence of PTSD and PTG, making it difficult to accurately distinguish individuals with various posttraumatic presentations, causing the effects of targeted interventions to be discounted. To fill this gap, the current study sought to examine joint PTSD and PTG trajectories in children and adolescents. Eight hundred and seventy-six Chinese children and adolescents were recruited to complete self-report questionnaires 6, 12, and 18 months after the Ya'an earthquake. Multiple-process growth mixture modeling analysis was used to test the study proposal. Five distinct joint PTSD and PTG trajectory types were found: recovery, growth, struggling, resistant, and delayed symptoms. Female students and students who felt trapped or fearful were more likely to be in the struggling group, and students who experienced injury to themselves or family members were more likely to belong to the delayed symptom group. These findings suggest that postdisaster psychological services should be provided to relieve delayed symptoms in individuals who experience injury to themselves or their family members, and individuals in the struggling group should be supported to achieve growth.