Serotonin signaling pathways play a key role in brain development, stress reactivity, and mental health. Epigenetic alterations in the serotonin system may underlie the effect of early life stress on psychopathology. The current study examined methylation of the serotonin receptor 2A (HTR2A) gene in a sample of 228 children including 119 with child welfare documentation of moderate to severe maltreatment within the last 6 months. Child protection records, semistructured interviews in the home, and parent reports were used to assess child stress exposure, psychiatric symptoms, and behavior. The HTR2A genotype and methylation of HTR2A were measured at two CpG sites (–1420 and –1224) from saliva DNA. HTR2A genotype was associated with HTR2A methylation at both CpG sites. HTR2A genotype also moderated associations of contextual stress exposure and HTR2A methylation at site –1420. Contextual stress was positively associated with –1420 methylation among A homozygotes, but negatively associated with –1420 methylation among G homozygotes. Posttraumatic stress disorder and major depressive disorder symptoms were negatively associated with methylation at –1420, but positively associated with methylation at –1224. Results support the view that the serotonin system is sensitive to stress exposure and psychopathology, and HTR2A methylation may be a mechanism by which early adversity is biologically encoded.

Child maltreatment is known to engender negative emotional and behavioral consequences. Although neglect is the most frequent form of maltreatment, it has thus far only received little attention, especially when looking at low-resource countries. The current study investigated possible associations between neglect and internalizing and externalizing problems. As neglect and abuse often co-occur, the latter was controlled for. In total, 409 Tanzanian primary school students (52% boys, M = 10.5 years, range = 6–15) participated in the cross-sectional study. Structured clinical interviews were conducted assessing maltreatment, internalizing problems, and externalizing problems. Overall, 31% (n = 128) of the children reported at least one type of physical neglect and 31% (n = 127) of emotional neglect. Using structural equation modeling, we found a significant association between neglect and internalizing (β = 0.59, p < .01) and externalizing problems (β = 0.35, p < .05). However, these associations could only be detected in younger children (ages 6–9), whereas in older children (ages 10–15), mental health problems were significantly related to violence and abuse. Our findings suggest that the current age may influence the association between maltreatment type and the development of internalizing and/or externalizing problems.

While child poverty is a significant risk factor for poor mental health, the developmental pathways involved with these associations are poorly understood. To advance knowledge about these important linkages, the present study examined the developmental sequelae of childhood exposure to poverty in a multiyear longitudinal study. Here, we focused on exposure to poverty, neurobiological circuitry connected to emotion dysregulation, later exposure to stressful life events, and symptoms of psychopathology. We grounded our work in a biopsychosocial perspective, with a specific interest in “stress sensitization” and emotion dysregulation. Motivated by past work, we first tested whether exposure to poverty was related to changes in the resting-state coupling between two brain structures centrally involved with emotion processing and regulation (the amygdala and the ventromedial prefrontal cortex; vmPFC). As predicted, we found lower household income at age 10 was related to lower resting-state coupling between these areas at age 15. We then tested if variations in amygdala–vmPFC connectivity interacted with more contemporaneous stressors to predict challenges with mental health at age 16. In line with past reports showing risk for poor mental health is greatest in those exposed to early and then later, more contemporaneous stress, we predicted and found that lower vmPFC–amygdala coupling in the context of greater contemporaneous stress was related to higher levels of internalizing and externalizing symptoms. We believe these important interactions between neurobiology and life history are an additional vantage point for understanding risk and resiliency, and suggest avenues for prediction of psychopathology related to early life challenge.

We examined maternal depression and maternal sensitivity as mediators of the association between maternal childhood adversity and her child's temperament in 239 mother–child dyads from a longitudinal, birth cohort study. We used an integrated measure of maternal childhood adversity that included the Childhood Trauma Questionnaire and the Parental Bonding Index. Maternal depression was assessed with the Edinburgh Postnatal Depression Scale at 6 months postpartum. Maternal sensitivity was assessed with the Ainsworth maternal sensitivity scales at 6 months. A measure of “negative emotionality/behavioral dysregulation” was derived from the Early Childhood Behaviour Questionnaire administered at 36 months. Bootstrapping-based mediation analyses revealed that maternal depression mediated the effect of maternal childhood adversity on offspring negative emotionality/behavioral dysregulation (95% confidence interval [0.026, 0.144]). We also found a serial, indirect effect of maternal childhood adversity on child negative emotionality/behavioral mediated first by maternal depression and then by maternal sensitivity (95% confidence interval [0.031, 0.156]). Results suggest the intergenerational transmission of the effects of maternal childhood adversity to the offspring occurs through a two-step, serial pathway, involving maternal depression and maternal sensitivity.

We contribute to the literature on the relations of temperament to externalizing and internalizing problems by considering parental emotional expressivity and child gender as moderators of such relations and examining prediction of pure and co-occurring problem behaviors during early to middle adolescence using bifactor models (which provide unique and continuous factors for pure and co-occurring internalizing and externalizing problems). Parents and teachers reported on children's (4.5- to 8-year-olds; N = 214) and early adolescents’ (6 years later; N = 168) effortful control, impulsivity, anger, sadness, and problem behaviors. Parental emotional expressivity was measured observationally and with parents’ self-reports. Early-adolescents’ pure externalizing and co-occurring problems shared childhood and/or early-adolescent risk factors of low effortful control, high impulsivity, and high anger. Lower childhood and early-adolescent impulsivity and higher early-adolescent sadness predicted early-adolescents’ pure internalizing. Childhood positive parental emotional expressivity more consistently related to early-adolescents’ lower pure externalizing compared to co-occurring problems and pure internalizing. Lower effortful control predicted changes in externalizing (pure and co-occurring) over 6 years, but only when parental positive expressivity was low. Higher impulsivity predicted co-occurring problems only for boys. Findings highlight the probable complex developmental pathways to adolescent pure and co-occurring externalizing and internalizing problems.

Children who participate in the Mother-Child Project, a longitudinal study of high-risk children, were giver projective storytelling task during their sixth-grade year. Story sets were coded for relationship themes like peer acceptance and problem solving, and responses were compared between groups identified based on pas maltreatment. The maltreatment group included 43 children who were identified as having been physically abused, sexually abused, or neglected or having psychologically unavailable care. A control group of 53 children from this high-risk sample was identified as having received adequate care. The remaining participants whose care was questionable were not included in this study. Based on quantitative analyses using a factor measuring relationship expectations and controlling for IQ and socioeconoraic status, the maltreate group told stories significantly more negative compared to the control group. Findings are introduced and discussed in terms of attachment theory and related work addressing the mental representations of maltreated children. In particular, it is proposed that, based on early maltreatment experiences, children acquire internal working models of themselves as unworthy and of others as unavailable. In subsequent relationship situations they would be constricted in cognitively processing events, have difficulty regulating their own emotions, an employ processes of defensive exclusion (e.g. projection, introjection, displacement, splitting, preoccupatioi idealization) to manage their distress feelings.

This study examined whether risk status and cumulative risk were associated with autonomic nervous system reactivity and recovery, and emotion regulation in infants. The sample included 121 6-month-old infants. Classification of risk status was based on World Health Organization criteria (e.g., presence of maternal psychopathology, substance use, and social adversity). Heart rate, parasympathetic respiratory sinus arrhythmia, and sympathetic preejection period were examined at baseline and across the still face paradigm. Infant emotion regulation was coded during the still face paradigm. Infants in the high-risk group showed increased heart rate, parasympathetic withdrawal, and sympathetic activation during recovery from the still face episode. Higher levels of cumulative risk were associated with increased sympathetic nervous system activation. Moreover, increased heart rate during recovery in the high-risk group was mediated by both parasympathetic and sympathetic activity, indicating mobilization of sympathetic resources when confronted with socioemotional challenge. Distinct indirect pathways were observed from maternal risk to infant emotion regulation during the still face paradigm through parasympathetic and sympathetic regulation. These findings underline the importance of specific measures of parasympathetic and sympathetic response and recovery, and indicate that maternal risk is associated with maladaptive regulation of stress early in life reflecting increased risk for later psychopathology.

While environmental adversity has been shown to increase risk for psychopathology, individuals differ in their sensitivity to these effects. Both genes and childhood experiences are thought to influence sensitivity to the environment, and these factors may operate synergistically such that the effects of childhood experiences on later sensitivity are greater in individuals who are more genetically sensitive. In line with this hypothesis, several recent studies have reported a significant three-way interaction (Gene × Environment × Environment) between two candidate genes and childhood and adult environment on adult psychopathology. We aimed to replicate and extend these findings in a large, prospective multiwave longitudinal study using a polygenic score of environmental sensitivity and objectively measured childhood and adult material environmental quality. We found evidence for both Environment × Environment and Gene × Environment × Environment effects on psychological distress. Children with a poor-quality material environment were more sensitive to the negative effects of a poor environment as adults, reporting significantly higher psychological distress scores. These effects were further moderated by a polygenic score of environmental sensitivity. Genetically sensitive children were more vulnerable to adversity as adults, if they had experienced a poor childhood environment but were significantly less vulnerable if their childhood environment was positive. These findings are in line with the differential susceptibility hypothesis and suggest that a life course approach is necessary to elucidate the role of Gene × Environment in the development of mental illnesses.

Accelerated pubertal development has been linked to adverse early environments and may heighten subsequent mental and physical health risks. Hypothalamic–pituitary–adrenal axis functioning has been posited as a mechanism whereby stress may affect pubertal development, but the literature lacks prospective tests of this mechanism. The current study assessed 277 youth (M = 10.84 years, SD = 1.14), 138 boys and 139 girls, who reported on their pubertal development and underwent the Trier Social Stress Test for Children at baseline and returned to the laboratory approximately 1 year later (M = 1.12 years, range = 0.59–1.98 years). For girls, lower cortisol area under the curve (with respect to ground) at Time 1 predicted more advanced pubertal development at Time 2, controlling for Time 1 pubertal development. This association persisted after additional covariates including age, body mass index, race, and maltreatment history were introduced, and was driven by adrenal rather than gonadal development. Cortisol was not linked to boys' subsequent pubertal development, and no interaction by gender or by maltreatment appeared. These results suggest that attenuated cortisol, reported in other studies of children exposed to early adversity, may contribute to accelerated pubertal tempo in girls.

Borderline personality disorder (BPD) is one of the more vexing forms of psychopathology for researchers and clinicians alike to understand. Currently, the etiology and pathogenesis of the disorder remain unclear; however, steady progress has been made in several important areas that bear upon informing a more complete understanding of this condition. Long known to clinicians in office practice and mental health staff at clinics and hospitals, BPD is a heterogenous phenotype characterized by a complex array of features such as emotional dysregulation, interpersonal dysfunction, impulsivity, self-damaging behaviors, excessive anger and fear, and identity disturbance (American Psychiatric Association, 1994). The individual afflicted with BPD frequently experiences substantial social and occupational impairment, as well as frequent emotional turmoil. Those individuals who spend considerable time with a BPD-affected person, such as parents, partners, spouses, children, coworkers, and others, also encounter appreciable stresses and strains associated with the impact of BPD on the family, social, and occupational milieu.

Research suggests that depressive personality (DP) disorder may represent a persistent, trait-based form of depression that lies along an affective spectrum ranging from personality traits to diagnosable clinical disorders. A significant gap in this area of research concerns the development of DP and its applicability to youth. The present research explored the construct of DP traits in youth. Specifically, this study examined the reliability, stability, and validity of the construct, potential origins of DP traits, and the developmental consequences of DP traits. A sample of 143 youth (mean age = 12.37 years, SD = 1.26) and their caregivers completed semistructured interviews and questionnaires on two occasions, separated by a 12-month interval. The measure of DP traits was reliable and moderately stable over time. Providing evidence of construct validity, DP traits were associated with a network of constructs, including a negative self-focus, high-negative and low-positive emotionality, and heightened stress reactivity. Moreover, several potential origins of DP traits were identified, including a history of family adversity, maternal DP traits, and maternal depression. Consistent with hypotheses regarding their developmental significance, DP traits predicted the generation of stress and the emergence of depression (but not nondepressive psychopathology) during the pubertal transition. Finally, depression predicted subsequent DP traits, suggesting a reciprocal process whereby DP traits heighten risk for depression, which then exacerbates these traits. These findings support the construct of DP traits in youth, and suggest that these traits may be a useful addition to developmental models of risk for youth depression.

The hypothalamic–pituitary–adrenal (HPA) axis is sensitive to early life stress, with enduring consequences for biological stress vulnerability and health (Gunnar & Talge, 2008). Low socioeconomic status (SES) is associated with dysregulation of the stress hormone cortisol in early childhood. However, a mechanistic understanding of this association is lacking. Multidimensional assessment of both SES and cortisol is needed to characterize the intricate relations between SES and cortisol function in early childhood. We assessed parent-reported family income, parent education, occupational prestige, neighborhood risk, food insecurity, and household chaos for 12-month-old infants (N = 90) and 3.5-year-old children (N = 91). Hair cortisol concentration (HCC) was obtained from parent and child, indexing chronic biological stress, and diurnal salivary cortisol was measured in the children. Controlling for parent HCC, parent education uniquely predicted infant and child HCC and, in addition, neighborhood risk uniquely predicted infant HCC. Household chaos predicted bedtime salivary cortisol concentration (SCC) for both infants and children, and infant daily cortisol output. Food insecurity was associated with flattened cortisol slope in 3.5-year-old children. Parental sensitivity did not mediate relations between SES and cortisol. Results highlight the utility of SES measures that index unpredictable and unsafe contexts, such as neighborhood risk, food insecurity, and household chaos.

The aim of this study is to examine the association between maternal adverse childhood experiences (ACEs) and mental health problems in adolescent offspring. Data were obtained from the population-based Kochi Child Health Impact of Living Difficulty (K-CHILD) study in 2016, and participants were 10,810 children in the fifth grade (3,144 pairs), eighth grade (3,497 pairs), and eleventh grade (4,169 pairs) living in Kochi Prefecture, Japan. Mothers of participating children were asked about their ACEs, childhood social economic status, current mental and physical health, current social economic status, positive parenting behaviors, child maltreatment, marital status, and child behavior problems using the Strength and Difficulty Questionnaire. Children reported their depressive symptoms using the Depression Self-Rating Scale. Children of mothers with a larger number of ACEs showed higher levels of behavior problems (p for trend <.001) and depressive symptoms (p for trend <.001), adjusting for potential confounders. In particular, maternal psychological distress mediated the association between maternal ACEs and child mental health. The adverse effects of maternal ACEs may have a direct intergenerational impact on behavior problems and depressive symptoms in adolescent offspring. Further studies to elucidate possible mediators are needed.

Developmental language learning impairments (LLI) are one of the most prevalent of all developmental disabilities, can occur in children for a wide variety of reasons, and have been shown to co-occur frequently with other developmental social, emotional and behavioral disorders, as well as with academic achievement problems. Research pertaining to developmental LLI of unknown origin, with an emphasis on the continuum between oral and written language impairment, is the focus of this review. Given the complexity of language learning, research has focused on multiple levels of analysis, including linguistic, neuropsychological, genetic, neurobiological, and remediation studies. To date, the vast majority of data on LLI derive from studies focused on a single level of analysis. Although attempts have been made to integrate data across studies and multiple levels of analysis, this has proven to be problematic, given the heterogeneity of the subject populations used to study LLI, as well as the differences in ages, degree of impairment, and types of impairment included in each study. Given that LLI is a complex developmental disability, it is suggested that future research would benefit from taking a multiple levels of analysis approach with the same individuals, incorporating mathematical models designed to analyze dynamically changing complex systems, and studying individual differences in language learning, prospectively and longitudinally, throughout the most dynamic stages of the process.

A new theory of frontal lobe development is presented in which the role of the human frontal lobes during normal development and the psychopathological consequences of early frontal lobe injury are explored. Analyses of the development of human electroencephalograph (EEG) coherence indicate that there are oscillations and cyclic growth processes along the mediolateral and anterior-posterior planes of the brain. The cycles of EEG coherence are interpreted as repetitive sequences of increasing and decreasing synaptic effectiveness that reflects a convergence process that narrows the disparity between structure and function by slowly sculpting and reshaping the brain's microanatomy. This process is modeled as a developmental spiral staircase in which brain structures are periodically revisited resulting in stepwise increases in differentiation and integration. The frontal lobes play a crucial role because they are largely responsible for the selection and pruning of synaptic contacts throughout the postnatal period. A mathematical model of cycles of synaptic effectiveness is presented in which the frontal lobes behave as gentle synaptic “predators” whereas posterior cortical regions behave as synaptic “prey” in a periodic reorganization process. The psychopathological consequences of early frontal lobe damage are discussed in the context of this model.

This study examined genetic and environmental influences on associations among marital conflict about the child, parental monitoring, sibling relationship negativity, and peer delinquency during adolescence and initiation of illegal drug use by young adulthood. The sample comprised data collected longitudinally from same-sex sibling pairs and parents when the siblings were 10–18 years old (M = 14.5 and 12.9 years for Child 1 and Child 2, respectively) and 20–35 years old (M = 26.8 and 25.5 years for Child 1 and Child 2, respectively). Findings indicate four factors that explain the initiation of illegal drug use: two shaped by genetic influences and two shaped by environments shared by siblings. The two genetically shaped factors probably have distinct mechanisms: one a child-initiated coercive process in the family and the other parent and peer processes shaped by the child's disclosure. The environmentally influenced factors seem distinctively shaped by poor parental monitoring of both sibs and the effects of siblings on each other's deviancy.

Data drawn from the in-home subsample of the PROSPER intervention dissemination trial were used to investigate the moderation of intervention effects on underage alcohol use by maternal involvement and candidate genes. The primary gene examined was dopamine receptor D4 (DRD4). Variation in this gene and maternal involvement were hypothesized to moderate the influence of intervention status on alcohol use. The PROSPER data used were drawn from 28 communities randomly assigned to intervention or comparison conditions. Participating youth were assessed in five in-home interviews from sixth to ninth grades. A main effect of sixth-grade pretest maternal involvement on ninth-grade alcohol use was found. Neither intervention status nor DRD4 variation was unconditionally linked to ninth-grade drinking. However, moderation analyses revealed a significant three-way interaction among DRD4 status, maternal involvement, and intervention condition. Follow-up analyses revealed that prevention reduced drinking risk, but only for youth with at least one DRD4 seven-repeat allele who reported average or greater pretest levels of maternal involvement. To determine if this conditional pattern was limited to the DRD4 gene, we repeated analyses using the serotonin transporter linked polymorphic region site near the serotonin transporter gene. The results for this supplemental analysis revealed a significant three-way interaction similar but not identical to that found for DRD4.

The co-occurrence of conduct problems (CP) and depressive symptoms (DS) is an important topic in developmental psychopathology; however, research in this area is still in its early stages. Using data from a school-based longitudinal sample of 2,453 adolescents with five waves from Grade 6 to 9, we examined the prevalence, etiology, and consequences of the co-occurrence of CP and DS. A person-centered approach, general growth mixture modeling, was applied to obtain CP and DS trajectory groups. The risk factors and consequences of the co-occurrence problem were examined using the trajectory groups. As hypothesized in a nonclinical sample, a small proportion of boys (8.8%) and girls (3.7%) reported to be high in both CP and DS over time. Among the adolescents with the highest level of CP, only 6.3% of the boys and 6.0% of the girls experienced the highest level of DS. However, among those with the highest level of DS trajectories, 42.9% of the boys and 10.2% of the girls reported the highest level of CP, indicating a gender-specific risk of the co-occurrence problem for depressed boys. Psychosocial and family factors were identified as vulnerable precursors to co-occurring CP and DS, a finding in line with the multiple domain risk model for CP and the transactional model for DS. The study also found that adolescents with the co-occurrence problem were more similar to those with “pure DS” than those with “pure CP” in academic adjustment at the ninth grade.

The present study examined the impact of children's maltreatment experiences on the emergence of externalizing problem presentations among children during different developmental periods. The sample included 788 youth and their caregivers who participated in a multisite, prospective study of youth at-risk for maltreatment. Externalizing problems were assessed at ages 4, 8, and 12, and symptoms and diagnoses of attention-deficit/hyperactivity disorder, oppositional defiant disorder, and conduct disorder were assessed at age 14, during interviews with youth and caregivers. Information about maltreatment allegations was coded from official records. Latent transition analysis identified three groups of youth with similar presentations of externalizing problems (“well adjusted,” “hyperactive/oppositional,” and “aggressive/rule-breaking”) and transitions between groups from ages 4, 8, and 12. A “defiant/deceitful” group also emerged at age 12. Girls were generally more likely to present as well adjusted than boys. Children with recent physical abuse allegations had an increased risk for aggressive/rule-breaking presentations during the preschool and preadolescent years, while children with sexual abuse or neglect allegations had lower probabilities of having well-adjusted presentations during middle childhood. These findings indicate that persistently severe aggressive conduct problems, which are related to the most concerning outcomes, can be identified early, particularly among neglected and physically and sexually abused children.