Structure of Psychopathology in Romanian Preschool-Aged Children in an Epidemiological and a High-Risk Sample.

Objective: Research on bifactor models of psychopathology in early childhood is limited to community samples with little longitudinal follow-up. We examined general and specific forms of psychopathology within 2 independent samples of preschool-aged Romanian children. Within a sample with children exposed to psychosocial deprivation, we also examined antecedents and longitudinal outcomes of the general factor. Method: One sample consisted of 350 Romanian children (mean age = 39.7 months, SD = 10.9) from an epidemiological study; the second sample consisted of 170 Romanian children (mean age = 55.6 months, SD = 1.9) exposed to severe early-life deprivation, as well as community comparison children, with longitudinal follow-up at 8 and 12 years. Psychopathology symptoms were assessed through caregiver-reported structured clinical interviews. Results: An SI-1 bifactor model of psychopathology was supported in both samples and included specific factors for externalizing, internalizing, and disturbed relatedness symptoms. In the second sample, longer duration of psychosocial deprivation and lower-quality caregiving were associated with higher scores on the general and all specific factors. Higher scores on the general factor were associated with later cognitive function, competence, and psychopathology symptoms. Considering all factors together, only the general factor explained variance in later childhood outcomes and was slightly stronger compared to a total symptom count for some, but not all, outcomes. Conclusion: General psychopathology in early childhood explains meaningful variance in child outcomes across multiple domains of functioning in later childhood. However, important questions remain regarding its clinical utility and usefulness, given complex measurement and limited explanatory power beyond the more accessible approach of a total symptom count. Clinical trial registration information: The Bucharest Early Intervention Project; https://clinicaltrials.gov/; NCT00747396.

Early caregiving quality predicts consistency of competent functioning from middle childhood to adolescence following early psychosocial deprivation.

Adverse developmental outcomes for some children following institutional care are well established. Removal from institutional care and placement into families can promote recovery. However, little is known about how positive outcomes are sustained across adolescence among children with histories of severe deprivation. The present study examined the caregiving conditions that are associated with attaining and maintaining competent functioning (i.e., outcomes within typical levels) from middle childhood to adolescence following exposure to early institutional care. The participants included children with and without a history of institutional care who had competence assessed at ages 8, 12, and 16 years across seven domains: family relationships, peer relationships, academic performance, physical health, mental health, substance use (ages 12 and 16 years only), and risk-taking behavior. The participants were grouped based on whether they were always versus not always competent and never versus ever competent at ages 8 through 16 years. Adolescents with a history of institutional care were less likely to be consistently competent than those who were family reared. Among those who were exposed to early institutional rearing, maintaining competent functioning from 8 to 16 years was associated with spending less time in institutions and receiving higher-quality caregiving early in life. Ensuring high quality early caregiving may promote competent functioning following early deprivation.

Heightened sensitivity to the caregiving environment during adolescence: implications for recovery following early-life adversity.

BACKGROUND: Adolescence has been proposed to be a period of heightened sensitivity to environmental influence. If true, adolescence may present a window of opportunity for recovery for children exposed to early-life adversity. Recent evidence supports adolescent recalibration of stress response systems following early-life adversity. However, it is unknown whether similar recovery occurs in other domains of functioning in adolescence. METHODS: We use data from the Bucharest Early Intervention Project - a randomized controlled trial of foster care for children raised in psychosocially depriving institutions - to examine the associations of the caregiving environment with reward processing, executive functioning, and internalizing and externalizing psychopathology at ages 8, 12, and 16 years, and evaluate whether these associations change across development. RESULTS: Higher quality caregiving in adolescence was associated with greater reward responsivity and lower levels of internalizing and externalizing symptoms, after covarying for the early-life caregiving environment. The associations of caregiving with executive function and internalizing and externalizing symptoms varied by age and were strongest at age 16 relative to ages 8 and 12 years. This heightened sensitivity to caregiving in adolescence was observed in both children with and without exposure to early psychosocial neglect. CONCLUSIONS: Adolescence may be a period of heightened sensitivity to the caregiving environment, at least for some domains of functioning. For children who experience early psychosocial deprivation, this developmental period may be a window of opportunity for recovery of some functions. Albeit correlational, these findings suggest that it may be possible to reverse or remediate some of the lasting effects of early-life adversity with interventions that target caregiving during adolescence.

Psychiatric outcomes following severe deprivation in early childhood: Follow-up of a randomized controlled trial at age 16.

OBJECTIVE: Early psychosocial deprivation is associated with increased risk for psychopathology, yet few studies have examined outcomes in adolescents. METHOD: At baseline (M age 22 months), 136 children from Bucharest, Romania, living in large institutions, were randomized into foster care (FCG) or to care as usual (CAUG). Caregivers completed psychiatric interviews regarding their children (52 FCG; 51 CAUG) at age 16 years (M = 16.67 years; SD = 0.78) to assess past year diagnoses and symptom counts. In addition, never-institutionalized community comparison children (n = 47) were included. RESULTS: Ever-institutionalized children had higher rates of meeting criteria for any psychiatric disorder and higher symptom counts of internalizing, externalizing, attention-deficit/hyperactivity, and substance use disorders compared to never-institutionalized children (ps < .05). Using intent-to-treat analyses, we found that children in the CAUG had more than twice the rate of psychiatric disorders than children in the FCG (OR = 2.48, 95% CI [1.12, 5.48]). Furthermore, children in foster care who remained in their original placement did not significantly differ in their rates of psychiatric disorders compared to never-institutionalized children. CONCLUSIONS: There are many ways children can be separated from parents, including placement into institutional care. The current findings indicate that such placements are associated with significant risks for psychopathology. Moreover, we provide causal evidence for the long-lasting positive effect of foster care in reducing the risk of psychopathology in adolescence, especially among those in stable placements. These results provide strong evidence that early and stable placements into quality foster care may mitigate risk for psychopathology following severe early psychosocial deprivation. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Stress sensitization among severely neglected children and protection by social enrichment.

Childhood adversity may sensitize certain individuals to later stress which triggers or amplifies psychopathology. The current study uses data from a longitudinal randomized controlled trial to examine whether severe early neglect among children reared in institutions increases vulnerability to the effects of later stressful life events on externalizing problems in adolescence, and whether social enrichment in the form of high-quality foster care buffers this risk. Children abandoned to Romanian institutions were randomly assigned to a foster care intervention or care-as-usual during early childhood. A sample of never-institutionalized children served as a comparison group. Here we report that, among those with prolonged institutional rearing, more stressful life events in preadolescence predicted higher externalizing problems in adolescence. This effect was not observed for never-institutionalized children or those in foster care, thus providing experimental evidence that positive caregiving experiences protect against the stress-sensitizing effects of childhood neglect on externalizing problems in adolescence.

Sex differences in the associations between vagal reactivity and oppositional defiant disorder symptoms.

BACKGROUND: Vagal reactivity to stress in children has been associated with future psychiatric outcomes. However, results have been mixed possibly because these effects are in opposite direction in boys and girls. These sex differences are relevant in the context of development of psychopathology, whereby the rates of psychiatric disorders differ by sex. In this study, we aimed to examine the association between vagal reactivity, assessed as a reduction in respiratory sinus arrhythmia (RSA) in response to a challenge, and the development of future oppositional defiant disorder (ODD) symptoms in boys and girls. In addition, we examine the specific associations with ODD symptom dimensions, named irritability and headstrong. We hypothesized that increased vagal reactivity was associated with increased ODD symptoms in girls and a reduction in ODD symptoms in boys. METHODS: Participants were members of the Wirral Child Health and Development Study, a prospective epidemiological longitudinal study of 1,233 first-time mothers recruited at 20 weeks' gestation. RSA during four nonstressful and one stressful (still-face) procedures was assessed when children were aged 29 weeks in a sample stratified by adversity (n = 270). Maternal reports of ODD symptoms were collected when children were 2.5 years old (n = 253), 3.5 years old (n = 826), and 5 years old (n = 770). Structural equation modeling (SEM) was employed to test our hypotheses. RESULTS: There was a significant sex difference in the prediction of ODD symptoms due to the opposite directionality in which increasing vagal reactivity was associated with an increase in ODD symptoms in girls and a reduction of ODD symptoms in boys. This Sex by Vagal reactivity interaction was common for both ODD dimensions, with no sex by dimension-specific associations. CONCLUSIONS: Physiological reactivity to a stressful situation predicts differently ODD symptoms in boys and girls very early in life, with no difference across irritability and headstrong components. Findings are discussed in the context of the several mechanisms involved on the later development of distinct psychiatric disorders in boys and girls.

Maternal prenatal cortisol predicts infant negative emotionality in a sex-dependent manner.

OBJECTIVE: Prenatal stress influences fetal developmental trajectories, which may implicate glucocorticoid mechanisms. There is also emerging evidence that effects of prenatal stress on offspring development are sex-dependent. However, little is known about the prospective relationship between maternal prenatal cortisol levels and infant behaviour, and whether it may be different in male and female infants. We sought to address this question using data from a prospective longitudinal cohort, stratified by risk. METHOD: The Wirral Child Health and Development Study (WCHADS) cohort (n=1233) included a stratified random sub-sample (n=216) who provided maternal saliva samples, assayed for cortisol, at home over two days at 32weeks of pregnancy (on waking, 30-min post-waking and during the evening) and a measure of infant negative emotionality from the Neonatal Behavioural Assessment Scale (NBAS) at five weeks-of-age. General population estimates of associations among measures were obtained using inverse probability weights. RESULTS: Maternal prenatal cortisol sampled on waking predicted infant negative emotionality in a sex-dependent manner (interaction term, p=0.005); female infants exposed to high levels of prenatal cortisol were more negative (Beta=0.440, p=0.042), whereas male infants were less negative (Beta=-0.407, p=0.045). There was no effect of the 30-min post-waking measure or evening cortisol. DISCUSSION: Our findings add to an emerging body of work that has highlighted sex differences in fetal programming, whereby females become more reactive following prenatal stress, and males less reactive. A more complete understanding of sex-specific developmental trajectories in the context of prenatal stress is essential for the development of targeted prevention strategies.

Reduced Working Memory Mediates the Link between Early Institutional Rearing and Symptoms of ADHD at 12 Years.

Children who are raised in institutions show severe delays across multiple domains of development and high levels of psychopathology, including attention deficit/hyperactivity disorder (ADHD). Low performance in executive functions (EFs) are also common in institutionally reared children and often do not remediate following improvements in the caregiving environment. ADHD symptomatology also remains elevated even after children are removed from institutional care and placed in families. We investigate whether poor EF is a mechanism explaining elevated rates of ADHD in children reared in institutional settings in the Bucharest Early Intervention Project (BEIP). In the current study, we examine the potentially mediating role of poor EF in the association between institutionalization and symptoms of ADHD at age 12 years. A total of 107 children were assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB) on working memory, set-shifting and planning. We also obtained concurrent teacher reports on their levels of ADHD symptoms (inattention and impulsivity separately). Institutionalization strongly predicted elevations in symptoms of inattention and impulsivity at age 12 years (ps < 0.01). Indices of working memory and planning were also associated with ADHD after controlling for potential confounders (ps < 0.03). Mediation analyses revealed that poor working memory performance mediated the link between exposure to early institutionalization and higher scores of both inattention and impulsivity. These results replicate and extend the findings that we reported in the BEIP sample at age 8 years. Together, they suggest that compromised working memory is a key mechanism that continues to explain the strikingly high levels of ADHD in late childhood among children institutionalized in early life. Interventions targeting working memory may help to prevent ADHD among children exposed to institutional care.

Causal effects of the early caregiving environment on development of stress response systems in children.

Disruptions in stress response system functioning are thought to be a central mechanism by which exposure to adverse early-life environments influences human development. Although early-life adversity results in hyperreactivity of the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis in rodents, evidence from human studies is inconsistent. We present results from the Bucharest Early Intervention Project examining whether randomized placement into a family caregiving environment alters development of the autonomic nervous system and HPA axis in children exposed to early-life deprivation associated with institutional rearing. Electrocardiogram, impedance cardiograph, and neuroendocrine data were collected during laboratory-based challenge tasks from children (mean age = 12.9 y) raised in deprived institutional settings in Romania randomized to a high-quality foster care intervention (n = 48) or to remain in care as usual (n = 43) and a sample of typically developing Romanian children (n = 47). Children who remained in institutional care exhibited significantly blunted SNS and HPA axis responses to psychosocial stress compared with children randomized to foster care, whose stress responses approximated those of typically developing children. Intervention effects were evident for cortisol and parasympathetic nervous system reactivity only among children placed in foster care before age 24 and 18 months, respectively, providing experimental evidence of a sensitive period in humans during which the environment is particularly likely to alter stress response system development. We provide evidence for a causal link between the early caregiving environment and stress response system reactivity in humans with effects that differ markedly from those observed in rodent models.

Evidence for sex differences in fetal programming of physiological stress reactivity in infancy.

Associations between low birth weight and prenatal anxiety and later psychopathology may arise from programming effects likely to be adaptive under some, but not other, environmental exposures and modified by sex differences. If physiological reactivity, which also confers vulnerability or resilience in an environment-dependent manner, is associated with birth weight and prenatal anxiety, it will be a candidate to mediate the links with psychopathology. From a general population sample of 1,233 first-time mothers recruited at 20 weeks gestation, a sample of 316 stratified by adversity was assessed at 32 weeks and when their infants were aged 29 weeks (N = 271). Prenatal anxiety was assessed by self-report, birth weight from medical records, and vagal reactivity from respiratory sinus arrhythmia during four nonstressful and one stressful (still-face) procedure. Lower birth weight for gestational age predicted higher vagal reactivity only in girls (interaction term, p = .016), and prenatal maternal anxiety predicted lower vagal reactivity only in boys (interaction term, p = .014). These findings are consistent with sex differences in fetal programming, whereby prenatal risks are associated with increased stress reactivity in females but decreased reactivity in males, with distinctive advantages and penalties for each sex.

Psychopathology in young children in two types of foster care following institutional rearing.

Institutional rearing of young children has been demonstrated to increase risk for a broad range of psychiatric disorders and other impairments. This has led many countries to consider or to invest in foster care. However, no study to date has explored potential differences in psychiatric symptoms in children placed in different types of foster care. We assessed internalizing disorders, externalizing disorders, and attention deficit hyperactivity disorder (ADHD) in 54-month-old children living with foster families. We compared one group of children living in high-quality foster families who had benefited from specialized training and support to another group of children placed with government-sponsored foster care in Bucharest, Romania. After controlling for duration of time spent in foster care, there was a main group effect in predicting ADHD (p = .021) and a marginal group × gender interaction effect. No effects were noted for signs of externalizing disorders. There was, however, a significant group × gender interaction effect of signs of internalizing disorders (p = .007), with the girls in high-quality foster care having less severe symptomatology than did their counterparts in the government-sponsored group. Governments must invest in quality interventions for their most vulnerable citizens to prevent serious and potentially lasting problems.

Frequency of infant stroking reported by mothers moderates the effect of prenatal depression on infant behavioural and physiological outcomes.

Animal studies find that prenatal stress is associated with increased physiological and emotional reactivity later in life, mediated via fetal programming of the HPA axis through decreased glucocorticoid receptor (GR) gene expression. Post-natal behaviours, notably licking and grooming in rats, cause decreased behavioural indices of fear and reduced HPA axis reactivity mediated via increased GR gene expression. Post-natal maternal behaviours may therefore be expected to modify prenatal effects, but this has not previously been examined in humans. We examined whether, according to self-report, maternal stroking over the first weeks of life modified associations between prenatal depression and physiological and behavioral outcomes in infancy, hence mimicking effects of rodent licking and grooming. From a general population sample of 1233 first time mothers recruited at 20 weeks gestation we drew a stratified random sample of 316 for assessment at 32 weeks based on reported inter-partner psychological abuse, a risk to child development. Of these 271 provided data at 5, 9 and 29 weeks post delivery. Mothers reported how often they stroked their babies at 5 and 9 weeks. At 29 weeks vagal withdrawal to a stressor, a measure of physiological adaptability, and maternal reported negative emotionality were assessed. There was a significant interaction between prenatal depression and maternal stroking in the prediction of vagal reactivity to a stressor (p = .01), and maternal reports of infant anger proneness (p = .007) and fear (p = .043). Increasing maternal depression was associated with decreasing physiological adaptability, and with increasing negative emotionality, only in the presence of low maternal stroking. These initial findings in humans indicate that maternal stroking in infancy, as reported by mothers, has effects strongly resembling the effects of observed maternal behaviours in animals, pointing to future studies of the epigenetic, physiological and behavioral effects of maternal stroking.