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The interactions most supportive of positive child development take place in moments of close contact with others. In the earliest years of life, a child's caregivers are the primary partners in these important interactions. Little is known about the patterns of real-life physical interactions between children and their caregivers, in part due to an inability to measure these interactions as they occur in real time. We have developed a wearable, infrastructure-free device (TotTag) used to dynamically and unobtrusively measure physical proximity between children and caregivers in real time. We present a case-study illustration of the TotTag with data collected over two (12-hour) days each from two families: a family of four (30-month-old son, 61-month-old daughter, 37-year-old father, 37-year-old mother), and a family of three (12-month-old daughter, 35-year-old-father, 33-year-old mother). We explored patterns of proximity within each parent-child dyad and whether close proximity would indicate periods in which increased opportunity for developmentally critical interactions occur. Each child also wore a widely used wearable audio recording device (LENA) to collect time-synced linguistic input. Descriptive analyses reveal wide variability in caregiver-child proximity both within and across dyads, and that the amount of time spent in close proximity with a caregiver is associated with the number of adult words and conversational turns to which a child was exposed. This suggests that variations in proximity are linked to-though, critically, not synonymous with-the quantity of a child's exposure to adult language. Potential implications for deepening the understanding of early caregiver-child interactions are discussed., (© 2021. The Psychonomic Society, Inc.)

The early environment, including maternal characteristics, provides many cues to young organisms that shape their long-term physical and mental health. Identifying the earliest molecular events that precede observable developmental outcomes could help identify children in need of support prior to the onset of physical and mental health difficulties. In this study, we examined whether mothers' attachment insecurity, maltreatment history, and depressive symptoms were associated with alterations in DNA methylation patterns in their infants, and whether these correlates in the infant epigenome were associated with socioemotional and behavioral functioning in toddlerhood. We recruited 156 women oversampled for histories of depression, who completed psychiatric interviews and depression screening during pregnancy, then provided follow-up behavioral data on their children at 18 months. Buccal cell DNA was obtained from 32 of their infants for a large-scale analysis of methylation patterns across 5 × 10 6 individual CpG dinucleotides, using clustering-based significance criteria to control for multiple comparisons. We found that tens of thousands of individual infant CpGs were alternatively methylated in association with maternal attachment insecurity, maltreatment in childhood, and antenatal and postpartum depressive symptoms, including genes implicated in developmental patterning, cell-cell communication, hormonal regulation, immune function/inflammatory response, and neurotransmission. Density of DNA methylation at selected genes from the result set was also significantly associated with toddler socioemotional and behavioral problems. This is the first report to identify novel regions of the human infant genome at which DNA methylation patterns are associated longitudinally both with maternal characteristics and with offspring socioemotional and behavioral problems in toddlerhood., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The amygdala and its connections with medial prefrontal cortex (mPFC) play central roles in the development of emotional processes. While several studies have suggested that this circuitry exhibits functional changes across the first two decades of life, findings have been mixed - perhaps resulting from differences in analytic choices across studies. Here we used multiverse analyses to examine the robustness of task-based amygdala-mPFC function findings to analytic choices within the context of an accelerated longitudinal design (4-22 years-old; N = 98; 183 scans; 1-3 scans/participant). Participants recruited from the greater Los Angeles area completed an event-related emotional face (fear, neutral) task. Parallel analyses varying in preprocessing and modeling choices found that age-related change estimates for amygdala reactivity were more robust than task-evoked amygdala-mPFC functional connectivity to varied analytical choices. Specification curves indicated evidence for age-related decreases in amygdala reactivity to faces, though within-participant changes in amygdala reactivity could not be differentiated from between-participant differences. In contrast, amygdala-mPFC functional connectivity results varied across methods much more, and evidence for age-related change in amygdala-mPFC connectivity was not consistent. Generalized psychophysiological interaction (gPPI) measurements of connectivity were especially sensitive to whether a deconvolution step was applied. Our findings demonstrate the importance of assessing the robustness of findings to analysis choices, although the age-related changes in our current work cannot be overinterpreted given low test-retest reliability. Together, these findings highlight both the challenges in estimating developmental change in longitudinal cohorts and the value of multiverse approaches in developmental neuroimaging for assessing robustness of results., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Peripartum depressive symptoms are associated with a range of adverse outcomes for offspring and mothers. Childhood experiences, both negative and positive, may impact peripartum depression risk. Longitudinal studies are needed to examine trajectories of change in depression across the peripartum and predictors of symptoms across time. We examined the associations between women's reports of specific childhood experiences and trajectories of depressive symptoms across the peripartum period. Participants were 208 pregnant women ( M age=30.31, SD =5.45, range=20-45 years) at the prenatal session. Participants completed follow up sessions approximately 1 month and 6 months postpartum. At baseline, participants completed questionnaire measures of benevolent childhood experiences, childhood maltreatment, and depressive symptoms. Greater benevolent childhood experiences were associated with lower depressive symptoms across the peripartum period. The association with postpartum symptoms remained significant even when covarying antepartum depressive symptoms, indicating that benevolent childhood experiences may protect against postpartum depressive symptoms even after accounting for earlier symptoms. We did not find significant associations between childhood maltreatment and depressive symptoms. These findings extend previous research on benevolent childhood experiences by offering insight into unique associations with symptoms across the peripartum period., Competing Interests: Conflict of interest/Competing interests: Not applicable.

Human infancy and early childhood is both a time of heightened brain plasticity and responsivity to the environment as well as a developmental period of dependency on caregivers for survival, nurturance, and stimulation. Across primate species and human evolutionary history, close contact between infants and caregivers is species-expected. As children develop, caregiver-child proximity patterns change as children become more autonomous. In addition to developmental changes, there is variation in caregiver-child proximity across cultures and families, with potential implications for child functioning. We propose that caregiver-child proximity is an important dimension for understanding early environments, given that interactions between children and their caregivers are a primary source of experience-dependent learning. We review approaches for operationalizing this construct (e.g., touch, physical distance) and highlight studies that illustrate how caregiver-child proximity can be measured. Drawing on the concepts proposed in dimensional models of adversity, we consider how caregiver-child proximity may contribute to our understanding of children's early experiences. Finally, we discuss future directions in caregiver-child proximity research with the goal of understanding the link between early experiences and child adaptive and maladaptive functioning.

Background: Experiences of adversity in early life are associated with increased risk for negative outcomes; yet, the impact of early adversity on any given child is difficult to predict given the considerable heterogeneity in functioning found even among children with similar exposures. Thus, although early adversity is associated with increased risk for negative outcomes on average, many children are resilient. While researchers have highlighted individual differences in children's internal characteristics that may relate to risk and resilience, external characteristics of the environment that differ between children are mutable factors that are also important for understanding heterogeneity in children's outcomes., Objective: We propose that caregiver regulation of children's emotions is a key modifiable feature of the environment that promotes resilience to and recovery from early adversity. Specifically, given the critical role of caregiver regulation of emotions in early life for children's ability to understand and recover from adverse experiences, we highlight three levels of intervention focused on fostering healthy development in young children by targeting the availability, consistency, and quality of caregiver regulation, respectively., Results: We provide a classification system designed to guide decision making about the level of intervention needed to support a given child's needs in terms of ultimately supporting the goal of receiving effective caregiver regulation., Implications: This framework may be useful for guiding the priority of treatments, as well as making clear the needed menu of options to support children following adversity, in addressing specific concerns related to ensuring effective caregiver regulation to promote resilience. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The impact of COVID-19-related stress on perinatal women is of heightened public health concern given the established intergenerational impact of maternal stress-exposure on infants and fetuses. There is urgent need to characterize the coping styles associated with adverse psychosocial outcomes in perinatal women during the COVID-19 pandemic to help mitigate the potential for lasting sequelae on both mothers and infants. This study uses a data-driven approach to identify the patterns of behavioral coping strategies that associate with maternal psychosocial distress during the COVID-19 pandemic in a large multicenter sample of pregnant women (N = 2876) and postpartum women (N = 1536). Data was collected from 9 states across the United States from March to October 2020. Women reported behaviors they were engaging in to manage pandemic-related stress, symptoms of depression, anxiety and global psychological distress, as well as changes in energy levels, sleep quality and stress levels. Using latent profile analysis, we identified four behavioral phenotypes of coping strategies. Critically, phenotypes with high levels of passive coping strategies (increased screen time, social media, and intake of comfort foods) were associated with elevated symptoms of depression, anxiety, and global psychological distress, as well as worsening stress and energy levels, relative to other coping phenotypes. In contrast, phenotypes with high levels of active coping strategies (social support, and self-care) were associated with greater resiliency relative to other phenotypes. The identification of these widespread coping phenotypes reveals novel behavioral patterns associated with risk and resiliency to pandemic-related stress in perinatal women. These findings may contribute to early identification of women at risk for poor long-term outcomes and indicate malleable targets for interventions aimed at mitigating lasting sequelae on women and children during the COVID-19 pandemic., (© 2022. The Author(s).)

Women experience dramatic physiological changes during pregnancy, including changes in the production of the "stress hormone," cortisol. Evidence has been mixed regarding whether hair cortisol concentration (HCC) can be used to accurately capture the trajectory of cortisol during this period and whether factors related to psychosocial stress are related to HCC in pregnant and postpartum women. In the current study, we collected hair samples from 85 individuals during the peripartum period (with collection occasions in pregnancy [12-37 weeks], at 3-8 weeks postpartum, and at 5-8 months postpartum) from which we derived 783 monthly observations of HCC. In addition, at each assessment individuals reported their current depressive symptoms and experiences of recent psychosocial adversity. Using piecewise mixed effects modeling, we identified significant increases in HCC across pregnancy (approximately a 2-fold rise) followed by significant decreases in HCC postpartum. Beyond these effects, however, there was substantial within-individual variability in HCC. Disaggregating between- from within-individual associations of depressive symptoms and adversity with HCC, we found that within-individual fluctuations in adversity were positively coupled with levels of HCC. Overall, the current findings suggest that measurement of cortisol in human hair captures its trajectory from conception through six months postpartum, including prenatal increases and gradual recovery of typical levels following childbirth. In addition to the overall severity of psychosocial adversity, change in women's experiences of adversity during the peripartum period merit attention., Competing Interests: The authors report no conflicts of interest., (© 2021 The Authors.)

The relationships infants and young children have with their caregivers are fundamental to their survival and well-being. Theorists and researchers across disciplines have attempted to describe and assess the variation in these relationships, leading to a general acceptance that caregiving is critical to understanding child functioning, including developmental psychopathology. At the same time, we lack consensus on how to assess these fundamental relationships. In the present paper, we first review research documenting the importance of the caregiver-child relationship in understanding environmental risk for psychopathology. Second, we propose that the National Institute of Mental Health's Research Domain Criteria (RDoC) initiative provides a useful framework for extending the study of children's risk for psychopathology by assessing their caregivers' social processes . Third, we describe the units of analysis for caregiver social processes, documenting how the specific subconstructs in the domain of social processes are relevant to the goal of enhancing knowledge of developmental psychopathology. Lastly, we highlight how past research can inform new directions in the study of caregiving and the parent-child relationship through this innovative extension of the RDoC initiative.

We review the three prevailing approaches-specificity, cumulative risk, and dimensional models-to conceptualizing the developmental consequences of early-life adversity and address fundamental problems with the characterization of these frameworks in a recent Perspectives on Psychological Science piece by Smith and Pollak. We respond to concerns raised by Smith and Pollak about dimensional models of early experience and highlight the value of these models for studying the developmental consequences of early-life adversity. Basic dimensions of adversity proposed in existing models include threat/harshness, deprivation, and unpredictability. These models identify core dimensions of early experience that cut across the categorical exposures that have been the focus of specificity and cumulative risk approaches (e.g., abuse, institutional rearing, chronic poverty); delineate aspects of early experience that are likely to influence brain and behavioral development; afford hypotheses about adaptive and maladaptive responses to different dimensions of adversity; and articulate specific mechanisms through which these dimensions exert their influences, conceptualizing experience-driven plasticity within an evolutionary-developmental framework. In doing so, dimensional models advance specific falsifiable hypotheses, grounded in neurodevelopmental and evolutionary principles, that are supported by accumulating evidence and provide fertile ground for empirical studies on early-life adversity.

Attachment security may be a mechanism by which exposure to early life adversity affects subsequent generations. We used a prospective cohort design to examine this possibility in a convenience sample of 124 women (age = 23-45 years, M = 32.32 [SD = 4.83] years; 57.3% White, 22.6% Asian) who provided self-reports of attachment style during pregnancy using the Attachment Style Questionnaire, of whom 96 (age = 28-50 years, M = 36.67 [SD = 4.90] years; 60.4% White, 19.8% Asian) were reassessed when their child was preschool-age (M = 4.38 [SD = 1.29] years). Women self-reported on their own childhood maltreatment severity and their child's current emotional and behavioral problems using the Childhood Trauma Questionnaire and the Child Behavior Checklist for ages 1.5-5, respectively. Maternal childhood maltreatment severity was associated with less secure, and more avoidant and anxious attachment. Mediation analyses revealed further that less secure maternal attachment, but not avoidant or anxious attachment, mediated the associations between maternal childhood maltreatment and offspring emotional and behavioral problems. These findings suggest that improving maternal attachment security, which can be identified even prior to the child's birth, is an important target to consider for intervention efforts aimed at minimizing adverse intergenerational effects of early life adversity., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

The ability to learn from experience is critical for determining when to take risks and when to play it safe. However, we know little about how within-person state changes, such as an individual's degree of neurophysiological arousal, may impact the ability to learn which risks are most likely to fail vs succeed. To test this, we used a randomized, double-blind, placebo-controlled design to pharmacologically manipulate neurophysiological arousal and assess its causal impact on risk-related learning and performance. Eighty-seven adults (45% female, Mage = 20.1 ± 1.46 years) took either propranolol (n = 42), a beta-adrenergic receptor blocker that attenuates sympathetic nervous system-related signaling, or a placebo (n = 45). Participants then completed the Balloon Emotional Learning Task, a risk-taking task wherein experiential learning is necessary for task success. We found that individuals on propranolol, relative to placebo, earned fewer points on the task, suggesting that they were less effective risk-takers. This effect was mediated by the fact that those on propranolol made less optimal decisions in the final phase of the task on trials with the greatest opportunity for advantageous risk-taking. These findings highlight that neurophysiological arousal supports risk-related learning and, in turn, more advantageous decision-making and optimal behavior under conditions of risk., (© The Author(s) 2021. Published by Oxford University Press.)

The quality of the early environment influences the development of psychopathology. Children who are deprived of sufficient environmental enrichment in infancy may be at higher risk for developing symptoms of psychopathology in toddlerhood. In this study, we investigated the prospective association between naturalistic measures of adult language input obtained through passive monitoring of infants' daily environments and emerging psychopathology in toddlerhood. In a sample of 100 mothers and their infants recruited from the community (mean age [range] = 6.73 [5-9] months), we used the Language ENvironment Analysis (LENA) system to measure multiple dimensions of infants' language environments, including both the quantity and consistency of adult speech and conversational turns in infants' daily lives as well as the quantity of infant vocalizations. Subsequently, during toddlerhood (mean age [range] = 18.29 [17-21] months), mothers reported on their children's symptoms of psychopathology. Infants who experienced more consistent adult speech and conversational turns had lower symptoms of psychopathology in toddlerhood, independent of negative emotionality in infancy, maternal depressive symptoms, and laboratory-based measures of maternal sensitivity. These findings have implications for the measurement of environmental factors that may confer risk and resilience to emerging psychopathology., (© 2021 John Wiley & Sons Ltd.)

Introduction: How parents think and feel about their young children has implications for the parent-child relationship. We examined prospective associations between prenatal descriptions of the unborn child's personality and later parenting behavior., Methods: Pregnant women (N = 120; mean age = 26.16, SD = 5.71) were recruited in their third trimester for a longitudinal study. The sample is demographically diverse and predominantly economically disadvantaged. During prenatal interviews, women described their unborn child's personality, from which positive and negative emotion words were coded. Parenting behavior was coded 12 months postpartum (n = 105 for longitudinal analyses)., Results: Use of positive and negative words was negatively correlated (r = -.34, p < .001). Greater use of positive words to describe the unborn child's personality was associated with higher observed sensitivity, warmth, and engagement during mother-infant interactions, whereas negative words were associated with higher interference and lower levels of sensitivity. Mothers who used anxiety- and/or anger-related words to describe their unborn child, relative to mothers who did not, demonstrated higher interference and lower warmth and sensitivity., Conclusion: Descriptions of a child's personality before the child is born were associated with postnatal parenting behavior. Prenatal interventions that address negative thoughts and feelings regarding the child may be beneficial for promoting positive parenting postnatally., (© 2021 Michigan Association for Infant Mental Health.)

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., (© 2020 Association for Child and Adolescent Mental Health.)

Background: Despite being well-positioned to identify maltreatment in the children that they provide care for and being legally required to report suspected child maltreatment, early childhood professionals (ECPs) make a limited proportion of reports to child protective services. It is critical to identify evidence-based interventions to improve the reporting practices of this group of mandated reporters allowing for the better protection of children from maltreatment., Objective: The goal of the present study was to determine if iLookOut, an online child abuse identification and reporting training for ECPs, results in differential gains in knowledge and attitudes towards child abuse and its reporting among ECPs, as compared to an online standard training., Participants and Setting: Both interventions were completed online by participants recruited from licensed child care programs in Southern Maine from October 2017 to January 2020. Eligibility criteria included being at least 18 years of age, English-speaking, and working as paid or volunteer staff at a licensed child care program taking care of children 5 years of age or younger. Of the 1152 enrolled individuals, 1094 provided complete pre- and post-intervention data., Methods: A randomized controlled trial comparing iLookOut with an online standard training., Results: ECPs who completed iLookOut significantly outperformed those who completed Standard mandated reporter training in terms of both knowledge (d=1.09 vs. 0.67) and attitudes (d=0.67 vs. 0.54) relative to pre-test scores., Conclusions: iLookOut is a promising candidate for widespread use in meeting the need for evidence-based training on child abuse and its reporting., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: We examined the association between breastfeeding difficulties and trajectories of bonding in the first 6 months postpartum., Methods: Each month for the first 6 months following birth, 121 mothers of newborn infants (age = 23-45 years, M = 32.31 ± 4.79, 57% White, 23% Asian, 11% Hispanic, 9% Multiracial, 1% Black/African American) were invited to complete self-assessments of bonding. At the first postpartum assessment, mothers who intended to breastfeed also reported whether breastfeeding was more difficult than they had anticipated. We conducted linear mixed modelling to test whether early breastfeeding difficulty was associated with bonding trajectories and examined whether effects remained when accounting for postnatal depression symptoms., Results: We found main effects of breastfeeding difficulty (β = - .20, 95% CI [ -  .34, - .06]) and postpartum month (β = .13, 95% CI [.07, .20]) on bonding. On average, women who reported breastfeeding difficulty reported lower bonding than women who did not (Cohen's d = - 0.44, 95% CI [- 0.81, - 0.06]). Additional analyses indicated that, independent of breastfeeding difficulties, women who reported higher postnatal depressive symptoms across the first 6 months postpartum reported lower levels of bonding, on average. Further, within-individual decreases in postnatal depressive symptoms across the first six months were associated with relative improvements in bonding across this period., Conclusions for Practice: Our findings suggest that mothers who experience breastfeeding difficulties are at risk for reduced bonding with their infants in the first 6 months after birth. Moreover, while postnatal depressive symptoms are also associated with reduced bonding, the effect of breastfeeding difficulties on bonding persists over and above the effect of postnatal depressive symptoms.

To better understand early brain development in health and disorder, it is critical to accurately segment infant brain magnetic resonance (MR) images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF). Deep learning-based methods have achieved state-of-the-art performance; h owever, one of the major limitations is that the learning-based methods may suffer from the multi-site issue, that is, the models trained on a dataset from one site may not be applicable to the datasets acquired from other sites with different imaging protocols/scanners. To promote methodological development in the community, the iSeg-2019 challenge (http://iseg2019.web.unc.edu) provides a set of 6-month infant subjects from multiple sites with different protocols/scanners for the participating methods. T raining/validation subjects are from UNC (MAP) and testing subjects are from UNC/UMN (BCP), Stanford University, and Emory University. By the time of writing, there are 30 automatic segmentation methods participated in the iSeg-2019. In this article, 8 top-ranked methods were reviewed by detailing their pipelines/implementations, presenting experimental results, and evaluating performance across different sites in terms of whole brain, regions of interest, and gyral landmark curves. We further pointed out their limitations and possible directions for addressing the multi-site issue. We find that multi-site consistency is still an open issue. We hope that the multi-site dataset in the iSeg-2019 and this review article will attract more researchers to address the challenging and critical multi-site issue in practice.

Although decades of research have shown associations between early caregiving adversity, stress physiology and limbic brain volume (e.g., amygdala, hippocampus), the developmental trajectories of these phenotypes are not well characterized. In the current study, we used an accelerated longitudinal design to assess the development of stress physiology, amygdala, and hippocampal volume following early institutional care. Previously Institutionalized (PI; N = 93) and comparison (COMP; N = 161) youth (ages 4-20 years old) completed 1-3 waves of data collection, each spaced approximately 2 years apart, for diurnal cortisol (N = 239) and structural MRI (N = 156). We observed a developmental shift in morning cortisol in the PI group, with blunted levels in childhood and heightened levels in late adolescence. PI history was associated with reduced hippocampal volume and reduced growth rate of the amygdala, resulting in smaller volumes by adolescence. Amygdala and hippocampal volumes were also prospectively associated with future morning cortisol in both groups. These results indicate that adversity-related physiological and neural phenotypes are not stationary during development but instead exhibit dynamic and interdependent changes from early childhood to early adulthood., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Maternal depression is prevalent during and following pregnancy and is related to adverse outcomes in offspring. Perinatal depression is associated with risk for difficulties in offspring; however, the mechanisms underlying this association are not clear. We examined whether maternal prenatal and postnatal depressive symptoms were associated with infant white matter organization and with behavioral problems in toddlerhood., Methods: 37 mother-infant dyads (20 male; ages 5.95-7.66 months) participated in this study. We conducted diffusion MRI with infants during natural sleep. Mothers reported on their prenatal and postnatal depressive symptoms at six months postpartum. We calculated fractional anisotropy (FA), radial, axial, and mean diffusivity, and assessed offspring behavioral problems at age 18 months., Results: Prenatal depressive symptoms were associated with FA of the corpus callosum; postnatal depressive symptoms were not associated with FA of limbic tracts or corpus callosum segmentations. Higher levels of prenatal depressive symptoms were associated with higher FA and lower radial diffusivity of the corpus callosum genu; FA of this region was positively associated with behavioral problems at age 18 months., Limitations: This study had a small sample size; therefore, findings should be replicated. Further, we used retrospective reports of maternal prenatal depression, but validated them in this study., Conclusions: Depressive symptoms during pregnancy may affect infant corpus callosum development and, in turn, offspring behaviors. These findings suggest that early maternal stress accelerates infant neurodevelopment in a manner that may increase risk for behavioral problems. Thus, efforts to reduce maternal prenatal depression should be a public health priority., (Copyright © 2020. Published by Elsevier B.V.)

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.

The quantity and quality of the language input that infants receive from their caregivers affects their future language abilities; however, it is unclear how variation in this input relates to preverbal brain circuitry. The current study investigated the relation between naturalistic language input and the functional connectivity (FC) of language networks in human infancy using resting-state functional magnetic resonance imaging (rsfMRI). We recorded the naturalistic language environments of five- to eight-month-old male and female infants using the Linguistic ENvironment Analysis (LENA) system and measured the quantity and consistency of their exposure to adult words (AWs) and adult-infant conversational turns (CTs). Infants completed an rsfMRI scan during natural sleep, and we examined FC among regions of interest (ROIs) previously implicated in language comprehension, including the auditory cortex, the left inferior frontal gyrus (IFG), and the bilateral superior temporal gyrus (STG). Consistent with theory of the ontogeny of the cortical language network (Skeide and Friederici, 2016), we identified two subnetworks posited to have distinct developmental trajectories: a posterior temporal network involving connections of the auditory cortex and bilateral STG and a frontotemporal network involving connections of the left IFG. Independent of socioeconomic status (SES), the quantity of CTs was uniquely associated with FC of these networks. Infants who engaged in a larger number of CTs in daily life had lower connectivity in the posterior temporal language network. These results provide evidence for the role of vocal interactions with caregivers, compared with overheard adult speech, in the function of language networks in infancy., (Copyright © 2021 the authors.)

Knowledge and understanding about the impact of cumulative adverse experiences on the health and wellbeing of children, adolescents, and adults has rapidly expanded over the past 30 years. Despite the invaluable attention and support this proliferation has drawn to the importance of early childhood experiences, we believe that it is time to move beyond broad indices of risk and toward more specific and individualized understanding of how risk exposures are linked to clinical outcomes in young children. Within infant and early childhood mental health, there is a need for greater specificity in linking adverse caregiving experiences in early life to psychopathology in children. We highlight a framework distinguishing experiences of trauma from experiences of deprivation and use the examples of posttraumatic stress disorder and reactive attachment disorder to demonstrate how greater specificity in our understanding of early adverse caregiving can lead to more accurate and targeted diagnosis and treatment for young children. Both researchers and clinicians benefit from an approach to gain a greater appreciation of the links between specific types of experiences and outcomes in the children that we serve., (© 2020 Michigan Association for Infant Mental Health.)

Background: The quality of early caregiving experiences is a known contributor to the quality of the language experiences young children receive. What is unknown is whether, and if so, how psychosocial deprivation early in life is associated with long-lasting receptive language outcomes., Methods: Two prospective longitudinal studies examining early psychosocial deprivation/neglect in different contexts (i.e., deprivation due to institutional care or deprivation experienced by children residing within US families) and receptive language as assessed via the Peabody Picture Vocabulary Test (PPVT) were used to assess the magnitude of these associations. First, 129 participants from the Bucharest Early Intervention Project, a randomized controlled trial of foster care as an alternative to institutional care in Romania, completed a receptive language assessment at age 18 years. Second, from the USA, 3342 participants from the Fragile Families and Child Wellbeing Study were assessed from infancy until middle childhood., Results: Children exposed to early institutional care, on average, had lower receptive language scores than their never institutionalized counterparts in late adolescence. While randomization to an early foster care intervention had no long-lasting association with PPVT scores, the duration of childhood exposure to institutional care was negatively associated with receptive language. Psychosocial deprivation in US families was also negatively associated with receptive language longitudinally, and this association remained statistically significant even after accounting for measures of socioeconomic status., Conclusion: Experiences of psychosocial deprivation may have long-lasting consequences for receptive language ability, extending to age 18 years. Psychosocial deprivation is an important prospective predictor of poorer receptive language., Trial Registration: Bucharest Early Intervention Project ClinicalTrials.gov Identifier: NCT00747396.

Objective: Several studies have found associations between a diagnosis or symptoms of major depressive disorder and markers of cellular aging and dysfunction. These investigations, however, are predominantly cross-sectional and focus on adults. In the present study, we used a prospective longitudinal design to test the cross-sectional association between depressive symptoms in adolescents and telomere length (TL) as well as mitochondrial DNA copy number (mtDNA-cn)., Method: A total of 121 adolescents (mean age = 11.38 years, SD = 1.03; 39% male adolescents and 61% female adolescents) were followed for approximately 2 years. At baseline and follow-up, participants provided saliva for DNA extraction, from which measures of TL and mtDNA-cn were obtained. Depressive symptoms were obtained via the Children's Depression Inventory., Results: There was no association between depressive symptoms and markers of cellular aging at baseline; however, depressive symptoms at baseline predicted higher rates of telomere erosion (β = -0.201, p = .016) and greater increases in mtDNA-cn (β = 0.190, p = .012) over the follow-up period. Markers of cellular aging at baseline did not predict subsequent changes in depressive symptoms. Furthermore, including the number of stressful life events did not alter these patterns of findings., Conclusion: These results indicate that depressive symptoms precede changes in cellular aging and dysfunction, rather than the reverse., (Copyright © 2019 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

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).

Humans develop in the context of environmental information that can be considered either experience-expectant or experience-dependent. Though the exact timing of sensitive period closures and consequences of environmental experiences have not been well delineated, early life is a period of increased vulnerability. While some forms of care (e.g., institutional care for children; representing the absence of experience-expectant caregiving) are not present in the evolutionary history of humans, it is likely that what is considered significant hardship today may have been more typical experience-dependent environmental information in the evolutionary timescale. Thus, assumptions that threatening or neglectful experiences are unexpected for the human child may not fit well in the scope of the broader timescale of human history. We argue that it is important to consider early caregiving experiences from the context of what has been expected in our evolutionary past rather than what is expected in modern sociocultural terms., Competing Interests: Declarations of interest: none

Stressful experiences are linked to neurodevelopment. There is growing interest in the role of stress in the connectivity between the amygdala and medial prefrontal cortex (mPFC), a circuit that subserves automatic emotion regulation. However, the specific timing and mechanisms that underlie the association between stress and amygdala-mPFC connectivity are unclear. Many factors, including variations in fetal exposure to maternal stress, appear to affect early developing brain circuitry. However, few studies have examined the associations of stress and amygdala-mPFC connectivity in early life, when the brain is most plastic and sensitive to environmental influence. In this longitudinal pilot study, we characterized the association between prenatal stress and amygdala-mPFC connectivity in young infants (approximately age 5 weeks). A final sample of 33 women who provided data on preconception and prenatal stress during their pregnancy returned with their offspring for a magnetic resonance imaging scan session, which enabled us to characterize amygdala-mPFC structural and functional connectivity as a function of prenatal stress. Increased prenatal stress was associated with decreased functional connectivity and increased structural connectivity between the amygdala and mPFC. These results provide insight into the influence of prenatal maternal stress on the early development of this critical regulatory circuitry., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Pregnancy and the transition to parenthood is an important period marked by dramatic neurobiological and psychosocial changes that may have implications for the health of women and offspring. Although human and non-human animal research suggests that the brain undergoes alterations during the peripartum period, these changes are poorly understood. Here, we review existing research, particularly human neuroimaging and psychophysiological research, to examine changes in brain structure and function during the peripartum period and discuss potential implications for the health of women and offspring. First, we discuss the potential causes of these changes across pregnancy, including physiological and psychosocial factors. Next, we discuss the evidence for structural and functional changes in the brain during pregnancy and into the postpartum period, noting the need for research conducted prospectively across human pregnancy. Finally, we propose potential models of individual differences in peripartum neurobiological changes (i.e. hypo-response, typical response, hyper-response) and emphasize the need to consider trajectories of change in addition to pre-existing factors that may predict maternal adjustment to parenthood. We suggest that the consideration of individual differences in neurobiological trajectories across pregnancy may contribute to a better understanding of risk for negative health and behavior outcomes for women and offspring., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Socioeconomic status (SES), often conceptualized as income, education, or occupation, is associated with risk for disease morbidity and psychopathology. Recent research has focused on the potential biological mechanisms linking lower SES and poor outcomes; much of this work has examined the relationship between SES and markers of systemic inflammation. The strength of the estimated association between SES and inflammatory markers varies widely across individual studies. Thus, we used meta-analytic techniques to quantify the magnitude of this relationship. To accomplish this, PubMed and PsycINFO were searched for papers that reported on SES and two commonly measured systemic inflammatory markers, C-reactive protein (CRP) and interleukin-6 (IL-6). Peer-reviewed, empirical papers conducted in non-patient populations were included. Data from 43 papers (N = 111,156) reporting a total of 63 relevant effect sizes were included in analyses. SES, broadly defined, was significantly associated with both levels of CRP (Z = 0.12; 95% CI, 0.09-0.16) and IL-6 (Z = 0.15; 95% CI, 0.12-0.18); individuals with lower SES showed higher levels of systemic inflammation. Subanalyses demonstrated that studies operationalizing SES as either levels of income or educational attainment also found significant associations with both CRP and IL-6. Moderator analyses revealed that effect sizes varied based on sample characteristics and analysis approaches. Lower SES is associated with significantly elevated levels of inflammatory markers of disease risk. Thus, pro-inflammatory pathways are likely an important mechanism translating socioeconomic inequalities into mental and physical health disparities.

Infancy is marked by rapid neural and emotional development. The relation between brain function and emotion in infancy, however, is not well understood. Methods for measuring brain function predominantly rely on the BOLD signal; however, interpretation of the BOLD signal in infancy is challenging because the neuronal-hemodynamic relation is immature. Regional cerebral blood flow (rCBF) provides a context for the infant BOLD signal and can yield insight into the developmental maturity of brain regions that may support affective behaviors. This study aims to elucidate the relations among rCBF, age, and emotion in infancy. One hundred and seven mothers reported their infants' (infant age M ± SD = 6.14 ± 0.51 months) temperament. A subsample of infants completed MRI scans, 38 of whom produced usable perfusion MRI during natural sleep to quantify rCBF. Mother-infant dyads completed the repeated Still-Face Paradigm, from which infant affect reactivity and recovery to stress were quantified. We tested associations of infant age at scan, temperament factor scores, and observed affect reactivity and recovery with voxel-wise rCBF. Infant age was positively associated with CBF in nearly all voxels, with peaks located in sensory cortices and the ventral prefrontal cortex, supporting the formulation that rCBF is an indicator of tissue maturity. Temperamental Negative Affect and recovery of positive affect following a stressor were positively associated with rCBF in several cortical and subcortical limbic regions, including the orbitofrontal cortex and inferior frontal gyrus. This finding yields insight into the nature of affective neurodevelopment during infancy. Specifically, infants with relatively increased prefrontal cortex maturity may evidence a disposition toward greater negative affect and negative reactivity in their daily lives yet show better recovery of positive affect following a social stressor., (© 2019 John Wiley & Sons Ltd.)

Deviations in neurodevelopment may underlie the association between lower childhood socioeconomic status and difficulties in cognitive and socioemotional domains. Most previous investigations of the association between childhood socioeconomic status and brain morphology have used cross-sectional designs with samples that span wide age ranges, occluding effects specific to adolescence. Sex differences in the association between socioeconomic status and neurodevelopment may emerge or intensify during adolescence. In a sample representative of the San Francisco Bay Area, we used whole-brain tensor-based morphometry to examine sex differences in the cross-sectional association between variation in family income-to-needs ratio (INR) and cortical and subcortical gray and white matter volume during early adolescence (ages 9-13 years; N = 147), as well as in the longitudinal association between INR and change in volume from early to later adolescence (ages 11-16 years, N = 109). Biological sex interacted with INR to explain variation in volume in several areas cross-sectionally and longitudinally. Effects were primarily in cortical gray matter areas, including regions of the association cortex and sensorimotor processing areas. Effect sizes tended to be larger in boys than in girls. Biological sex may be an important variable to consider in analyses of the effects of family income on structural neurodevelopment during adolescence., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Early life stress (ELS) is associated with increased risk for the development of major depressive disorder (MDD) in adulthood; however, the degree to which ELS is associated with an early onset of MDD (ie, during childhood or adolescence) is not known. In this meta-analysis, we estimated the associations between ELS and the risk for onset of MDD before age 18 years. In addition, we examined the associations between eight specific forms of ELS (ie, sexual abuse, physical abuse, poverty, physical illness/injury, death of a family member, domestic violence, natural disaster, and emotional abuse) and risk for youth-onset MDD., Method: We conducted a systematic search in scientific databases for studies that assessed both ELS and the presence or absence of MDD before age 18 years. We identified 62 journal articles with a total of 44,066 unique participants. We assessed study quality using the Newcastle-Ottawa Scale. When heterogeneous effect sizes were detected, we tested whether demographic and/or methodological factors moderated the association between ELS and MDD., Results: Using a random-effects meta-analysis, we found that individuals who experienced ELS were more likely to develop MDD before the age of 18 years than were individuals without a history of ELS (odds ratio = 2.50; 95% confidence interval 2.08, 3.00). Separate meta-analyses revealed a range of associations with MDD: whereas some types of ELS (eg, poverty) were not associated with MDD, other types (eg, emotional abuse) were associated more strongly with MDD than was ELS considered more broadly., Conclusion: These findings provide important evidence that the adverse effect of ELS on MDD risk manifests early in development, prior to adulthood, and varies by type of ELS., (Copyright © 2019 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Background: There are significant sex differences in human physiology and disease; the genomic sources of these differences, however, are not well understood. During puberty, a drastic neuroendocrine shift signals physical changes resulting in robust sex differences in human physiology. Here, we explore how shifting patterns of DNA methylation may inform these pathways of biological plasticity during the pubertal transition. In this study we analyzed DNA methylation (DNAm) in saliva at two time points across the pubertal transition within the same individuals. Our purpose was to compare two domains of DNAm patterns that may inform processes of sexual differentiation 1) sex related sites, which demonstrated differences between males from females and 2) time related sites in which DNAm shifted significantly between timepoints. We further explored the correlated network structure sex and time related DNAm networks and linked these patterns to pubertal stage, assays of salivary testosterone, a reliable diagnostic of free, unbound hormone that is available to act on target tissues, and overlap with androgen response elements., Results: Sites that differed by biological sex were largely independent of sites that underwent change across puberty. Time-related DNAm sites, but not sex-related sites, formed correlated networks that were associated with pubertal stage. Both time and sex DNAm networks reflected salivary testosterone levels that were enriched for androgen response elements, with sex-related DNAm networks being informative of testosterone levels above and beyond biological sex later in the pubertal transition., Conclusions: These results inform our understanding of the distinction between sex- and time-related differences in DNAm during the critical period of puberty and highlight a novel linkage between correlated patterns of sex-related DNAm and levels of salivary testosterone.

Early life stress (ELS) may accelerate frontoamygdala development related to socioemotional processing, serving as a potential source of resilience. Whether this circuit is associated with other proposed measures of accelerated development is unknown. In a sample of young adolescents, we examined the relations among ELS, frontoamygdala circuitry during viewing of emotional faces, cellular aging as measured by telomere shortening, and pubertal tempo. We found that greater cumulative severity of ELS was associated with stronger negative coupling between bilateral centromedial amygdala and the ventromedial prefrontal cortex, a pattern that may reflect more mature connectivity. More negative frontoamygdala coupling (for distinct amygdala subdivisions) was associated with slower telomere shortening and pubertal tempo over 2 years. These potentially protective associations of negative frontoamygdala connectivity were most pronounced in adolescents who had been exposed to higher ELS. Our findings provide support for the formulation that ELS accelerates maturation of frontoamygdala connectivity and provide novel evidence that this neural circuitry confers protection against accelerated biological aging, particularly for adolescents who have experienced higher ELS. Although negative frontoamygdala connectivity may be an adaptation to ELS, frontoamygdala connectivity, cellular aging, and pubertal tempo do not appear to be measures of the same developmental process., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: Researchers have documented that child maltreatment is associated with adverse long-term consequences for mental health, including increased risk for depression. Attempts to conduct meta-analyses of the association between different forms of child maltreatment and depressive symptomatology in adulthood, however, have been limited by the wide range of definitions of child maltreatment in the literature., Objective: We sought to meta-analyze a single, widely-used dimensional measure of child maltreatment, the Childhood Trauma Questionnaire, with respect to depression diagnosis and symptom scores., Participants and Setting: 192 unique samples consisting of 68,830 individuals., Methods: We explored the association between total scores and scores from specific forms of child maltreatment (i.e., emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect) and depression using a random-effects meta-analysis., Results: We found that higher child maltreatment scores were associated with a diagnosis of depression (g = 1.07; 95 % CI, 0.95-1.19) and with higher depression symptom scores (Z = .35; 95 % CI, .32-.38). Moreover, although each type of child maltreatment was positively associated with depression diagnosis and scores, there was variability in the size of the effects, with emotional abuse and emotional neglect demonstrating the strongest associations., Conclusions: These analyses provide important evidence of the link between child maltreatment and depression, and highlight the particularly larger association with emotional maltreatment in childhood., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Studying offspring of depressed mothers is a promising strategy for elucidating factors that contribute to depression onset, given that these offspring are three to six times more likely to develop depression than are their low-risk peers. In this paper we briefly describe representative findings from studies of younger and older offspring of depressed mothers and identify factors that have garnered the most consistent empirical support across development. We discuss what these studies can and cannot tell us about mechanisms that might underlie the intergenerational transmission of risk for depression, regardless of the age of offspring being studied. Finally, in light of limitations of this literature, we offer recommendations for future research.

Background: While depression is typically associated with reduced levels of empathy, this association differs depending on how empathy is measured. Given the importance of empathy in the parent-child relationship, we sought to examine whether the associations between depression and dispositional empathy would also extend to empathy towards one's own child., Methods: Within a non-clinical sample of 150 parents of young children, we examined the associations between self-reported depressive symptoms, dispositional empathic tendencies, and empathy specifically toward their own children, and how these associations might differ based on parent gender., Results: Depressive symptoms were related to lower levels of cognitive and affective empathy, and higher levels of empathic distress. Over and above the association with dispositional empathy, depressive symptoms were associated with reduced levels of parents' affective empathy toward their own child. The associations between depressive symptoms and both dispositional and own-child specific empathy varied by parent gender. For fathers, depressive symptoms predicted own-child specific affective empathy, over and above dispositional affective empathy, while for mothers, depressive symptoms predicted own-child specific empathic distress, over and above dispositional empathic distress., Conclusions: The current findings provide further indication that caregivers with elevated depression may engage in patterns of thoughts and behaviors that have implications for their interactions with their children. Parents' experienced empathy toward their own child may be one mechanism by which depression impacts the early caregiving environment, and thus may be an important target for intervention in improving the early caregiving experiences for children at elevated risk due to parental depression. Differences in cognitive and affective empathy found among those with depression may be even more pronounced in the thoughts and feelings towards one's own child, making this an important clinical target., Competing Interests: The authors have declared that no competing interests exist.

Early life adversity and insecure attachment style are known risk factors for perinatal depression. The biological pathways linking these experiences, however, have not yet been elucidated. We hypothesized that overlap in patterns of DNA methylation in association with each of these phenomena could identify genes and pathways of importance. Specifically, we wished to distinguish between allostatic-load and role-transition hypotheses of perinatal depression. We conducted a large-scale analysis of methylation patterns across 5 × 10 6 individual CG dinucleotides in 54 women participating in a longitudinal prospective study of perinatal depression, using clustering-based criteria for significance to control for multiple comparisons. We identified 1580 regions in which methylation density was associated with childhood adversity, 3 in which methylation density was associated with insecure attachment style, and 6 in which methylation density was associated with perinatal depression. Shorter telomeres were observed in association with childhood trauma but not with perinatal depression or attachment insecurity. A detailed analysis of methylation density in the oxytocin receptor gene revealed similar patterns of DNA methylation in association with perinatal depression and with insecure attachment style, while childhood trauma was associated with a distinct methylation pattern in this gene. Clinically, attachment style was strongly associated with depression only in pregnancy and the early postpartum, whereas the association of childhood adversity with depression was time-invariant. We concluded that the broad DNA methylation signature and reduced telomere length associated with childhood adversity could indicate increased allostatic load across multiple body systems, whereas perinatal depression and attachment insecurity may be narrower phenotypes with more limited DNA methylation signatures outside the CNS, and no apparent association with telomere length or, by extension, allostatic load. In contrast, the finding of matching DNA methylation patterns within the oxytocin receptor gene for perinatal depression and attachment insecurity is consistent with the theory that the perinatal period is a time of activation of existing attachment schemas for the purpose of structuring the mother-child relationship, and that such activation may occur in part through specific patterns of methylation of the oxytocin receptor gene.

Gastrointestinal and mental disorders are highly comorbid, and animal models have shown that both can be caused by early adversity (e.g., parental deprivation). Interactions between the brain and bacteria that live within the gastrointestinal system (the microbiome) underlie adversity-gastrointestinal-anxiety interactions, but these links have not been investigated during human development. In this study, we utilized data from a population of 344 youth (3-18 years old) who were raised with their biological parents or were exposed to early adverse caregiving experiences (i.e., institutional or foster care followed by international adoption) to explore adversity-gastrointestinal-anxiety associations. In Study 1, we demonstrated that previous adverse care experiences were associated with increased incidence of gastrointestinal symptoms in youth. Gastrointestinal symptoms were also associated with concurrent and future anxiety (measured across 5 years), and those gastrointestinal symptoms mediated the adversity-anxiety association at Time 1. In a subsample of children who provided both stool samples and functional magnetic resonance imaging of the brain (Study 2, which was a "proof-of-principle"), adversity was associated with changes in diversity (both alpha and beta) of microbial communities, and bacteria levels (adversity-associated and adversity-independent) were correlated with prefrontal cortex activation to emotional faces. Implications of these data for supporting youth mental health are discussed.

The stress response system is disrupted in individuals with major depressive disorder (MDD) as well as in those at elevated risk for developing MDD. We examined whether DNA methylation (DNAm) levels of CpG sites within HPA-axis genes predict the onset of MDD. Seventy-seven girls, approximately half (n = 37) of whom were at familial risk for MDD, were followed longitudinally. Saliva samples were taken in adolescence (M age = 13.06 years [SD = 1.52]) when participants had no current or past MDD diagnosis. Diagnostic interviews were administered approximately every 18 months until the first onset of MDD or early adulthood (M age of last follow-up = 19.23 years [SD = 2.69]). We quantified DNAm in saliva samples using the Illumina EPIC chip and examined CpG sites within six key HPA-axis genes (NR3C1, NR3C2, CRH, CRHR1, CRHR2, FKBP5) alongside 59 genotypes for tagging SNPs capturing cis genetic variability. DNAm levels within CpG sites in NR3C1, CRH, CRHR1, and CRHR2 were associated with risk for MDD across adolescence and young adulthood. To rule out the possibility that findings were merely due to the contribution of genetic variability, we re-analyzed the data controlling for cis genetic variation within these candidate genes. Importantly, methylation levels in these CpG sites continued to significantly predict the onset of MDD, suggesting that variation in the epigenome, independent of proximal genetic variants, prospectively predicts the onset of MDD. These findings suggest that variation in the HPA axis at the level of the methylome may predict the development of MDD.

Early institutional rearing is associated with increased risk for subsequent peer relationship difficulties, but the underlying mechanisms have not been identified. Friendship characteristics, social behaviors with peers, normed assessments of social problems, and social cue use were assessed in 142 children (mean age = 10.06, SD = 2.02; range 7-13 years), of whom 67 were previously institutionalized (PI), and 75 were raised by their biological families. Anxiety and attention-deficit/hyperactivity disorder (ADHD) symptoms, often elevated among PI children, were examined as potential mediators of PI status and baseline social functioning and longitudinal follow-ups (2 and 4 years later). Twenty-seven percent of PI children fell above the Child Behavior Checklist Social Problems cutoff. An examination of specific social behaviors with peers indicated that PI and comparison children did not differ in empathic concern or peer social approach, though parents were more likely to endorse aggression/overarousal as a reason that PI children might struggle with friendships. Comparison children outperformed PI children in computerized testing of social cue use learning. Finally, across these measures, social difficulties exhibited in the PI group were mediated by ADHD symptoms with predicted social problems assessed 4 years later. These findings show that, when PI children struggle with friendships, mechanisms involving attention and behavior regulation are likely contributors.

Psychosocial deprivation is associated with the development of socially aberrant behaviors, including signs of disinhibited social engagement disorder (DSED). In longitudinal studies, signs of DSED have been shown to decrease over time, especially as children are removed from conditions of deprivation. What is less clear is whether signs of DSED in early childhood are associated with poorer functioning in early adolescence, including among children who no longer manifest signs of DSED at this age. In a sample of 136 Romanian children from the Bucharest Early Intervention Project (BEIP), who were exposed to early psychosocial deprivation in the form of institutional care, we examined caregiver-reported (ages 30, 42, and 54 months and 12 years) and observer-rated (age 54 months) signs of DSED. Competent functioning in early adolescence (age 12 years) was assessed across seven domains (i.e., family relationships, peer relationships, academic performance, physical health, mental health, substance use, and risk-taking behavior). A diagnosis of DSED in early childhood was associated with reduced competence in early adolescence. Furthermore, this association was significant even when signs of DSED diminished by age 12 years. We conclude that signs of DSED in early life are associated with reduced likelihood of competent functioning many years later in adolescence, even if signs of the disorder remit.

Irritability is a common feature of many psychiatric disorders, including both externalizing and internalizing disorders. There is little research, however, examining associations between irritability and these symptom domains, particularly during the important developmental period of adolescence, characterized by sex differences in the prevalence of disorders. We examined the cross-sectional associations between irritability, measured with the Affective Reactivity Index, and symptoms of externalizing and internalizing domains of psychopathology, measured with the Youth Self Report, in a volunteer community sample ( N = 183) of 9- to 13-year-old ( M  = 11.39, SD  = 1.07) boys and girls (37% White/Caucasian, 8% Asian, 11% Hispanic, 8% African American, 2% Native American, 2% Pacific Islander, 28% Other, and 3% not reported). A subset of the sample ( n  = 112) provided data at a 2-year follow-up, used to extend these associations. There were no sex differences in levels of irritability; however, the associations between irritability and symptom domains were moderated by sex. Specifically, in girls, irritability was associated equally with externalizing and internalizing symptoms. In contrast, in boys, irritability was associated more strongly with externalizing symptoms than with internalizing symptoms. Thus, across both sexes, irritability was moderately associated with externalizing symptoms, but the association between irritability and internalizing symptoms was stronger in girls than in boys. At follow-up, sex moderated the association between baseline irritability and later externalizing and internalizing symptoms. These findings indicate that irritability is associated with both externalizing and internalizing symptoms in early adolescence and that irritability is associated with internalizing symptoms more strongly in girls than in boys.

Early life stress (ELS) is a risk factor for the development of depression in adolescence; the mediating neurobiological mechanisms, however, are unknown. In this study, we examined in early pubertal youth the associations among ELS, cortisol stress responsivity, and white matter microstructure of the uncinate fasciculus and the fornix, two key frontolimbic tracts; we also tested whether and how these variables predicted depressive symptoms in later puberty. A total of 208 participants (117 females; M age = 11.37 years; M Tanner stage = 2.03) provided data across two or more assessment modalities: ELS; salivary cortisol levels during a psychosocial stress task; diffusion magnetic resonance imaging; and depressive symptoms. In early puberty there were significant associations between higher ELS and decreased cortisol production, and between decreased cortisol production and increased fractional anisotropy in the uncinate fasciculus. Further, increased fractional anisotropy in the uncinate fasciculus predicted higher depressive symptoms in later puberty, above and beyond earlier symptoms. In post hoc analyses, we found that sex moderated several additional associations. We discuss these findings within a broader conceptual model linking ELS, emotion dysregulation, and depression across the transition through puberty, and contend that brain circuits implicated in the control of hypothalamic-pituitary-adrenal axis function should be a focus of continued research.

Irritability is garnering increasing attention in psychiatric research as a transdiagnostic marker of both internalizing and externalizing disorders. These disorders often emerge during adolescence, highlighting the need to examine changes in the brain and in psychological functioning during this developmental period. Adolescents were recruited for a longitudinal study examining the effects of early life stress on the development of psychopathology. The 151 adolescents (73 M/78 F, average age = 11.5 years, standard deviation = 1.1) were scanned with a T1-weighted MRI sequence and parents completed reports of adolescent irritability using the Affective Reactivity Index. Of these 151 adolescents, 94 (46 M/48 F) returned for a second session (average interval = 1.9 years, SD = 0.4). We used tensor-based morphometry to examine cross-sectional and longitudinal associations between irritability and regional brain volume. Irritability was associated with brain volume across a number of regions. More irritable individuals had larger hippocampi, insula, medial orbitofrontal cortex and cingulum/cingulate cortex and smaller putamen and internal capsule. Across the brain, more irritable individuals also had larger volume and less volume contraction in a number of areas that typically decrease in volume over the developmental period studied here, suggesting delayed maturation. These structural changes may increase adolescents' vulnerability for internalizing and externalizing disorders., (© The Author(s) 2019. Published by Oxford University Press.)

Background: The human brain remains highly plastic for a protracted developmental period. Thus, although early caregiving adversities that alter amygdala development can result in enduring emotion regulation difficulties, these trajectories should respond to subsequent enriched caregiving. Exposure to high-quality parenting can regulate (i.e., decrease) children's amygdala reactivity, a process that, over the long term, is hypothesized to enhance emotion regulation. We tested the hypothesis that even following adversity, the parent-child relationship would be associated with decreases in amygdala reactivity to parent cues, which would in turn predict lower future anxiety., Methods: Participants were 102 children (6-10 years of age) and adolescents (11-17 years of age), for whom data were collected at one or two time points and who either had experienced institutional care before adoption (n = 45) or had lived always with their biological parents (comparison; n = 57). We examined how amygdala reactivity to visual cues of the parent at time 1 predicted longitudinal change (from time 1 to time 2) in parent-reported child anxiety across 3 years., Results: At time 1, on average, amygdala reactivity decrements to parent cues were not seen in children who had received institutional care but were seen in children in the comparison group. However, some children who previously experienced institutional care did show decreased amygdala reactivity to parent cues (∼40%), which was associated with greater child-reported feelings of security with their parent. Amygdala decreases at time 1 were followed by steeper anxiety reductions from time 1 to time 2 (i.e., 3 years)., Conclusions: These data provide a neurobiological mechanism by which the parent-child relationship can increase resilience, even in children at significant risk for anxiety symptoms., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)