Effects of Pollution Burden on Neural Function During Implicit Emotion Regulation and Longitudinal Changes in Depressive Symptoms in Adolescents.

Background: Exposure to environmental pollutants early in life has been associated with increased prevalence and severity of depression in adolescents; however, the neurobiological mechanisms underlying this association are not well understood. In the current longitudinal study, we investigated whether pollution burden in early adolescence (9-13 years) was associated with altered brain activation and connectivity during implicit emotion regulation and changes in depressive symptoms across adolescence. Methods: One hundred forty-five participants (n = 87 female; 9-13 years) provided residential addresses, from which we determined their relative pollution burden at the census tract level, and performed an implicit affective regulation task in the scanner. Participants also completed questionnaires assessing depressive symptoms at 3 time points, each approximately 2 years apart, from which we calculated within-person slopes of depressive symptoms. We conducted whole-brain activation and connectivity analyses to examine whether pollution burden was associated with alterations in brain function during implicit emotion regulation of positively and negatively valenced stimuli and how these effects were related to slopes of depressive symptoms across adolescence. Results: Greater pollution burden was associated with greater bilateral medial prefrontal cortex activation and stronger bilateral medial prefrontal cortex connectivity with regions within the default mode network (e.g., temporoparietal junction, posterior cingulate cortex, precuneus) during implicit regulation of negative emotions, which was associated with greater increases in depressive symptoms across adolescence in those exposed to higher pollution burden. Conclusions: Adolescents living in communities characterized by greater pollution burden showed altered default mode network functioning during implicit regulation of negative emotions that was associated with increases in depressive symptoms across adolescence.

Exposure to environmental pollution is related to increased risk for depression in youth; however, the neurobiological mechanisms underlying this association are unknown. We found that adolescents living in neighborhoods with greater census tract­level pollution burden had stronger functional connectivity between the medial prefrontal cortex and regions within the default mode network during implicit regulation of negative emotions, which in turn was associated with greater increases in depressive symptoms across adolescence in these pollution-exposed youths.

The effects of puberty and sex on adolescent white matter development: A systematic review.

Adolescence, the transition between childhood and adulthood, is characterized by rapid brain development in white matter (WM) that is attributed in part to rising levels in adrenal and gonadal hormones. The extent to which pubertal hormones and related neuroendocrine processes explain sex differences in WM during this period is unclear. In this systematic review, we sought to examine whether there are consistent associations between hormonal changes and morphological and microstructural properties of WM across species and whether these effects are sex-specific. We identified 90 (75 human, 15 non-human) studies that met inclusion criteria for our analyses. While studies in human adolescents show notable heterogeneity, results broadly demonstrate that increases in gonadal hormones across pubertal development are associated with macro- and microstructural changes in WM tracts that are consistent with the sex differences found in non-human animals, particularly in the corpus callosum. We discuss limitations of the current state of the science and recommend important future directions for investigators in the field to consider in order to advance our understanding of the neuroscience of puberty and to promote forward and backward translation across model organisms.

Stressful life events and accelerated biological aging over time in youths.

Experiencing adversity in childhood and adolescence, including stressful life events (SLEs), may accelerate the pace of development, leading to adverse mental and physical health. However, most research on adverse early experiences and biological aging (BA) in youths relies on cross-sectional designs. In 171 youths followed for approximately 2 years, we examined if SLEs over follow-up predicted rate of change in two BA metrics: epigenetic age and Tanner stage. We also investigated if rate of change in BA was associated with changes in depressive symptoms over time. Youths aged 8-16 years at baseline self-reported Tanner stage and depressive symptoms at baseline and follow-up and provided saliva samples for DNA at both assessments. Horvath epigenetic age estimates were derived from DNA methylation data measured with the Illumina EPIC array. At follow-up, contextual threat interviews were administered to youths and caregivers to assess youths' experiences of past-year SLEs. Interviews were objectively coded by an independent rating team to generate a SLE impact score, reflecting the severity of all SLEs occurring over the prior year. Rate of change in BA metrics was operationalized as change in epigenetic age or Tanner stage as a function of time between assessments. Higher objective SLE impact scores over follow-up were related to a greater rate of change in epigenetic age (ß = 0.21, p = .043). Additionally, among youths with lower-but not higher-Tanner stage at baseline, there was a positive association of SLE impact scores with rate of change in Tanner stage (Baseline Tanner Stage × SLE Impact Score interaction: ß = - 0.21, p = .011). A greater rate of change in epigenetic age was also associated with higher depressive symptom levels at follow-up, adjusting for baseline symptoms (ß = 0.15, p = .043). Associations with epigenetic age were similar, although slightly attenuated, when adjusting for epithelial (buccal) cell proportions. Whereas much research in youths has focused on severe experiences of early adversity, we demonstrate that more commonly experienced SLEs during adolescence may also contribute to accelerated BA. Further research is needed to understand the long-term consequences of changes in BA metrics for health.

Childhood trauma, earlier pubertal timing, and psychopathology in adolescence: The role of corticolimbic development.

Earlier pubertal development appears to be one pathway through which childhood trauma contributes to psychopathology in adolescence. Puberty-related changes in neural networks involved in emotion processing, namely the amygdala-medial prefrontal (mPFC) circuit, may be a potential mechanism linking trauma and adolescent psychopathology. Our participants were 227 youth between 10 and 13 years of age who completed assessments of threat and deprivation-related experiences of adversity, pubertal stage, and internalizing and externalizing symptoms. A subset (n = 149) also underwent a functional MRI scan while passively viewing fearful and calm faces. Potential mechanisms linking childhood trauma with psychopathology, encompassing earlier pubertal timing and neural response to aversive stimuli were explored. Earlier pubertal development was associated with childhood trauma as well as increased externalizing symptoms in boys only. Earlier pubertal timing in males and females was negatively associated with activation in bilateral amygdala, hippocampal, and fusiform regions when comparing fearful and calm faces. However, amygdala-mPFC connectivity showed no association with pubertal timing or psychopathology symptoms. These findings do not support accelerated amygdala-mPFC development as a mechanism linking childhood trauma and psychopathology, but instead provide support for the role of pubertal development in normative decreases in limbic activation across development.

Dimensions of Early Adversity and Sexual Behavior in a US Population-Based Adolescent Sample.

PURPOSE: Early life adversity (ELA) is associated with sexual risk, but ELA dimensions-and potential mechanisms-have been less examined. We evaluated associations between threat and deprivation-two key ELA dimensions-and sexual behaviors in adolescents. Secondary analyses investigated age at menarche as a mechanism linking ELA with sexual outcomes in girls. We predicted associations between threat and sexual behaviors, with younger age at menarche as a pathway. METHODS: Data were from the National Comorbidity Survey, Adolescent Supplement. Adolescents and caregivers reported on youths' ELA experiences, which were categorized as threat- or deprivation-related. Adolescents reported if they engaged in sex (N = 9,937) and on specific sexual risk indicators, including age at first sex, number of past-year sexual partners, and condom use consistency ("always" vs. "not always" used). Girls reported age at menarche. RESULTS: Threat (odds ratio [OR] = 1.76 [95% confidence interval [CI], 1.62-1.92]) and deprivation (OR = 1.51 [95% CI, 1.24-1.83]) were each linked with engagement in sex, ps<.05. Threat-related experiences were associated with multiple sexual risk markers, even when accounting for deprivation: earlier age at first sex (b = -0.20 [95% CI, -0.27 to 0.13]), greater number of partners (b = 0.17 [95% CI, 0.10-0.25]), and inconsistent condom use (OR = 0.72 [95% CI, 0.64-0.80]), ps <.001. Deprivation was not associated with sexual risk when adjusting for threat. We observed no significant indirect effects through age at menarche. DISCUSSION: Although threat and deprivation were related to engagement in sexual activity, threat-related experiences were uniquely associated with sexual risk. Screening for threat-related ELA may identify adolescents at-risk for poor sexual health.

Objective and subjective sleep health in adolescence: Associations with puberty and affect.

Sleep health tends to worsen during adolescence, partially due to pubertal-related changes that, in combination with social and psychological factors, can lead to long-lasting impairments in sleep health and affective functioning. Discrepant findings between subjective and objective measures of sleep in relation to affect have been reported in studies of adults; however, few investigations have assessed both subjective and objective sleep quality in a single sample, and fewer have examined this in the context of pubertal development. We aimed to (1) characterise pubertal associations with subjective sleep satisfaction, objective sleep efficiency, and objective and subjective sleep duration in adolescents; (2) examine the longitudinal association between daily affect and sleep metrics; and (3) test whether pubertal stage moderated this association. Eighty-nine participants (64% female, ages 13-20) completed an ecological momentary assessment (EMA) and actigraphy protocol. Independent of age, advanced pubertal stage was associated with lower subjective sleep satisfaction but not with objective sleep indices. Subjective sleep satisfaction was associated with within-person trajectories of negative affect, but not with positive affect. Pubertal stage and sleep satisfaction did not interact to predict within-day negative or positive affect. These findings are consistent with previous reports showing that objective and subjective sleep health are associated differently with puberty, and that subjective sleep health is associated with daily affect. Pubertal stage may be a more important indicator of subjective sleep quality in adolescence than is chronological age, most likely due to hormonal changes and psychological adjustment to the physical changes associated with the pubertal transition.

Early life stress, systemic inflammation, and neural correlates of implicit emotion regulation in adolescents.

Exposure to early life stress (ELS) increases the risk for developing psychopathology; however, the mechanisms underlying this association are not clear. In this study we examined systemic inflammation as a pathway that may link exposure to stress to altered neural correlates of implicit emotion regulation in adolescents with varying levels of exposure to ELS (n = 83; 52 females, 31 males; 15.63 ± 1.10 years). We measured ventrolateral prefrontal cortex (vlPFC) activation and functional connectivity (FC) between the bilateral amygdala and the vlPFC as adolescents completed an affect labeling task in the scanner and assessed concentrations of C-reactive protein (CRP) using a dried blood spot protocol. We found that CRP levels were negatively associated with vlPFC activation during implicit regulation of negatively-valenced stimuli, and that cumulative severity of ELS exposure moderated this neuroimmune association. Severity of ELS also significantly moderated the association between CRP levels and FC between the bilateral amygdala and l-vlPFC during implicit emotion regulation: in adolescents who had been exposed to more severe ELS, higher CRP was associated with more negative frontoamygdala FC during implicit regulation of negatively-valenced stimuli. Thus, ELS may disrupt the normative association between the immune system and the neural processes that underlie socioemotional functioning potentially increasing adolescents' risk for maladaptive outcomes.

Accelerated pubertal development as a mechanism linking trauma exposure with depression and anxiety in adolescence.

Exposure to early-life adversity (ELA) is associated with elevated risk for depression and anxiety disorders in adolescence. Identifying mechanisms through which ELA contributes to the emergence of depression and anxiety is necessary to design preventive interventions. One potential mechanism linking exposure to ELA with psychopathology is accelerated pubertal development. Exposure to trauma-specifically interpersonal violence-is associated with earlier pubertal timing, which in turn predicts adolescent-onset depression and anxiety disorders. We review the recent literature on adversity and accelerated pubertal development, exploring specific associations between trauma and accelerated pubertal development as a mechanism linking adversity with depression and anxiety disorders in adolescence. Finally, we suggest future directions for research exploring mechanisms linking ELA with accelerated pubertal development as well as pubertal timing and psychopathology in adolescence.

Exposure to Violence as an Environmental Pathway Linking Low Socioeconomic Status with Altered Neural Processing of Threat and Adolescent Psychopathology.

Low childhood socioeconomic status (SES) is associated with increased risk for psychopathology, in part because of heightened exposure to environmental adversity. Adverse experiences can be characterized along dimensions, including threat and deprivation, that contribute to psychopathology via distinct mechanisms. The current study investigated a neural mechanism through which threat and deprivation may contribute to socioeconomic disparities in psychopathology. Participants were 177 youths (83 girls) aged 10-13 years recruited from a cohort followed since the age of 3 years. SES was assessed using the income-to-needs ratio at the age of 3 years. At the age of 10-13 years, retrospective and current exposure to adverse experiences and symptoms of psychopathology were assessed. At this same time point, participants also completed a face processing task (passive viewing of fearful and neutral faces) during an fMRI scan. Lower childhood SES was associated with greater exposure to threat and deprivation experiences. Both threat and deprivation were associated with higher depression symptoms, whereas threat experiences were uniquely linked to posttraumatic stress disorder symptoms. Greater exposure to threat, but not deprivation, was associated with higher activation in dorsomedial pFC to fearful compared with neutral faces. The dorsomedial pFC is a hub of the default mode network thought to be involved in internally directed attention and cognition. Experiences of threat, but not deprivation, are associated with greater engagement of this region in response to threat cues. Threat-related adversity contributes to socioeconomic disparities in adolescent psychopathology through distinct mechanisms from deprivation.

White-matter tract connecting anterior insula to nucleus accumbens predicts greater future motivation in adolescents.

The motivation to approach or avoid incentives can change during adolescence. Advances in neuroimaging allow researchers to characterize specific brain circuits that underlie these developmental changes. Whereas activity in the nucleus accumbens (NAcc) can predict approach toward incentive gain, activity in anterior insula (AIns) is associated with avoidance of incentive loss. Recent research characterized the structural white-matter tract connecting the two brain regions, but the tract has neither been characterized in adolescence nor linked to functional activity during incentive anticipation. In this study, we collected diffusion MRI and characterized the tract connecting the AIns to the NAcc for the first time in early adolescents. We then measured NAcc functional activity during a monetary incentive delay task and found that structural coherence of the AIns-NAcc tract is correlated with decreased functional activity at the NAcc terminal of the tract during anticipation of no incentives. In adolescents who completed an assessment 2 years later, we found that AIns-NAcc tract coherence could predict greater future self-reported motivation, and that NAcc functional activity could statistically mediate this association. Together, the findings establish links from brain structure to function to future motivation and provide targets to study the reciprocal development of brain structure and function.

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

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

Biological aging in childhood and adolescence following experiences of threat and deprivation: A systematic review and meta-analysis.

Life history theory argues that exposure to early life adversity (ELA) accelerates development, although existing evidence for this varies. We present a meta-analysis and systematic review testing the hypothesis that ELA involving threat (e.g., violence exposure) will be associated with accelerated biological aging across multiple metrics, whereas exposure to deprivation (e.g., neglect, institutional rearing) and low-socioeconomic status (SES) will not. We meta-analyze 54 studies (n = 116,010) examining associations of ELA with pubertal timing and cellular aging (telomere length and DNA methylation age), systematically review 25 studies (n = 3,253) examining ELA and neural markers of accelerated development (cortical thickness and amygdala-prefrontal cortex functional connectivity) and evaluate whether associations of ELA with biological aging vary according to the nature of adversity experienced. ELA overall was associated with accelerated pubertal timing (d = -0.10) and cellular aging (d = -0.21), but these associations varied by adversity type. Moderator analysis revealed that ELA characterized by threat was associated with accelerated pubertal development (d = -0.26) and accelerated cellular aging (d = -0.43), but deprivation and SES were unrelated to accelerated development. Systematic review revealed associations between ELA and accelerated cortical thinning, with threat-related ELA consistently associated with thinning in ventromedial prefrontal cortex, and deprivation and SES associated with thinning in frontoparietal, default, and visual networks. There was no consistent association of ELA with amygdala-PFC connectivity. These findings suggest specificity in the types of early environmental experiences associated with accelerated biological aging and highlight the importance of evaluating how accelerated aging contributes to health disparities and whether this process can be mitigated through early intervention. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Sex differences in the effects of gonadal hormones on white matter microstructure development in adolescence.

Adolescence is characterized by rapid brain development in white matter (WM) that is attributed in part to surges in gonadal hormones. To date, however, there have been few longitudinal investigations relating changes in gonadal hormones and WM development in adolescents. We acquired diffusion-weighted MRI to estimate mean fractional anisotropy (FA) from 10 WM tracts and salivary testosterone from 51 females and 29 males (ages 9-14 years) who were matched on pubertal stage and followed, on average, for 2 years. We tested whether interactions between sex and changes in testosterone levels significantly explained changes in FA. We found positive associations between changes in testosterone and changes in FA within the corpus callosum, cingulum cingulate, and corticospinal tract in females (all ps<0.05, corrected) and non-significant associations in males. We also collected salivary estradiol from females and found that increases in estradiol were associated with increases in FA in the left uncinate fasciculus (p = 0.04, uncorrected); however, this effect was no longer significant after accounting for changes in testosterone. Our findings indicate there are sex differences in how changes in testosterone relate to changes in WM microstructure of tracts that support impulse control and emotion regulation across the pubertal transition.

Mechanisms linking childhood trauma exposure and psychopathology: a transdiagnostic model of risk and resilience.

BACKGROUND: Transdiagnostic processes confer risk for multiple types of psychopathology and explain the co-occurrence of different disorders. For this reason, transdiagnostic processes provide ideal targets for early intervention and treatment. Childhood trauma exposure is associated with elevated risk for virtually all commonly occurring forms of psychopathology. We articulate a transdiagnostic model of the developmental mechanisms that explain the strong links between childhood trauma and psychopathology as well as protective factors that promote resilience against multiple forms of psychopathology. MAIN BODY: We present a model of transdiagnostic mechanisms spanning three broad domains: social information processing, emotional processing, and accelerated biological aging. Changes in social information processing that prioritize threat-related information-such as heightened perceptual sensitivity to threat, misclassification of negative and neutral emotions as anger, and attention biases towards threat-related cues-have been consistently observed in children who have experienced trauma. Patterns of emotional processing common in children exposed to trauma include elevated emotional reactivity to threat-related stimuli, low emotional awareness, and difficulties with emotional learning and emotion regulation. More recently, a pattern of accelerated aging across multiple biological metrics, including pubertal development and cellular aging, has been found in trauma-exposed children. Although these changes in social information processing, emotional responding, and the pace of biological aging reflect developmental adaptations that may promote safety and provide other benefits for children raised in dangerous environments, they have been consistently associated with the emergence of multiple forms of internalizing and externalizing psychopathology and explain the link between childhood trauma exposure and transdiagnostic psychopathology. Children with higher levels of social support, particularly from caregivers, are less likely to develop psychopathology following trauma exposure. Caregiver buffering of threat-related processing may be one mechanism explaining this protective effect. CONCLUSION: Childhood trauma exposure is a powerful transdiagnostic risk factor associated with elevated risk for multiple forms of psychopathology across development. Changes in threat-related social and emotional processing and accelerated biological aging serve as transdiagnostic mechanisms linking childhood trauma with psychopathology. These transdiagnostic mechanisms represent critical targets for early interventions aimed at preventing the emergence of psychopathology in children who have experienced trauma.

Associations of waking cortisol with DHEA and testosterone across the pubertal transition: Effects of threat-related early life stress.

Atypical regulation of the hypothalamic-pituitary-adrenal (HPA) axis is a putative mechanism underlying the association between exposure to early life stress (ELS) and the subsequent development of mental and physical health difficulties. Recent research indicates that puberty is a period of HPA-axis plasticity during which the effects of exposure to ELS on cortisol regulation may change. In particular, increases in the sex hormones that drive pubertal maturation, including dehydroepiandrosterone (DHEA) and testosterone, may be implicated in pubertal recalibration of cortisol regulation. In the current study, we examined the associations among levels of objectively-rated threat-related ELS and salivary waking cortisol, DHEA, and testosterone in a sample of 178 adolescents (55 % female) who were in early puberty at baseline (Tanner stages 1-3; mean Tanner stage[SD] = 1.93[0.64]; mean age[SD] = 11.42[1.04]) and were followed up approximately two years later (mean Tanner stage[SD] = 3.46[0.86]; mean age[SD] = 13.38[1.06]). Using multi-level modeling, we disaggregated the effects of between-individual levels and within-individual increases in pubertal stage and sex hormones on change in cortisol. Controlling for between-individual differences in average pubertal stage, the association between levels of cortisol and DHEA was more strongly positive among adolescents who evidenced greater within-individual increases in pubertal stage across time. Both higher average levels and greater within-individual increases in DHEA and testosterone were associated with increases in cortisol across time, indicating positive coupling of developmental changes in these hormones; however, coupling was attenuated in adolescents who were exposed to more severe threat-related ELS prior to puberty. These findings advance our understanding of the development of the HPA-axis and its association with childhood environmental risk during puberty.

Early Life Stress, Frontoamygdala Connectivity, and Biological Aging in Adolescence: A Longitudinal Investigation.

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.

Altered Neural Processing of Threat-Related Information in Children and Adolescents Exposed to Violence: A Transdiagnostic Mechanism Contributing to the Emergence of Psychopathology.

OBJECTIVE: Exposure to violence in childhood is associated with increased risk for multiple forms of internalizing and externalizing psychopathology. We evaluated how exposure to violence in early life influences neural responses to neutral and threat-related stimuli in childhood and adolescence, developmental variation in these associations, and whether these neural response patterns convey transdiagnostic risk for psychopathology over time. METHOD: Participants were 149 youths (75 female and 74 male), aged 8 to 17 years (mean = 12.8, SD = 2.63), who had experienced physical abuse, sexual abuse, or domestic violence (n = 76) or had never experienced violence (n = 73). Participants underwent functional magnetic resonance imaging scanning while passively viewing fearful, neutral, and scrambled faces presented rapidly in a block design without specific attentional demands. Internalizing and externalizing psychopathology were assessed concurrently with the scan and 2 years later and were used to compute a transdiagnostic general psychopathology factor (p factor). RESULTS: Exposure to violence was associated with reduced activation in the dorsal anterior cingulate cortex (dACC) and frontal pole (1,985 voxels, peak x, y, z = 6, 4, 40) when viewing fearful (versus scrambled) faces, and reduced activation in dorsomedial prefrontal cortex and superior frontal gyrus (1,970 voxels, peak x, y, z = 16, 64, 10) when viewing neutral faces, but not amygdala activation or connectivity. Lower dACC response to fearful faces predicted increase in the p factor 2 years later (B = -0.186, p = .031) and mediated the association of violence exposure with longitudinal increases in the p factor. CONCLUSION: Reduced recruitment of the dACC-a region involved in salience processing, conflict monitoring, and cognitive control-in response to threat-related cues may convey increased transdiagnostic psychopathology risk in youths exposed to violence.

Earlier age at menarche as a transdiagnostic mechanism linking childhood trauma with multiple forms of psychopathology in adolescent girls.

BACKGROUND: Although early life adversity (ELA) increases risk for psychopathology, mechanisms linking ELA with the onset of psychopathology remain poorly understood. Conceptual models have argued that ELA accelerates development. It is unknown whether all forms of ELA are associated with accelerated development or whether early maturation is a potential mechanism linking ELA with psychopathology. We examine whether two distinct dimensions of ELA - threat and deprivation - have differential associations with pubertal timing in girls, and evaluate whether accelerated pubertal timing is a mechanism linking ELA with the onset of adolescent psychopathology. METHODS: Data were drawn from a large, nationally representative sample of 4937 adolescent girls. Multiple forms of ELA characterized by threat and deprivation were assessed along with age at menarche (AAM) and the onset of DSM-IV fear, distress, externalizing, and eating disorders. RESULTS: Greater exposure to threat was associated with earlier AAM (B = -0.1, p = 0.001). Each 1-year increase in AAM was associated with reduced odds of fear, distress, and externalizing disorders post-menarche (ORs = 0.74-0.85). Earlier AAM significantly mediated the association between exposure to threat and post-menarche onset of distress (proportion mediated = 6.2%), fear (proportion mediated = 16.3%), and externalizing disorders (proportion mediated = 2.9%). CONCLUSIONS: Accelerated pubertal development in girls may be one transdiagnostic pathway through which threat-related experiences confer risk for the adolescent onset of mental disorders. Early pubertal maturation is a marker that could be used in both medical and mental health settings to identify trauma-exposed youth that are at risk for developing a mental disorder during adolescence in order to better target early interventions.

Early life stress, cortisol, frontolimbic connectivity, and depressive symptoms during puberty.

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.

Reward-circuit biomarkers of risk and resilience in adolescent depression.

BACKGROUND: Dysfunctional reward processing is a core feature of major depressive disorder. While there is growing knowledge of reward processing in adolescent depression, researchers have ignored neural mechanisms of resilience to depression. Here, we examine neural correlates of reward processing that characterize resilience and risk in adolescents at risk for depression, facilitating the development of effective intervention approaches that strengthen resilience to psychopathology in at-risk youth. METHODS: 50 adolescent females were followed through age 18: 32 at-risk adolescents who either did (remitted-depressed; n = 15) or did not (resilient; n = 17) experience a depressive episode, and 18 low-risk healthy controls. Participants completed clinical assessments at 18-month intervals and an fMRI reward-processing task in late adolescence. We conducted predictive modeling with a priori reward regions of interest (ROIs). RESULTS: At-risk resilient and remitted-depressed adolescents exhibited less striatal activation than did controls during anticipation of reward. Resilient adolescents exhibited greater activation than did remitted-depressed adolescents in the middle frontal gyrus during reward anticipation, and less activation in the superior frontal gyrus and cuneus during processing of reward outcome. Using predictive modeling, ventral anterior cingulate cortex and putamen activation during reward processing distinguished resilient from remitted-depressed adolescents with 83% accuracy. LIMITATIONS: The relatively small sample size of only females and the fact that fMRI data were obtained at one time point in late adolescence are limitations. CONCLUSIONS: Distinct patterns of neural activation in reward circuitry appear to be markers of risk and resilience that may be targets for prevention and treatment approaches aimed at strengthening adaptive reward processing in at-risk adolescents.