The current study examined whether consistency in day-to-day interactions between children and parents related to inflammatory cytokine production in youths. One hundred twenty-three parents recorded the daily quality of interactions and timing of leisure activities with their adolescent children for 2 weeks, and the degree of variability in those ratings was calculated. One year later, the production of proinflammatory cytokines in youths’ blood was measured in response to in vitro exposure to lipopolysaccharide (a bacterial product). The results indicate that greater variability in parent–child relationship quality related to greater stimulated proinflammatory cytokine production in youths, above and beyond overall relationship quality. Greater variability in the timing of parent–child leisure activities also predicted greater stimulated proinflammatory cytokine production in youths, regardless of the frequency of interactions. In sum, consistency in both the affective and temporal aspects of parent–child relationships may contribute to inflammatory processes in youth.

Early-onset conduct problems (CP) are a key predictor of adult criminality and poor mental health. While previous studies suggest that both genetic and environmental risks play an important role in the development of early-onset CP, little is known about potential biological processes underlying these associations. In this study, we examined prospective associations between DNA methylation (cord blood at birth) and trajectories of CP (4–13 years), using data drawn from the Avon Longitudinal Study of Parents and Children. Methylomic variation at seven loci across the genome (false discovery rate < 0.05) differentiated children who go on to develop early-onset (n = 174) versus low (n = 86) CP, including sites in the vicinity of the monoglyceride lipase (MGLL) gene (involved in endocannabinoid signaling and pain perception). Subthreshold associations in the vicinity of three candidate genes for CP (monoamine oxidase A [MAOA], brain-derived neurotrophic factor [BDNF], and FK506 binding protein 5 [FKBP5]) were also identified. Within the early-onset CP group, methylation levels of the identified sites did not distinguish children who will go on to persist versus desist in CP behavior over time. Overall, we found that several of the identified sites correlated with prenatal exposures, and none were linked to known genetic methylation quantitative trait loci. Findings contribute to a better understanding of epigenetic patterns associated with early-onset CP.

In a large-scale (N = 317) prospective 8-year longitudinal multiage, multidomain, multivariate, multisource study, we tested a conservative three-term model linking parenting cognitions in toddlerhood to parenting practices in preschool to classroom externalizing behavior in middle childhood, controlling for earlier parenting practices and child externalizing behavior. Mothers who were more knowledgeable, satisfied, and attributed successes in their parenting to themselves when their toddlers were 20 months of age engaged in increased supportive parenting during joint activity tasks 2 years later when their children were 4 years of age, and 6 years after that their 10-year-olds were rated by teachers as having fewer classroom externalizing behavior problems. This developmental cascade of a “standard model” of parenting applied equally to families with girls and boys, and the cascade from parenting attributions to supportive parenting to child externalizing behavior obtained independent of 12 child, parent, and family covariates. Conceptualizing socialization in terms of cascades helps to identify points of effective intervention.

Emerging developmental perspectives suggest that adverse rearing environments promote neurocognitive adaptations that heighten impulsivity and increase vulnerability to risky behavior. Although studies document links between harsh rearing environments and impulsive behavior on substance use, the developmental hypothesis that impulsivity acts as mechanism linking adverse rearing environments to downstream substance use remains to be investigated. The present study investigated the role of impulsivity in linking child abuse and neglect with adult substance use using data from (a) a longitudinal sample of youth (Study 1, N = 9,421) and (b) a cross-sectional sample of adults (Study 2, N = 1,011). In Study 1, the links between child abuse and neglect and young adult smoking and marijuana use were mediated by increases in adolescent impulsivity. In Study 2, indirect links between child abuse and neglect and substance use were evidenced via delayed reward discounting and impulsivity traits. Among impulsivity subcomponents, robust indirect effects connecting childhood experiences to cigarette use emerged for negative urgency. Negative urgency, positive urgency, and sensation seeking mediated the effect of child abuse and neglect on cannabis and alcohol use. Results suggest that child abuse and neglect increases risk for substance use in part, due to effects on impulsivity. Individuals with adverse childhood experiences may benefit from substance use preventive intervention programs that target impulsive behaviors.

The Dysregulation Profile (DP) is a broad indicator of concurrent affective, behavioral, and cognitive dysregulation, often measured with the anxious/depressed, aggressive behavior, and attention problems syndrome scales of the Child Behavior Checklist. Despite an expanding body of research on the DP, knowledge of the normative developmental course of the DP from early childhood to adolescence is lacking. Furthermore, although we know that the DP longitudinally predicts personality pathology, no research yet has examined whether next to the DP in early childhood, the rate of change of the DP across development predicts personality pathology. Therefore, using cohort-sequential latent growth modeling in a population-based sample (N = 668), we examined the normative developmental course of mother-reported DP from ages 4 to 17 years and its associations with a wide range of adolescent-reported personality pathology dimensions 3 years later. The results showed that the DP follows a nonlinear developmental course with a peak in early adolescence. The initial level of the DP at age 4 and, to a lesser extent, the rate of change in the DP predicted a range of personality pathology dimensions in late adolescence. The findings suggest that the DP is a broad developmental precursor of personality pathology in late adolescence.

Social anxiety is one of the most commonly reported mental health problems among adolescents, and it has been suggested that parenting style influences an adolescent's level of anxiety. A context-dependent effect of oxytocin on human social behavior has been proposed; however, research on the oxytocin gene (OXT) has mostly been reported without considering contextual factors. This study investigated the interactions between parenting style and polymorphic variations in the OXT gene in association with social anxiety symptoms in a community sample of adolescents (n = 1,359). Two single nucleotide polymorphisms linked to OXT, rs4813625 and rs2770378, were genotyped. Social anxiety and perceived parenting style were assessed by behavioral questionnaires. In interaction models adjusted for sex, significant interaction effects with parenting style were observed for both variants in relation to social anxiety. The nature of the interactions was in line with the differential susceptibility framework for rs4813625, whereas for rs2770378 the results indicated a diathesis–stress type of interaction. The findings may be interpreted from the perspective of the social salience hypothesis of oxytocin, with rs4813625 affecting social anxiety levels along a perceived unsafe–safe social context dimension.

The codevelopment of symptoms of depression and socially prescribed perfectionism across adolescence (age 12–17) and non–age-overlapping childhood predictors (age 10–11) of joint trajectory group membership were examined in a sample of 700 Canadian youth. Results indicated that most adolescents (75.8%) followed a trajectory of low depression symptoms (low stable), whereas 15.7% followed an increasing trajectory (increasing), and 8.5% followed a trajectory that began high and decreased over time (high decreasing). More girls than boys were found in the increasing and high decreasing depression trajectories. Adolescents followed three distinct trajectories of socially prescribed perfectionism: 41.6% were in a low stable group, 40.5% in a moderate increasing group, and 17.9% in a high increasing group. Eight percent followed a high-risk dual trajectory of increasing depression and high increasing socially prescribed perfectionism. This joint trajectory was predicted by being bullied, anxious, and relationally aggressive (compared to the low-risk trajectory of low stable depression and perfectionism) at ages 10 and 11. These same predictors, along with poorer family functioning and lower family income, differentiated the joint high decreasing depression/high increasing perfectionism group from the low/low joint group, which comprised of 3.8% of the sample. The developmental progression was best characterized as depression leading to socially prescribed perfectionism. Implications for clinical practice are discussed.

By definition, autism spectrum disorder (ASD) is a neurodevelopmental disorder that emerges during early childhood. It is during this time that infants and toddlers transition from appearing typical across multiple domains to exhibiting the behavioral phenotype of ASD. Neuroimaging studies focused on this period of development have provided crucial knowledge pertaining to this process, including possible mechanisms underlying pathogenesis of the disorder and offering the possibility of prodromal or presymptomatic prediction of risk. In this paper, we review findings from structural and functional brain imaging studies of ASD focused on the first years of life and discuss implications for next steps in research and clinical applications.

We examined associations between specific self-regulatory mechanisms and externalizing behavior patterns from ages 2 to 15 (N = 443). The relation between multiple self-regulatory indicators across multiple domains (i.e., physiological, attentional, emotional, and behavioral) at age 2 and at age 5 and group membership in four distinct externalizing trajectories was examined. By examining each of these self-regulatory processes in combination with one another, and therefore accounting for their shared variance, we aimed to better understand which specific self-regulatory skills were associated most strongly with externalizing behavioral patterns. Findings suggest that behavioral inhibitory control and emotion regulation are particularly important in distinguishing between children who show normative declines in externalizing behaviors across early childhood and those who demonstrate high levels through adolescence.

Several studies have suggested that the neuropeptide oxytocin may enhance aspects of social communication in autism. Little is known, however, about its effects on nonsocial manifestations, such as restricted interests and repetitive behaviors. In the empathizing–systemizing theory of autism, social deficits are described along the continuum of empathizing ability, whereas nonsocial aspects are characterized in terms of an increased preference for patterned or rule-based systems, called systemizing. We therefore developed an automated eye-tracking task to test whether children and adolescents with autism spectrum disorder (ASD) compared to matched controls display a visual preference for more highly organized and structured (systemized) real-life images. Then, as part of a randomized, double-blind, placebo-controlled crossover study, we examined the effect of intranasal oxytocin on systemizing preferences in 16 male children with ASD, compared with 16 matched controls. Participants viewed 14 slides, each containing four related pictures (e.g., of people, animals, scenes, or objects) that differed primarily on the degree of systemizing. Visual systemizing preference was defined in terms of the fixation time and count for each image. Unlike control subjects who showed no gaze preference, individuals with ASD preferred to fixate on more highly systemized pictures. Intranasal oxytocin eliminated this preference in ASD participants, who now showed a similar response to control subjects on placebo. In contrast, control participants increased their visual preference for more systemized images after receiving oxytocin versus placebo. These results suggest that, in addition to its effects on social communication, oxytocin may play a role in some of the nonsocial manifestations of autism.

We present a developmental cascade model of the longitudinal relationships between internalizing symptoms, externalizing problems, and academic performance in middle childhood, utilizing a large sample (N = 1,771) from the United Kingdom in a 3-year, cross-lag design. Three hypotheses were tested: adjustment erosion, academic incompetence, and (cumulative) shared risk. In addition, we sought to examine whether developmental cascade pathways varied across gender, while also statistically exploring indirect, mediation pathways. Structural equation models that accounted for within-time covariance, data nesting, and temporal stability provided evidence of gender-specific effects as follows: externalizing-attainment adjustment erosion pathways were found only in boys, while attainment-internalizing/externalizing academic incompetence pathways were found only in girls. Analysis of mediation pathways provided further support for these gender-specific longitudinal profiles. Protective longitudinal internalizing-externalizing and externalizing-internalizing pathways were found for both boys and girls. Finally, while it improved model fit for both genders, the influence of cumulative shared risk on the aforementioned pathways was relatively meager, substantively affecting only one (externalizing-attainment adjustment erosion pathway in boys). The implications of these findings are discussed, and study limitations noted.

Experiencing maltreatment during childhood can have long-lasting consequences for both mental and physical health. Immune cell telomere length (TL) shortening might be one link between child maltreatment (CM) experiences and adverse health outcomes later in life. While the stress hormone cortisol has been associated with TL attrition, the attachment-related hormone oxytocin may promote resilience. In 15 mothers with and 15 age- and body mass index-matched mothers without CM, we assessed TL in peripheral blood mononuclear cells and selected immune cell subsets (monocytes, naive, and memory cytotoxic T cells) by quantitative fluorescence in situ hybridization, as well as peripheral cortisol and oxytocin levels. Memory cytotoxic T cells showed significantly shorter TL in association with CM, whereas TL in monocytes and naive cytotoxic T cells did not significantly differ between the two groups. Across both groups, cortisol was negatively associated with TL, while oxytocin was positively associated with TL in memory cytotoxic T cells. These results indicate that long-lived memory cytotoxic T cells are most affected by the increased biological stress state associated with CM. Keeping in mind the correlational and preliminary nature of the results, the data suggest that cortisol may have a damaging and oxytocin a protective function on TL.

A common theory of autism spectrum disorder (ASD) symptom onset includes toddlers who do not display symptoms until well after age 2, which are termed late-onset ASD cases. Objectives were to analyze differences in clinical phenotype between toddlers identified as ASD at initial evaluations (early diagnosed) versus those initially considered nonspectrum, then later identified as ASD (late diagnosed). Two hundred seventy-three toddlers recruited from the general population based on a failed developmental screening form or parent or physician concerns were followed longitudinally from 12 months and identified as early- and late-diagnosed cases of ASD, language delayed, or typically developing. Toddlers completed common standardized assessments and experimental eye-tracking and observational measures every 9–12 months until age 3. Longitudinal performance on standardized assessments and experimental tests from initial evaluations were compared. Delay in social communication skills was seen in both ASD groups at early-age initial assessment, including increased preference for nonsocial stimuli, increased stereotypic play, reduced exploration, and use of gestures. On standardized psychometric assessments, early-diagnosed toddlers showed more impairment initially while late-diagnosed toddlers showed a slowing in language acquisition. Similar social communication impairments were present at very early ages in both early-detected ASD and so-called late-onset ASD. Data indicate ASD is present whether detected or not by current methods, and development of more sensitive tools is needed.

Severe temper outbursts (STO) in children are associated with impaired school and family functioning and may contribute to negative outcomes. These outbursts can be conceptualized as excessive frustration responses reflecting reduced emotion regulation capacity. The anterior cingulate cortex (ACC) has been implicated in negative affect as well as emotional control, and exhibits disrupted function in children with elevated irritability and outbursts. This study examined the intrinsic functional connectivity (iFC) of a region of the ACC, the anterior midcingulate cortex (aMCC), in 5- to 9-year-old children with STO (n = 20), comparing them to children with attention-deficit/hyperactivity disorder (ADHD) without outbursts (ADHD; n = 18). Additional analyses compared results to a sample of healthy children (HC; n = 18) and examined specific associations with behavioral and emotional dysregulation. Compared to the ADHD group, STO children exhibited reduced iFC between the aMCC and surrounding regions of the ACC, and increased iFC between the aMCC and precuneus. These differences were also seen between the STO and HC groups; ADHD and HC groups did not differ. Specificity analyses found associations between aMCC–ACC connectivity and hyperactivity, and between aMCC–precuneus iFC and emotion dysregulation. Disruption in aMCC networks may underlie the behavioral and emotional dysregulation characteristic of children with STO.

Although infants less than 18 months old are capable of engaging in self-regulatory behavior (e.g., avoidance, withdrawal, and orienting to other aspects of their environment), the use of self-regulatory strategies at this age (as opposed to relying on caregivers) is associated with elevated behavioral and physiological distress. This study investigated infant dopamine-related genotypes (dopamine receptor D2 [DRD2], dopamine transporter solute carrier family C6, member 4 [SLC6A3], and catechol-O-methyltransferase [COMT]) as they interact with maternal self-reported history of maltreatment to predict observed infant independent emotion regulation behavior. A community sample (N = 193) of mother–infant dyads participated in a toy frustration challenge at infant age 15 months, and infant emotion regulation behavior was coded. Buccal cells were collected for genotyping. Maternal maltreatment history significantly interacted with infant SLC6A3 and COMT genotypes, such that infants with more 10-repeat and valine alleles of SLC6A3 and COMT, respectively, relative to infants with fewer or no 10-repeat and valine alleles, utilized more independent (i.e., maladaptive) regulatory behavior if mother reported a more extensive maltreatment history, as opposed to less. The findings indicate that child genetic factors moderate the intergenerational impact of maternal maltreatment history. The results are discussed in terms of potential mechanism of Gene × Environment interaction.

The current study advanced research on the link between community violence exposure and aggression by comparing the effects of violence exposure on different functions of aggression and by testing four potential (i.e., callous–unemotional traits, consideration of others, impulse control, and anxiety) mediators of this relationship. Analyses were conducted in an ethnically/racially diverse sample of 1,216 male first-time juvenile offenders (M = 15.30 years, SD = 1.29). Our results indicated that violence exposure had direct effects on both proactive and reactive aggression 18 months later. The predictive link of violence exposure to proactive aggression was no longer significant after controlling for proactive aggression at baseline and the overlap with reactive aggression. In contrast, violence exposure predicted later reactive aggression even after controlling for baseline reactive aggression and the overlap with proactive aggression. Mediation analyses of the association between violence exposure and reactive aggression indicated indirect effects through all potential mediators, but the strongest indirect effect was through impulse control. The findings help to advance knowledge on the consequences of community violence exposure on justice-involved youth.

In this study, we used a stress test to investigate endocrinological and subjective stress responses of 8- to 14-year-old children with internalizing or externalizing disorders and healthy controls. The sample (N = 170) consisted of clinical and community children. Parents were given a diagnostic interview to diagnose their children's psychiatric condition. We measured saliva cortisol and subjectively experienced arousal in children before and after the Trier Social Stress Test for Children. Children also rated their performance immediately after the stress test, and 1 hr later they rated their positive and negative thoughts about this stressful event. Children with internalizing or externalizing disorders exhibited a blunted cortisol response compared to healthy controls. Depressed children rated their test performance lower and reported more negative thoughts after the test in comparison to healthy controls, anxious children reported more arousal before and after the task, and children with externalizing disorders reported more positive thoughts. In regression analyses, cortisol and subjective stress responses were both predictive of psychiatric disorders. The study extends previous work on the relation between psychiatric disorders and children's stress responses to an experimentally induced stress task by including a broad range of psychiatric disorders and by integrating endocrinological and subjective stress responses.

A growing number of research studies have examined the intradyadic coregulation (or attunement) of hypothalamus–pituitary–adrenal axis functioning in mothers and their children. However, it is unclear how early this coregulation may be present in dyads at clinical high risk and whether certain factors, such as maternal depression or positive parenting, are associated with the strength of this coregulation. The present study examined cortisol attunement within mother–infant dyads in a high-risk sample of 233 mothers who received treatment for psychiatric illness during pregnancy and whose infants were 6 months old at the study visit. Results showed that maternal and infant cortisol covaried across four time points that included a stressor paradigm and a mother–infant interaction task. Greater maternal positive affect, but not depression, predicted stronger cortisol attunement. In addition, infants’ cortisol level following separation from the mother predicted mothers’ cortisol level at the next time point. Mothers’ cortisol level following the separation and the laboratory stress paradigm predicted infants’ cortisol levels at each successive time point, over and above infants’ own cortisol at the previous time point. These findings suggest that maternal and infant cortisol levels influence one another in a bidirectional fashion that may be temporally and context dependent.

The offspring of parents with bipolar disorder (OBD) are at high risk for developing mental disorders. In addition to genetic factors, environmental risk is purported to be associated with these negative outcomes. However, few studies have examined this relation. Using concurrent and longitudinal data, we examined if support, structure, and control provided by parents in middle childhood mediated the relation between having a parent with or without bipolar disorder, and offspring mental health. The sample included 145 offspring (77 OBD, 68 controls) aged 4 to 14 years and their parents. Parent and teacher ratings of child behavior were collected, and diagnostic assessments were conducted in offspring 12 years later (n = 101). Bootstrapping analyses showed that low levels of structure mediated the relation between having a parent with bipolar disorder and elevated internalizing and externalizing difficulties during middle childhood. For the longitudinal outcomes, parental control emerged as the strongest mediator of the relation between parents’ bipolar disorder and offspring psychopathology. Suboptimal childrearing may have different immediate and enduring consequences on mental health outcomes in the OBD. Parental structure has robust effects on emotional and behavioral problems in middle childhood, while levels of control promote psychological adjustment in the OBD as they mature.

Maltreated children in foster care are at high risk for dysregulated hypothalamus–pituitary–adrenal (HPA) axis functioning and educational difficulties. The present study examined the effects of a short-term school readiness intervention on HPA axis functioning in response to the start of kindergarten, a critical transition marking entry to formal schooling, and whether altered HPA axis functioning influenced children's school adjustment. Compared to a foster care comparison group, children in the intervention group showed a steeper diurnal cortisol slope on the first day of school, a pattern previously observed among nonmaltreated children. A steeper first day of school diurnal cortisol slope predicted teacher ratings of better school adjustment (i.e., academic performance, appropriate classroom behaviors, and engagement in learning) in the fall of kindergarten. Furthermore, the children's HPA axis response to the start of school mediated the effect of the intervention on school adjustment. These findings support the potential for ameliorative effects of interventions targeting critical transitional periods, such as the transition of formal schooling. This school readiness intervention appears to influence stress neurobiology, which in turn facilitates positive engagement with the school environment and better school adjustment in children who have experienced significant early adversity.