Relationship between COVID-related stressors and internalizing symptoms: Gendered neuroendocrine risk profiles.

The COVID-19 pandemic generated significant life stress and increases in internalizing disorders. Moreover, COVID-related stressors disproportionately impacted women, consistent with outcomes showing a gender gap in stress-related disorders. Gender-related stress vulnerability emerges in adolescence alongside gender-specific changes in neuroendocrine signaling. Most research on the neuroendocrinology of stress-related disorders has focused on differences in the hypothalamic-pituitary-adrenal (HPA) axis effector hormone cortisol. More recent studies, however, emphasize dehydroepiandrosterone (DHEA), a neuroprotective and neuroactive hormone released concurrently with cortisol that balances its biobehavioral actions during stress. Notably, women show lower cortisol responses and higher DHEA responses to stress. However, lower cortisol and higher DHEA are associated with internalizing disorders in women, while those associations are opposite in men. Thus, gender-specific factors perhaps result in a neuroendocrine profile that places women at greater risk for stress-related disorders. The current study prospectively examined socially evaluated cold-pressor task (SECPT) induced neuroendocrine responses at age 15 and internalizing symptoms during the COVID-19 pandemic at age 21 in a cohort of 175 primarily Black low-socioeconomic status participants, while controlling for internalizing symptoms at age 15. The association between COVID-related stress and internalizing symptoms was not stronger in women. Lower DHEA-cortisol ratios were associated with a weaker relationship between COVID-related stress and internalizing symptoms in women, while higher ratios were associated with a weaker relationship in men. These findings suggest gender differences in the relationship between DHEA and cortisol and internalizing outcomes during a stressful period, and support differential neuroendocrine protective and risk pathways for young men and women.

Parent Mental Health Before and During the COVID-19 Pandemic.

Although extant cross-sectional data suggest that parents have experienced numerous challenges (e.g., homeschooling, caregiver burden) and mental health consequences during the COVID-19 pandemic, longitudinal data are needed to confirm mental health changes relative to pre-pandemic levels and identify which specific pandemic-related changes most highly predict mental health during the pandemic. In two longitudinal subsamples (N = 299 and N = 175), we assessed change in anxiety, depression, and stress before and during the pandemic and whether the accumulation of pandemic-related changes predicted observed mental health changes. On average, parents reported increased depression and anxiety, but no significant changes in reported stress. Moreover, increased interpersonal conflict, difficulty managing work and caregiving responsibilities, and increased economic challenges were the types of pandemic-related changes that most strongly predicted worse mental health, highlighting that juggling caregiving responsibilities and economic concerns, along with the pandemic's impact on interpersonal family relationships are key predictors of worsening parental mental illness symptoms.

Antisocial behavior is associated with reduced frontoparietal activity to loss in a population-based sample of adolescents.

BACKGROUND: Adolescent antisocial behavior (AB) is a public health concern due to the high financial and social costs of AB on victims and perpetrators. Neural systems involved in reward and loss processing are thought to contribute to AB. However, investigations into these processes are limited: few have considered anticipatory and consummatory components of reward, response to loss, nor whether associations with AB may vary by level of callous-unemotional (CU) traits. METHODS: A population-based community sample of 128 predominantly low-income youth (mean age = 15.9 years; 42% male) completed a monetary incentive delay task during fMRI. A multi-informant, multi-method latent variable approach was used to test associations between AB and neural response to reward and loss anticipation and outcome and whether CU traits moderated these associations. RESULTS: AB was not associated with neural response to reward but was associated with reduced frontoparietal activity during loss outcomes. This association was moderated by CU traits such that individuals with higher levels of AB and CU traits had the largest reductions in frontoparietal activity. Co-occurring AB and CU traits were also associated with increased precuneus response during loss anticipation. CONCLUSIONS: Findings indicate that AB is associated with reduced activity in brain regions involved in cognitive control, attention, and behavior modification during negative outcomes. Moreover, these reductions are most pronounced in youth with co-occurring CU traits. These findings have implications for understanding why adolescents involved in AB continue these behaviors despite severe negative consequences (e.g. incarceration).

Adolescent functional network connectivity prospectively predicts adult anxiety symptoms related to perceived COVID-19 economic adversity.

BACKGROUND: Stressful events, such as the COVID-19 pandemic, are major contributors to anxiety and depression, but only a subset of individuals develop psychopathology. In a population-based sample (N = 174) with a high representation of marginalized individuals, this study examined adolescent functional network connectivity as a marker of susceptibility to anxiety and depression in the context of adverse experiences. METHODS: Data-driven network-based subgroups were identified using an unsupervised community detection algorithm within functional neural connectivity. Neuroimaging data collected during emotion processing (age 15) were extracted from a priori regions of interest linked to anxiety and depression. Symptoms were self-reported at ages 15, 17, and 21 (during COVID-19). During COVID-19, participants reported on pandemic-related economic adversity. Differences across subgroup networks were first examined, then subgroup membership and subgroup-adversity interaction were tested to predict change in symptoms over time. RESULTS: Two subgroups were identified: Subgroup A, characterized by relatively greater neural network variation (i.e., heterogeneity) and density with more connections involving the amygdala, subgenual cingulate, and ventral striatum; and the more homogenous Subgroup B, with more connections involving the insula and dorsal anterior cingulate. Accounting for initial symptoms, subgroup A individuals had greater increases in symptoms across time (ß = .138, p = .042), and this result remained after adjusting for additional covariates (ß = .194, p = .023). Furthermore, there was a subgroup-adversity interaction: compared with Subgroup B, Subgroup A reported greater anxiety during the pandemic in response to reported economic adversity (ß = .307, p = .006), and this remained after accounting for initial symptoms and many covariates (ß = .237, p = .021). CONCLUSIONS: A subgrouping algorithm identified young adults who were susceptible to adversity using their personalized functional network profiles derived from a priori brain regions. These results highlight potential prospective neural signatures involving heterogeneous emotion networks that predict individuals at the greatest risk for anxiety when experiencing adverse events.

Amygdala reactivity during socioemotional processing and cortisol reactivity to a psychosocial stressor.

Threat-related amygdala reactivity and the activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis have been linked to negative psychiatric outcomes. The amygdala and HPA axis have bidirectional connections, suggesting that functional variation in one system may influence the other. However, research on the functional associations between these systems has demonstrated mixed findings, potentially due to small sample sizes and cortisol sampling and data analytic procedures that investigate only pre-post differences in cortisol rather than the specific phases of the cortisol stress response. Further, previous research has primarily utilized samples of adults of mostly European descent, limiting generalizability to those of other ethnoracial identities and ages. Therefore, studies addressing these limitations are needed in order to investigate the functional relations between amygdala reactivity to threat and HPA axis stress responsivity. Using a sample of 159 adolescents from a diverse cohort (75% African American, ages 15-17 years), the present study evaluated associations between amygdala reactivity during socioemotional processing using fMRI and HPA axis reactivity to a socially-evaluative cold pressor task. Greater amygdala activation to fearful and neutral faces was associated with greater cortisol peak values and steeper activation slope. As cortisol peak values and cortisol activation slope capture the intensity of the cortisol stress response, these data suggest that greater activation of the amygdala in response to social distress and ambiguity among adolescents may be related to hyper-reactivity of the HPA axis.

Differential associations of parental harshness and parental disengagement with overall cortisol output at 15 years: Implications for adolescent mental health.

Psychosocial stress in childhood and adolescence is linked to stress system dysregulation, although few studies have examined the relative impacts of parental harshness and parental disengagement. This study prospectively tested whether parental harshness and disengagement show differential associations with overall cortisol output in adolescence. Associations between overall cortisol output and adolescent mental health problems were tested concurrently. Adolescents from the Fragile Families and Child Wellbeing Study (FFCWS) provided hair samples for cortisol assay at 15 years (N = 171). Caregivers reported on parental harshness and disengagement experiences at 1, 3, 5, 9, and 15 years, and adolescents reported at 15 years. Both parent and adolescent reported depressive and anxiety symptoms and antisocial behaviors at 15. Greater parental harshness from 1-15 years, and harshness reported at 15 years in particular, was associated with higher overall cortisol output at 15. Greater parental disengagement from 1-15 years, and disengagement at 1 year specifically, was associated with lower cortisol output. There were no significant associations between cortisol output and depressive symptoms, anxiety symptoms, or antisocial behaviors. These results suggest that the unique variances of parental harshness and disengagement may have opposing associations with cortisol output at 15 years, with unclear implications for adolescent mental health.

Differential Developmental Associations of Material Hardship Exposure and Adolescent Amygdala-Prefrontal Cortex White Matter Connectivity.

Accumulating literature has linked poverty to brain structure and function, particularly in affective neural regions; however, few studies have examined associations with structural connections or the importance of developmental timing of exposure. Moreover, prior neuroimaging studies have not used a proximal measure of poverty (i.e., material hardship, which assesses food, housing, and medical insecurity) to capture the lived experience of growing up in harsh economic conditions. The present investigation addressed these gaps collectively by examining the associations between material hardship (ages 1, 3, 5, 9, and 15 years) and white matter connectivity of frontolimbic structures (age 15 years) in a low-income sample. We applied probabilistic tractography to diffusion imaging data collected from 194 adolescents. Results showed that material hardship related to amygdala-prefrontal, but not hippocampus-prefrontal or hippocampus-amygdala, white matter connectivity. Specifically, hardship during middle childhood (ages 5 and 9 years) was associated with greater connectivity between the amygdala and dorsomedial pFC, whereas hardship during adolescence (age 15 years) was related to reduced amygdala-orbitofrontal (OFC) and greater amygdala-subgenual ACC connectivity. Growth curve analyses showed that greater increases of hardship across time were associated with both greater (amygdala-subgenual ACC) and reduced (amygdala-OFC) white matter connectivity. Furthermore, these effects remained above and beyond other types of adversity, and greater hardship and decreased amygdala-OFC connectivity were related to increased anxiety and depressive symptoms. Results demonstrate that the associations between material hardship and white matter connections differ across key prefrontal regions and developmental periods, providing support for potential windows of plasticity for structural circuits that support emotion processing.

Early life stress sensitizes youth to the influence of stress-induced cortisol on memory for affective words.

Early life stress (ELS) is a well-established risk factor for psychopathology across the lifespan. Cognitive vulnerability to stress-induced cortisol may explain risk and resilience. The current study aimed to elucidate a psychobiological pathway linking stress to altered memory for affective words among youth with and without exposure to ELS. One hundred and fifteen youth (ages 9-16, 47% female) were randomized either to a psychosocial stressor or a control condition. Immediately following the stress or control condition, participants completed a memory task for affective words. Change in salivary cortisol from immediately before to 25 min after stress onset were used to predict memory for affective words. Exposure to the acute laboratory stressor led to activation of the HPA axis. Greater cortisol reactivity was associated with less accurate recognition of negative valence words. Among youth exposed to ELS, greater cortisol reactivity to acute stress was associated with poorer recognition of dysphoric and neutral words. Acute increases in cortisol may interfere with negatively-valenced information processing that has implications for memory. Youth exposed to high ELS may be particularly vulnerable to the effects of cortisol, which may explain one pathway through which stress leads to psychopathology among at-risk youth.

Neural mechanisms of reward and loss processing in a low-income sample of at-risk adolescents.

Adolescence is a time of engagement in risky, reward-driven behaviors, with concurrent developmental changes within reward-related neural systems. As previous research has recruited mostly higher socioeconomic, European and European American participants, therefore limiting generalizability to the US population, especially for populations of color or low-income populations. The current study provided one of the first opportunities to examine the neural correlates of reward and loss functioning in a population-based sample of adolescents at increased risk for poverty-related adversities. The study investigated neural reward and loss processing and whether age, pubertal status and the social constructs of gender and race predicted individual differences in reward- and loss-related brain function. One hundred and twenty-eight primarily low-income adolescents (mean age: 15.9 years, 75% African American) from urban environments completed a modified monetary incentive delay task during functional magnetic resonance imaging (fMRI). Consistent with the previous research, reward and loss anticipation recruited similar motivational circuitry including striatal, insular, thalamic and supplementary motor areas. Race and gender were not associated with reward- or loss-related neural reactivity. Age and pubertal development were associated with differences in neural reactivity to reward and loss, suggesting that older and more mature adolescents had increased activity in sensory and motivational circuits, but decreased activity in regions responsible for error detection and behavior modification.

Childhood violence exposure and social deprivation are linked to adolescent threat and reward neural function.

BACKGROUND: Childhood adversity is, unfortunately, highly prevalent and strongly associated with later psychopathology. Recent theories posit that two dimensions of early adversity, threat and deprivation, have distinct effects on brain development. The current study evaluated whether violence exposure (threat) and social deprivation (deprivation) were associated with adolescent amygdala and ventral striatum activation, respectively, in a prospective, well-sampled, longitudinal cohort using a pre-registered, open science approach. METHODS: One hundred and sixty-seven adolescents from the Fragile Families and Child Wellbeing Study completed functional magnetic resonance imaging (fMRI) scanning. Prospective longitudinal data from ages 3, 5 and 9 years were used to create indices of childhood violence exposure and social deprivation. We evaluated whether these dimensions were associated with adolescent brain function in response to threatening and rewarding faces. RESULTS: Childhood violence exposure was associated with decreased amygdala habituation (i.e. more sustained activation) and activation to angry faces in adolescence, whereas childhood social deprivation was associated with decreased ventral striatum activation to happy faces in adolescence. These associations held when adjusting for the other dimension of adversity (e.g., adjusting for social deprivation when examining associations with violence exposure), the interaction of the two dimensions of adversity, gender, internalizing psychopathology, and current life stress. CONCLUSIONS: Consistent with recent theories, different forms of early adversity were associated with region-specific differences in brain activation.

WITHDRAWN:Childhood violence exposure and social deprivation predict adolescent amygdala-orbitofrontal cortex white matter connectivity.

This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been withdrawn at the request of the editor and publisher. The publisher regrets that an error occurred which led to the premature publication of this paper. This error bears no reflection on the article or its authors. The publisher apologizes to the authors and the readers for this unfortunate error.

Childhood violence exposure and social deprivation predict adolescent amygdala-orbitofrontal cortex white matter connectivity.

Childhood adversity is heterogeneous with potentially distinct dimensions of violence exposure and social deprivation. These dimensions may differentially shape emotion-based neural circuitry, such as amygdala-PFC white matter connectivity. Amygdala-orbitofrontal cortex (OFC) white matter connectivity has been linked to regulation of the amygdala's response to emotional stimuli. Using a preregistered analysis plan, we prospectively examined the effects of childhood exposure to two dimensions of adversity, violence exposure and social deprivation, on the adolescent amygdala-PFC white matter connectivity. We also reproduced the negative correlation between amygdala-PFC white matter connectivity and amygdala activation to threat faces. 183 15-17-year-olds were recruited from the Fragile Families and Child Wellbeing Study - a longitudinal, birth cohort, sample of predominantly low-income youth. Probabilistic tractography revealed that childhood violence exposure and social deprivation interacted to predict the probability of adolescent right hemisphere amygdala-OFC white matter connectivity. High violence exposure with high social deprivation related to less amygdala-OFC white matter connectivity. Violence exposure was not associated with white matter connectivity when social deprivation was at mean or low levels (i.e., relatively socially supportive contexts). Therefore, social deprivation may exacerbate the effects of childhood violence exposure on the development of white matter connections involved in emotion processing and regulation. Conversely, social support may buffer against them.

The roles of comorbidity and trauma exposure and its timing in shaping HPA axis patterns in depression.

BACKGROUND: Much work has documented hypothalamic pituitary adrenal (HPA) axis abnormalities in major depressive disorder (MDD), but inconsistencies leave this system's role in the illness unclear. Comparisons across studies are complicated by variation in co-morbidity (Posttraumatic Stress Disorder-PTSD, anxiety disorders), exposure to trauma, and timing of trauma (child vs. adult). Here, we examined the impact of these factors on HPA axis profiles in depression. METHODS: We recruited 5 groups of participants: MDD (n = 14), comorbid MDD + PTSD following adulthood trauma (MDD + PTSD-Adult; n = 12), comorbid MDD + PTSD following childhood trauma (MDD + PTSD-Child; n = 18), comorbid MDD + social anxiety disorder (MDD + SAD; n = 12), and non-depressed control participants who were sex and age matched to patients (combined total n = 36). HPA axis function was assessed using three challenges: stress reactivity via the Trier Social Stress Test (TSST), feedback sensitivity via a dexamethasone suppression test (DST), and central drive via a metyrapone challenge (MET). We compared hormonal responses between patient groups and their respective non-depressed controls. RESULTS: MDD + PTSD-Child showed low cortisol levels at baseline, and reduced adrenocorticotropic hormone (ACTH) levels at baseline and throughout the TSST. MDD-only, MDD + PTSD-Adult, and MDD + SAD did not differ from non-depressed controls in HPA axis responses to the TSST. Controlling for childhood trauma severity, the reduced baseline levels in MDD + PTSD-Child were no longer significant and significantly reduced baseline cortisol levels emerged for MDD + PTSD-Adult. No diagnostic group effects were detected with DST and MET. Childhood maltreatment subtypes were associated with unique HPA axis responses to TSST and MET. CONCLUSION: Comorbidity and trauma exposure, as well as their timing and type, contribute to inconsistencies in the depression literature and must be included in efforts to clarify the role of the HPA axis in MDD.

Violence exposure and social deprivation is associated with cortisol reactivity in urban adolescents.

The present study tested how two different dimensions of childhood adversity, violence exposure and social deprivation, were associated with the cortisol response to the Socially Evaluated Cold-Pressor task in a sample of 222 adolescents (n = 117 girls, n = 167 African American). Participants were part of the Fragile Families and Child Wellbeing Study, a probability sample of births in large US cities (>200,000) between 1998 and 2000. Our subsample includes births in three cities: Detroit, Toledo, and Chicago. The study design called for an oversampling of births to unmarried parents (3:1) which led to a large number of minority and economically disadvantaged adolescents. When children were ages 3, 5, and 9, mothers reported on exposures to violence and social deprivation that occurred in the past year. Exposures from the three waves were averaged to reflect violence exposure and social deprivation during childhood. Greater levels of violence exposure from ages 3 to 9 were associated with a blunted cortisol response to stress at age 15, even after controlling for social deprivation and other factors known to influence cortisol reactivity. Social deprivation from ages 3 to 9 was not associated with the cortisol response to stress; though in an exploratory analysis, social deprivation moderated the association between violence exposure and cortisol peak activation. In line with the Dimensional Model of Adversity and Psychopathology, these findings suggest that experiences of violence, but not social deprivation, during childhood may contribute to cortisol blunting that has been previously reported in samples with high levels of social deprivation. Findings from the present longitudinal study on a relatively large sample of under-represented minority youth provide insight into the ways two different dimensions of childhood adversity impact the cortisol response to stress.

Acute sleep deprivation and the selective consolidation of emotional memories.

Research suggests that sleep preferentially consolidates the negative aspects of memories at the expense of the neutral aspects. However, the mechanisms by which sleep facilitates this emotional memory trade-off remain unknown. Although active processes associated with sleep-dependent memory consolidation have been proposed to underlie this effect, this trade-off may also be modulated by non-sleep-related processes, such as the circadian factors, stress-related factors, and/or mood congruent context effects involved in sleep deprivation. We sought to examine the potential role of these factors by randomizing 39 young adults into either a total sleep deprivation condition (26 consecutive hours awake) or a sleep condition (8 h sleep opportunity). Replicating the emotional memory trade-off effect, negative objects were better remembered than neutral objects or background images. However, in spite of generally worse memory performance (for neutral and background information), sleep-deprived participants showed similar recognition rates for negative emotional memories relative to participants who were given a full night of sleep.

Giving Voice to Vulnerable Children: Machine Learning Analysis of Speech Detects Anxiety and Depression in Early Childhood.

Childhood anxiety and depression often go undiagnosed. If left untreated these conditions, collectively known as internalizing disorders, are associated with long-term negative outcomes including substance abuse and increased risk for suicide. This paper presents a new approach for identifying young children with internalizing disorders using a 3-min speech task. We show that machine learning analysis of audio data from the task can be used to identify children with an internalizing disorder with 80% accuracy (54% sensitivity, 93% specificity). The speech features most discriminative of internalizing disorder are analyzed in detail, showing that affected children exhibit especially low-pitch voices, with repeatable speech inflections and content, and high-pitched response to surprising stimuli relative to controls. This new tool is shown to outperform clinical thresholds on parent-reported child symptoms, which identify children with an internalizing disorder with lower accuracy (67-77% versus 80%), and similar specificity (85-100% versus 93%), and sensitivity (0-58% versus 54%) in this sample. These results point toward the future use of this approach for screening children for internalizing disorders so that interventions can be deployed when they have the highest chance for long-term success.

Rapid detection of internalizing diagnosis in young children enabled by wearable sensors and machine learning.

There is a critical need for fast, inexpensive, objective, and accurate screening tools for childhood psychopathology. Perhaps most compelling is in the case of internalizing disorders, like anxiety and depression, where unobservable symptoms cause children to go unassessed-suffering in silence because they never exhibiting the disruptive behaviors that would lead to a referral for diagnostic assessment. If left untreated these disorders are associated with long-term negative outcomes including substance abuse and increased risk for suicide. This paper presents a new approach for identifying children with internalizing disorders using an instrumented 90-second mood induction task. Participant motion during the task is monitored using a commercially available wearable sensor. We show that machine learning can be used to differentiate children with an internalizing diagnosis from controls with 81% accuracy (67% sensitivity, 88% specificity). We provide a detailed description of the modeling methodology used to arrive at these results and explore further the predictive ability of each temporal phase of the mood induction task. Kinematical measures most discriminative of internalizing diagnosis are analyzed in detail, showing affected children exhibit significantly more avoidance of ambiguous threat. Performance of the proposed approach is compared to clinical thresholds on parent-reported child symptoms which differentiate children with an internalizing diagnosis from controls with slightly lower accuracy (.68-.75 vs. .81), slightly higher specificity (.88-1.00 vs. .88), and lower sensitivity (.00-.42 vs. .67) than the proposed, instrumented method. These results point toward the future use of this approach for screening children for internalizing disorders so that interventions can be deployed when they have the highest chance for long-term success.

The Development of Mood Repair Response Repertories: I. Age-Related Changes Among 7- to 14-Year-Old Depressed and Control Children and Adolescents.

The purpose of this study was to test developmentally informed hypotheses about regulatory responses to sadness that attenuate versus exacerbate it (adaptive versus maladaptive mood repair responses, respectively) across late childhood, early adolescence, and mid-adolescence. In a multi-site study in Hungary, clinic-based, 7- to 14-year-olds with Diagnostic and Statistical Manual of Mental Disorders' (4th ed., text rev.) depressive disorders (N = 697; 55% male) and age/sex matched (at 1:2) nondepressed, school-based controls (N = 1,394) reported on their usual responses to sadness/dysphoria; parental reports were obtained separately. Adaptive and maladaptive response repertoire scores were compared across ages within and across subject groups, and by informant, controlling for confounds. Contrary to Hypothesis 1, older (vs. younger) youths in both groups reported fewer adaptive regulatory responses. Maladaptive response repertoires were unrelated to age among controls but significantly increased with age among depressed youths, particularly the girls. Partially supporting Hypothesis 2, subject groups differed in age-related trajectories of mood repair repertories, but not as expected (e.g., younger depressed children reported larger adaptive response repertoires than did controls). Parental reports revealed no developmental changes in offspring's mood repair repertories. Parent-offspring reports were most discordant for younger (vs. older) offspring, tended to converge around age 11, and were consistently and significantly larger in the depressed sample. Self-reported adaptive mood repair repertories appear to have been laid down by late childhood and then undergo "trimming" across ages 7-14 years. The extensive maladaptive mood repair response repertoires of depressed youths, which increased with age, distinguish them primarily from controls. Therefore, reducing maladaptive regulatory responses to sadness should be a priority when treating depressed youths.

Developmental influences on stress response systems: Implications for psychopathology vulnerability in adolescence.

The adolescent transition is marked by increases in stress exposure and significant maturation of neural and hormonal stress processing systems. Variability in the development of these systems during adolescence may influence the risk for stress-related psychopathology. This paper aims to review the developmental maturation of the HPA axis and related stress regulation systems, and demonstrate how interference in this adaptive developmental process may increase the risk for negative outcomes. We argue that the developmental maturation of the HPA axis aims to improve the regulatory capacity of the axis in order to more adaptively respond to these increases in stress reactivity. Additionally, we review evidence that sex differences in the development of the HPA and related axes may contribute to sex differences in the risk for stress-related psychopathology. Finally, we discuss how contextual factors, such as early trauma and obesity may alter the development of HPA axis during the adolescence transition and how alterations of normative development increase the risk for stress-related disorders.