Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence.

Maltreatment during childhood is a major risk factor for anxiety and depression, which are major public health problems. However, the underlying brain mechanism linking maltreatment and internalizing disorders remains poorly understood. Maltreatment may alter the activation of fear circuitry, but little is known about its impact on the connectivity of this circuitry in adolescence and whether such brain changes actually lead to internalizing symptoms. We examined the associations between experiences of maltreatment during childhood, resting-state functional brain connectivity (rs-FC) of the amygdala and hippocampus, and internalizing symptoms in 64 adolescents participating in a longitudinal community study. Childhood experiences of maltreatment were associated with lower hippocampus-subgenual cingulate rs-FC in both adolescent females and males and lower amygdala-subgenual cingulate rs-FC in females only. Furthermore, rs-FC mediated the association of maltreatment during childhood with adolescent internalizing symptoms. Thus, maltreatment in childhood, even at the lower severity levels found in a community sample, may alter the regulatory capacity of the brain's fear circuit, leading to increased internalizing symptoms by late adolescence. These findings highlight the importance of fronto-hippocampal connectivity for both sexes in internalizing symptoms following maltreatment in childhood. Furthermore, the impact of maltreatment during childhood on both fronto-amygdala and -hippocampal connectivity in females may help explain their higher risk for internalizing disorders such as anxiety and depression.

The impact of children's internalizing and externalizing problems on parenting: Transactional processes and reciprocal change over time.

Most theoretical models of developmental psychopathology involve a transactional, bidirectional relation between parenting and children's behavior problems. The present study utilized a cross-lagged panel, multiple interval design to model change in bidirectional relations between child and parent behavior across successive developmental periods. Two major categories of child behavior problems, internalizing and externalizing, and two aspects of parenting, positive (use of support and structure) and harsh discipline (use of physical punishment), were modeled across three time points spaced 3 years apart. Two successive developmental intervals, from approximately age 7.5 to 10.5 and from 10.5 to 13.5, were included. Mother-child dyads (N = 138; 65 boys) from a lower income longitudinal sample of families participated, with standardized measures of mothers rating their own parenting behavior and teachers reporting on child's behavior. Results revealed different types of reciprocal relations between specific aspects of child and parent behavior, with internalizing problems predicting an increase in positive parenting over time, which subsequently led to a reduction in internalizing problems across the successive 3-year interval. In contrast, externalizing predicted reduced levels of positive parenting in a reciprocal sequence that extended across two successive intervals and predicted increased levels of externalizing over time. Implications for prevention and early intervention are discussed.

A dual-axis approach to understanding neuroendocrine development.

This introduction sets out to present a series of paper about a novel perspective regarding stress and sex hormones, or what the authors within this special issue term "coupling" of hypothalamic-pituitary-adrenal and--gonadal axes. This view postulates that these axes do not necessarily operate in opposition, but can operate together as evidenced empirically as a positive within-person association between stress hormones like cortisol or sex hormones like testosterone. A wealth of papers within the special issue demonstrate positive coupling across acute, diurnal, basal, and longitudinal timeframes and across several different types of contexts. Reviews were meant to challenge whether this was physiologically plausible. Consistently, sophisticated statistical models were utilized in order to show a template for how to model positive coupling and to ensure that coupling was a within-person phenomenon. We cautiously considered positive coupling until the consistency of observing coupling was robust enough for us to consider challenging the prevailing oppositional view of these axes. We do so to acknowledge that there are contexts, moments and stages in which the function of these axes should work together: for example when contexts are both stressful and challenging or at developmental stages (like adolescence) in which the youth must grow up despite the storm and stress of youth. We hope that by putting forward a functional dual-axis approach, the field will be able to consider when and how these axes work together.

Within-person coupling of changes in cortisol, testosterone, and DHEA across the day in adolescents.

We comprehensively examined within-person and between-person associations between cortisol and DHEA and cortisol and testosterone across the day. Data are from a sample of 213 adolescents aged 11-16 (M = 13.7, SD = 1.5 years) from the Northeastern US who were oversampled for psychopathology symptoms. Six repeated measures of hormone levels across 3 days were used to test three specific questions of cortisol-DHEA and cortisol-testosterone associations within individuals (coupling) across the day, and one question of cortisol-DHEA and cortisol-testosterone diurnal slopes were associated between adolescents. Results consistently revealed positive cortisol-DHEA and cortisol-testosterone coupling across the day, often more pronounced in girls relative to boys. Cortisol and DHEA slopes were positively associated, whereas cortisol and testosterone were negatively associated between-adolescents. Findings suggest multiple mechanisms and highlight the multifaceted nature of associations of hormone changes during adolescence and importance of considering both axes for between- and within-person aspects of neuroendocrine development.

Neuroendocrine coupling across adolescence and the longitudinal influence of early life stress.

Drawing on conceptual models illustrating the advantages of a multisystemic, interactive, developmental approach to understanding development, the present study examines the covariation of stress and sex hormones across the adolescent transition and the effect of early life stress (ELS) on neuroendocrine coupling to gain insight into atypical development. Morning levels of cortisol, testosterone, and dehydroepiandrosterone (DHEA) were assessed at ages 11, 13, and 15; ELS was assessed during the infancy and preschool periods. Hierarchical linear modeling revealed that cortisol-DHEA coupling patterns progressed to tight, positive coupling across adolescence. Cortisol-testosterone coupling was positive at age 11 but became more negative at ages 13 and 15. Exposure to ELS resulted in more adultlike neuroendocrine coupling patterns earlier in life than non-exposed youth; however the effect of ELS on cortisol-testosterone coupling was unique to girls. Results illustrate trajectories of neuroendocrine coupling that may be unique to adolescence. Moderation by ELS suggests that early stress exposure may prompt earlier adultlike neuroendocrine coupling, particularly within girls, which may contribute to early pubertal development.

Developmental and contextual considerations for adrenal and gonadal hormone functioning during adolescence: Implications for adolescent mental health.

Substantial research has implicated the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes independently in adolescent mental health problems, though this literature remains largely inconclusive. Given the cross-talk between the HPA and HPG axes and their increased activation in adolescence, a dual-axis approach that examines both axes simultaneously is proposed to predict the emergence and persistence of adolescent mental health problems. After briefly orienting readers to HPA and HPG axis functioning, we review the literature examining associations between hormone levels and changes with behavior during adolescence. Then, we provide a review of the literature supporting examination of both axes simultaneously and present the limited research that has taken a dual-axis approach. We propose future directions including consideration of between-person and within-person approaches to address questions of correlated changes in HPA and HPG hormones. Potential moderators are considered to increase understanding of the nuanced hormone-behavior associations during key developmental transitions.

Adolescent internalizing symptoms and negative life events: the sensitizing effects of earlier life stress and cortisol.

Although adolescence is marked by increased negative life events and internalizing problems, few studies investigate this association as an ongoing longitudinal process. Moreover, while there are considerable individual differences in the degree to which these phenomena are linked, little is known about the origins of these differences. The present study examines early life stress (ELS) exposure and early-adolescent longitudinal afternoon cortisol level as predictors of the covariation between internalizing symptoms and negative life events across high school. ELS was assessed by maternal report during infancy, and the measure of cortisol was derived from assessments at ages 11, 13, and 15 years. Life events and internalizing symptoms were assessed at ages 15, 17, and 18 years. A two-level hierarchical linear model revealed that ELS and cortisol were independent predictors of the covariation of internalizing symptoms and negative life events. Compared to those with lower levels of ELS, ELS-exposed adolescents displayed tighter covariation between internalizing symptoms and negative life events. Adolescents with lower longitudinal afternoon cortisol displayed tighter covariation between negative life events and internalizing symptoms, while those with higher cortisol demonstrated weaker covariation, partially due to increased levels of internalizing symptoms when faced with fewer negative life events.

Longitudinal associations between infections and atopic disorders across childhood and dysregulated adrenocortical functioning in early adolescence.

The present study sought to determine if exposure to common childhood medical problems (i.e., infections and atopic disorders [e.g., allergies, asthma]) may dysregulate the hypothalamic-pituitary-adrenal (HPA) axis. Longitudinal data from 96 youth were used to examine this possibility. Medical records were drawn from government databases indicating the frequency of visits to healthcare facilities for infections and atopic disorders from infancy to early adolescence. During early adolescence, participants provided salivary cortisol samples from awakening until bedtime over 2 consecutive days. Individuals with a history of increased number visits for infections across childhood displayed elevated levels of cortisol at awakening whereas individuals with childhood histories of visits for atopic disorders displayed blunted diurnal cortisol slopes. These findings build on previous research documenting associations between infections and atopic disorders and cortisol by identifying longitudinal linkages from early health problems to later HPA axis functioning.

Cortisol's diurnal rhythm indexes the neurobiological impact of child adversity in adolescence.

Adverse early life experiences, such as child maltreatment, shapes hypothalamic-pituitary-adrenal (HPA) activity. The impact of social context is often probed through laboratory stress reactivity, yet child maltreatment is a severe form of chronic stress that recalibrates even stable or relatively inflexible stress systems such as cortisol's diurnal rhythm. This study was designed to determine how different social contexts, which place divergent demands on children, shape cortisol's diurnal rhythm. Participants include 120 adolescents (9-14 years), including 42 youth with substantiated child physical abuse. Up to 32 saliva samples were obtained in the laboratory, on days youth stayed home, and on school days. A 3-level hierarchical linear model examined cortisol within each day and extracted the diurnal rhythm at level 1; across days at level 2; and between-individual differences in cortisol and its rhythm at level 3. While cortisol's diurnal rhythm was flattened when youth were in the novel laboratory context, the impact of maltreatment was observed within the home context such that maltreated children had persistently flattened diurnal rhythms. The effect of maltreatment overlapped with current chronic interpersonal family stress. Results are consistent with the idea that maltreatment exerts a robust, detrimental impact on the HPA axis and are interpreted in the context of less flexibility and rhythmicity. The HPA axis adapts by encoding signifiers of relevant harsh or unpredictable environments, and the extreme stress of physical abuse in the family setting may be one of these environments which calibrates the developing child's stress responsive system, even throughout a developmental stage in which the family takes on diminishing importance.

Perception of neighborhood disorder and health service usage in a Canadian sample.

BACKGROUND: Neighborhood environment, both actual and perceived, is associated with health outcomes; however, much of this research has relied on self-reports of these outcomes. PURPOSE: The association between both perception of neighborhood disorder and neighborhood poverty (as measured by postal code socioeconomic status) was examined in the prediction of health service usage. METHOD: Participants in a longitudinal project were contacted in mid-adulthood regarding their perception of neighborhood disorder. Their census tract data and medical records were drawn from government databases. RESULTS: Higher perceived neighborhood disorder was significantly associated with higher levels of total health services usage, lifestyle illnesses, specialist visits, and emergency room visits, even when neighborhood poverty and individual-level variables were controlled for. Neighborhood poverty was only significantly associated with fewer total hospitalizations. CONCLUSIONS: Higher perceived neighborhood disorder was associated with higher rates of health service usage, suggesting further investigation into the mechanisms by which perceptions of the environment influences health outcomes.

Disentangling psychobiological mechanisms underlying internalizing and externalizing behaviors in youth: longitudinal and concurrent associations with cortisol.

Research examining cortisol dysregulation is seemingly contradictory with studies showing that both internalizing and externalizing behaviors are related to high and low cortisol. One extant theory to explain divergent findings in the stress literature is that both hypo- and hyper-arousal of the hypothalamic-pituitary-adrenal (HPA) axis may be present depending on time since onset of the stressor. This theory may extend to the onset of internalizing and externalizing behaviors. Data from 96 youth participating in a longitudinal project were used to examine this possibility. Composite measures of internalizing and externalizing behaviors at both childhood and early adolescence were formed using mother and teacher reports. Multiple salivary cortisol samples were also collected over two consecutive days during early adolescence. Problematic behaviors were associated with cortisol and the direction of the association was dependent on amount of time passed since onset of the behaviors. When examined concurrently in adolescence, youth with more internalizing behaviors had higher morning cortisol; however, when examined longitudinally, youth with more internalizing behaviors in childhood had lower morning cortisol levels as adolescents. Youth with more externalizing behaviors in childhood had flattened diurnal cortisol rhythms as adolescents, and this finding persisted when examined in adolescence. Cortisol dysregulation was greatest in children with the most severe behavior problems. Findings support the theoretical model of blunting of the HPA axis over time. While the HPA axis may show hyper-arousal when youth first display behaviors, long-term exposure may lead to a hypo-arousal of the HPA axis which culminates in a dysregulated diurnal rhythm.

Influence of early life stress on later hypothalamic-pituitary-adrenal axis functioning and its covariation with mental health symptoms: a study of the allostatic process from childhood into adolescence.

The hypothalamic-pituitary-adrenal (HPA) axis is a primary mechanism in the allostatic process through which early life stress (ELS) contributes to disease. Studies of the influence of ELS on children's HPA axis functioning have yielded inconsistent findings. To address this issue, the present study considers multiple types of ELS (maternal depression, paternal depression, and family expressed anger), mental health symptoms, and two components of HPA functioning (traitlike and epoch-specific activity) in a long-term prospective community study of 357 children. ELS was assessed during the infancy and preschool periods; mental health symptoms and cortisol were assessed at child ages 9, 11, 13, and 15 years. A three-level hierarchical linear model addressed questions regarding the influences of ELS on HPA functioning and its covariation with mental health symptoms. ELS influenced traitlike cortisol level and slope, with both hyper- and hypoarousal evident depending on type of ELS. Further, type(s) of ELS influenced covariation of epoch-specific HPA functioning and mental health symptoms, with a tighter coupling of HPA alterations with symptom severity among children exposed previously to ELS. Results highlight the importance of examining multiple types of ELS and dynamic HPA functioning in order to capture the allostatic process unfolding across the transition into adolescence.

Adrenocortical responses to strangers in preschoolers: relations with parenting, temperament, and psychopathology.

Previous research has provided inconsistent evidence for the relations between young children's hypothalamic-pituitary-adrenal (HPA) functioning and their temperament, parenting, and adjustment. Building biopsychosocial models of adjustment, we examined how temperamental inhibition and maternal punishment contributed to preschoolers' adrenocortical activity while interacting with adult strangers. We also examined whether HPA functioning moderated relations between dispositional and familial factors and children's internalizing and externalizing problems. A total of 402 preschool-aged children from three independent samples with parallel and overlapping measures were studied. Salivary cortisol levels were measured twice while interacting with adult strangers during testing protocols. Mothers reported on temperamental inhibition, maternal punishment and children's problems. Maternal punishment predicted higher cortisol levels 20 and 65 min after meeting adult strangers. Prolonged cortisol elevation was associated with having fewer externalizing problems. Boys who experienced more maternal punishment and had higher cortisol 20 min after meeting strangers manifested more externalizing problems. Girls who were more inhibited and had prolonged cortisol elevations had more internalizing problems. In accord with biopsychosocial models of psychopathology, HPA functioning in preschoolers was sensitive to variations in socialization experiences, and moderated children's risk for emotional and behavioral problems.

Hyper- and hypo-cortisol functioning in post-institutionalized adolescents: The role of severity of neglect and context.

Understanding the developmental timing of stress exposure may help inform mechanisms underlying how stress "gets under the skin" and influences the stress response system, including the HPA axis and its end-product cortisol. Early adversity may be particularly detrimental; however, it is difficult to disentangle the timing of adversity from its cumulative burden because there is typically high continuity between early and later adversity. Moreover, context and the different stressors inherent in various contexts may interact with stress exposure to influence psychophysiological functioning. To address this issue, we examined adolescents who had been reared in institutions and suffered neglect or social deprivation ranging from approximately six months to several years of life prior to adoption into U.S. homes. We focused on the stress hormone cortisol because it can reflect continued regulatory problems in youth, even years after youth transition to typical homes. We examined cortisol morning levels and diurnal rhythms across multiple contexts (home, school, lab) on 5 separate days in 41 post-institutionalized youth and 78 comparison youth. Employing hierarchical linear modeling, we found that when assessed in the lab, post-institutionalized (PI) youth displayed lower morning cortisol levels and flatter diurnal slopes than the control youth. Yet at home, PI youth displayed higher morning cortisol levels than the control youth. In addition to group effects, we also examined severity of early adversity and found that PI kids who had endured the most severe early adversity displayed lower home cortisol levels than controls. No significant predictors of diurnal cortisol on school days were identified. These data fit with the notion that the HPA axis is impacted by early adversity, even years after adoption, and with emerging theories that postulate that stress physiology calibrates within youth to help them adapt to their context. In the case of severe early adversity, the cost of such adaptation may not be desirable. It also highlights the important role of context when assessing HPA axis activity, particularly in post-institutionalized youth.

Early adversity, elevated stress physiology, accelerated sexual maturation, and poor health in females.

Evolutionary-minded developmentalists studying predictive-adaptive-response processes linking childhood adversity with accelerated female reproductive development and health scientists investigating the developmental origins of health and disease (DOoHaD) may be tapping the same process, whereby longer-term health costs are traded off for increased probability of reproducing before dying via a process of accelerated reproductive maturation. Using data from 73 females, we test the following propositions using path analysis: (a) greater exposure to prenatal stress predicts greater maternal depression and negative parenting in infancy, (b) which predicts elevated basal cortisol at 4.5 years, (c) which predicts accelerated adrenarcheal development, (d) which predicts more physical and mental health problems at age 18. Results prove generally consistent with these propositions, including a direct link from cortisol to mental health problems. DOoHaD investigators should consider including early sexual maturation as a core component linking early adversity and stress physiology with poor health later in life in females.

Longitudinal associations between diurnal cortisol slope and alcohol use across adolescence: a seven-year prospective study.

A large body of research has linked hypothalamic-pituitary-adrenal (HPA) axis function and alcohol consumption, including work suggesting that flatter diurnal cortisol slopes are associated with greater alcohol use. A lack of longitudinal studies and a focus on adult and alcoholic populations leaves unclear whether such associations are also present in younger, non-clinical populations and whether flatter diurnal slopes are a consequence of or preexisting risk factor for alcohol use; however, theory suggests such associations may be mutually reinforcing. In a longitudinal, community sample of 200 (55% female) adolescents, the current study demonstrates that flatter diurnal cortisol slope at age 11 predicts higher levels of alcohol use from ages 15-18, and that heavier alcohol use in turn predicts further flattening of diurnal cortisol rhythm at age 18.5. This is the first study to demonstrate a longitudinal chain of associations between diurnal cortisol slope and alcohol use. Findings support contemporary theoretical models of the neurobiological processes underlying alcohol use and can inform future research on risk factors for and consequences of underage drinking.

Associations of child insomnia, sleep movement, and their persistence with mental health symptoms in childhood and adolescence.

STUDY OBJECTIVES: To examine the patterns of insomnia and sleep-related movement from ages 4.5 to 9 years, their concurrent associations with mental health symptoms in childhood, and the longitudinal associations of sleep-problem persistence with mental health symptoms at ages 9 and 18 years. DESIGN: A 14-year prospective follow-up study. Assessments included maternal report on the Children's Sleep Habits Questionnaire at ages 4.5 and 9, and child mental health symptoms via maternal report at age 4.5, multi-informant (child, teacher, mother) report at age 9, and adolescent report at age 18. SETTING: Community. PARTICIPANTS: A total of 396 children (51% female). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Sleep problems were more common at age 4.5 than 9; symptoms of insomnia and abnormal sleep movement both had persistence rates of 9-10%. At age 4.5, insomnia was associated with hostile-aggressive and hyperactive-distractible behavior, but there were no significant associations for sleep movement. At age 9, both insomnia and sleep movement were associated with symptoms of depression, externalizing, and attention deficit hyperactivity disorder (ADHD). Insomnia persistence was associated with symptoms of depression, externalizing, and ADHD at age 9 and anxiety and externalizing at age 18; sleep- movement persistence was associated with externalizing and ADHD at age 9, and ADHD at age 18. The age 18 persistence effects for insomnia and anxiety and for sleep movement and ADHD were significant when controlling for earlier mental health. CONCLUSIONS: Childhood insomnia and sleep movement are common and associated with mental health symptoms. Their persistence from middle to late childhood predicts associations with specific types of mental health symptoms at age 18.

Adolescent adrenocortical activity and adiposity: differences by sex and exposure to early maternal depression.

Prior research has linked either basal cortisol levels or stress-induced cortisol responses to adiposity; however, it remains to be determined whether these distinct cortisol measures exert joint or independent effects. Further, it is unclear how they interact with individual and environmental characteristics to predict adiposity. The present study aims to address whether morning cortisol levels and cortisol responses to a psychosocial stressor independently and/or interactively influence body mass index (BMI) in 218 adolescents (117 female) participating in a longitudinal community study, and whether associations are moderated by sex and exposure to early maternal depression. Reports of maternal depressive symptoms were obtained in infancy and preschool. Salivary cortisol measures included a longitudinal morning cortisol measure comprising sampling points across ages 11, 13, 15, and 18 and measures of stress-induced cortisol responses assessed via the Trier Social Stress Test (TSST) at age 18. Lower morning cortisol and higher TSST cortisol reactivity independently predicted higher age 18 BMI. Morning cortisol also interacted with sex and exposure to early maternal depression to predict BMI. Specifically, girls exposed to lower levels of early maternal depression displayed a strong negative morning cortisol-BMI association, and girls exposed to higher levels of maternal depression demonstrated a weaker negative association. Among boys, those exposed to lower levels of maternal depression displayed no association, while those exposed to higher levels of maternal depression displayed a negative morning cortisol-BMI association. Results point to the independent, additive effects of morning and reactive cortisol in the prediction of BMI and suggest that exposure to early maternal depression may exert sexually dimorphic effects on normative cortisol-BMI associations.

Concurrent and longitudinal associations between diurnal cortisol and body mass index across adolescence.

PURPOSE: Childhood and adolescent obesity have reached epidemic levels; however, little is known about the psychobiological underpinnings of obesity in youth and whether these differ from the mechanisms identified in adults. The current study examines concurrent (i.e., measured at the same point in time) and longitudinal (i.e., using earlier cortisol measures to predict later body mass index [BMI]) associations between diurnal cortisol and BMI across adolescence. METHODS: Adolescent diurnal cortisol was measured over 3 days at each 11, 13, and 15 years. Hierarchical linear modeling was used to extract average measures of predicted morning, afternoon, evening levels of cortisol and the diurnal slope at each assessment. Adolescent BMI (kg/m(2)) was measured at 11, 13, 15, and 18 years. Sex, family socioeconomic status, mother's BMI, pubertal status, and adolescent mental health were examined as possible confounding variables. RESULTS: Linear regressions revealed that blunted patterns of adolescent cortisol were associated with increased measures of BMI across adolescence both concurrently and longitudinally, particularly when examining measures of cortisol in early adolescence. Multinomial logistic regressions extended the linear regression findings beyond BMI scores to encompass categories of obesity. CONCLUSIONS: The current study builds on previous research documenting diurnal cortisol-obesity findings in adults by demonstrating similar findings exist both concurrently and longitudinally in adolescents. Findings suggest the association between cortisol and BMI is developmentally influenced and that blunted diurnal cortisol patterns can be identified in overweight individuals at a younger age than previously thought.

Early risk factors for alcohol use across high school and its covariation with deviant friends.

OBJECTIVE: Past research has associated childhood characteristics and experiences with alcohol use at single time points in adolescence. Other work has focused on drinking trajectories across adolescence but with risk factors typically no earlier than middle or high school. Similarly, although the connection between underage drinking and affiliation with deviant friends is well established, early risk factors for their covariation across adolescence are uncertain. The present study examines the influence of early individual and contextual factors on (a) trajectories across high school of per-occasion alcohol use and (b) the covariation of alcohol use and deviant friends over time. METHOD: In a longitudinal community sample (n = 374; 51% female), temperamental disinhibition, authoritarian and authoritative parenting, and parental alcohol use were assessed during childhood, and adolescents reported on alcohol use and affiliation with deviant friends in the spring of Grades 9, 10, 11, and 12. RESULTS: Early parental alcohol use predicted the intercept of adolescent drinking. Subsequent patterns of adolescent alcohol use were predicted by sex and interactions of sex and childhood disinhibition with early authoritarian parenting. Additionally, childhood disinhibition interacted with parental alcohol use to moderate the covariation of drinking and deviant friends. CONCLUSIONS: These findings highlight early individual and contextual risk factors for alcohol use across high school, extending previous work and underscoring the importance of developmental approaches and longitudinal techniques for understanding patterns of growth in underage drinking.