The Adolescent Brain Cognitive Development (ABCD) Study is the largest U.S.-based neuroimaging initiative of adolescent brain maturation. Diffusion MRI (dMRI) provides unique insights into white matter organization, yet applying advanced processing pipelines and managing technical variability across scanning environments remains challenging at scale. To address these issues, we present ABCD-BIDS Community Collection (ABCC) release 3.1.0, including a curated resource of more than 24,000 fully processed ABCD dMRI datasets. ABCC provides fully processed images, nuanced image quality metrics, advanced microstructural measures, and person-specific bundle tractography. Evaluating these rich data revealed that measures of diffusion restriction and non-Gaussianity—in particular the intracellular volume fraction from NODDI and return-to-origin probability from MAP-MRI—were highly sensitive to neurodevelopment and robust to variation in image quality. Additionally, harmonization of microstructural features markedly improved the cross-vendor generalizability of developmental effects. Together, ABCC accelerates reproducible, rigorous research on adolescent white matter development.

Background: Adolescence is a developmental period involving ongoing white matter (WM) maturation and rising risk for psychopathology. This risk is particularly elevated among youth whose parents have mental health problems. Methods: Leveraging longitudinal data from three waves of the community-based Adolescent Brain Cognitive Development (ABCD) Study (N = 6,581, Nobservations = 16, 271, mean ageTP 1 = 10.2, mean ageTP 2 = 12.0 , mean ageTP 3 = 14.2), we employed random intercept cross-lagged panel models (RI-CLPMs) to disentangle stable between-person differences from time-varying within-person changes. We examined prospective and bidirectional associations between youth general psychopathology and diffusion metrics, including fractional anisotropy (FA) and mean diffusivity (MD) in the uncinate fasciculus (UF), superior longitudinal fasciculus (SLF), and corpus callosum (CC). We also tested whether parental psychopathology moderated these associations. Results: Preregistered analyses showed no significant between-person or within-person associations between parent-reported youth psychopathology and WM microstructure, nor evidence of moderation by parental psychopathology. In exploratory analyses using youth self-reports, SLF and CC FA were negatively associated with psychopathology at the between-person level, but positively associated at the within-person level during early adolescence. Additionally, SLF and CC MD were negatively associated with self-reported psychopathology on the within-person level during early adolescence, with this association persisting into mid-adolescence for the CC. Parental psychopathology moderated the within-person association between CC MD and self-reported youth psychopathology. Conclusion: Overall, the findings did not support hypothesized prospective and bidirectional associations between parent-reported youth psychopathology and WM microstructure, nor moderation by parental psychopathology. Instead, our findings highlight limitations of tract-specific explanations for general psychopathology in at-risk youth, informant discrepancies, and the importance of separating between- and within-person effects.

Early-life adversity is pervasive worldwide and represents a potent risk factor for increased mental health burden across the lifespan. However, there is substantial individual heterogeneity in associations between adversity exposure, neurobiological changes, and mental health problems. Accounting for key features of adversity such as the developmental timing of exposure may clarify associations between adversity, neurodevelopment, and mental health. The present study leverages sparse canonical correlation analysis to characterize modes of covariation between age of adversity exposure and the integrity of white matter tracts throughout the brain in a sample of 107 adults. We find that adversity exposure during middle childhood (ages 5-6 and 8-9 in particular) is consistently linked with alterations in white matter tract integrity, such that tracts supporting sensorimotor functions display higher integrity in relation to adversity exposure while tracts supporting cortico-cortical communication display lower integrity. Further, latent patterns of tract integrity linked with adversity experienced across preschool age and middle childhood (ages 4-9) were associated with trauma-related symptoms in adulthood. Our findings underscore that adversity exposure may differentially affect white matter in a function- and developmental-timing specific manner and suggest that adversity experienced between ages 4-9 may shape the development of global white matter tracts in ways that are relevant for adult mental health.

Parsing heterogeneity in the nature of adversity exposure and neurobiological functioning may facilitate better understanding of how adversity shapes individual variation in risk for and resilience against anxiety. One putative mechanism linking adversity exposure with anxiety is disrupted threat and safety learning. Here, we applied a person-centered approach (latent profile analysis) to characterize patterns of adversity exposure at specific developmental stages and threat/safety discrimination in corticolimbic circuitry in 120 young adults. We then compared how the resultant profiles differed in anxiety symptoms. Three latent profiles emerged: (1) a group with lower lifetime adversity, higher neural activation to threat, and lower neural activation to safety; (2) a group with moderate adversity during middle childhood and adolescence, lower neural activation to threat, and higher neural activation to safety; and (3) a group with higher lifetime adversity exposure and minimal neural activation to both threat and safety. Individuals in the second profile had lower anxiety than the other profiles. These findings demonstrate how variability in within-person combinations of adversity exposure and neural threat/safety discrimination can differentially relate to anxiety, and suggest that for some individuals, moderate adversity exposure during middle childhood and adolescence could be associated with processes that foster resilience to future anxiety.

BACKGROUND: Neighborhood-or area-level socioeconomic disadvantage is associated with neural alterations across the life span. However, few studies have examined the effects of neighborhood disadvantage on white matter microstructure during adolescence, an important period of development that coincides with increased risk for psychopathology.METHODS: In 200 adolescents (ages 13-20 years; 54.5% female, 4% nonbinary) recruited from 2 studies enriched for early adversity and depression, we examined whether neighborhood socioeconomic disadvantage derived from census tract data was related to white matter microstructure in several major white matter tracts. We also examined whether depressive symptoms and sex moderated these associations.RESULTS: Greater neighborhood socioeconomic disadvantage was associated with lower fractional anisotropy (FA) in the left arcuate fasciculus (3 =-0.24, false discovery rate [FDR]-corrected p = .035) and right uncinate fasciculus (3 =-0.32, FDR-corrected p = .002) above and beyond the effects of family-level socioeconomic status. Depressive symptoms significantly moderated the association between left arcuate fasciculus FA and both neighborhood (3 = 0.17, FDR-corrected p = .026) and unemployment (3 = 0.22, FDR-corrected p = .004) disadvantage such that these associations were only significant in adolescents who reported less severe depression. Sex did not moderate the association between socioeconomic disadvantage and FA in these tracts.CONCLUSIONS: Greater neighborhood socioeconomic disadvantage, particularly poverty and educational attainment levels, was associated with lower FA in the arcuate fasciculus and uncinate fasciculus above and beyond the effects of family-level measures of socioeconomic status. These patterns were only observed in adolescents with low levels of depression, suggesting that we must be cautious about generalizing these findings to youths who struggle with mental health difficulties.

Since the landmark Adverse Childhood Experiences (ACEs) study, adversity research has expanded to more precisely account for the multifaceted nature of adverse experiences. The complex data structures and interrelated nature of adversity data require robust multivariate statistical methods, and recent methodological and statistical innovations have facilitated advancements in research on childhood adversity. Here, we provide an overview of a subset of multivariate methods that we believe hold particular promise for advancing the field's understanding of early-life adversity, and discuss how these approaches can be practically applied to explore different research questions. This review covers data-driven or unsupervised approaches (including dimensionality reduction and person-centered clustering/subtype identification) as well as supervised/prediction-based approaches (including linear and tree-based models and neural networks). For each, we highlight studies that have effectively applied the method to provide novel insight into early-life adversity. Taken together, we hope this review serves as a resource to adversity researchers looking to expand upon the cumulative approach described in the original ACEs study, thereby advancing the field's understanding of the complexity of adversity and related developmental consequences.

Though stress is a ubiquitous experience across the lifespan, exposure to stress during infancy, childhood, and adolescence – when development is especially pronounced – has particularly salient effects on the developing brain and behavior. We review current theory regarding typical development of the neurobiological systems underlying the stress response in humans. Against this backdrop, we highlight ways in which exposure to stress can manifest in altered neurobiological development, focusing on implications for the development of frontolimbic circuitry. We emphasize the importance of harnessing a dimensional approach to investigating the impact of stress exposure and describe three features of stress exposure – stressor type, caregiver involvement, and developmental timing – as particularly important factors that may help to elucidate more precise mechanisms by which stress affects the developing brain. Finally, we review methodological considerations for further study of the neurobiological systems underlying stress and coping, and briefly review implications for both clinical practice and policy.

Key theoretical frameworks have proposed that examining the impact of exposure to specific dimensions of stress at specific developmental periods is likely to yield important insight into processes of risk and resilience. Utilizing a sample of N = 549 young adults who provided a detailed retrospective history of their lifetime exposure to numerous dimensions of traumatic stress and ratings of their current trauma-related symptomatology via completion of an online survey, here we test whether an individual's perception of their lifetime stress as either controllable or predictable buffered the impact of exposure on trauma-related symptomatology assessed in adulthood. Further, we tested whether this moderation effect differed when evaluated in the context of early childhood, middle childhood, adolescence, and young adulthood stress. Consistent with hypotheses, results highlight both stressor controllability and stressor predictability as buffering the impact of traumatic stress exposure on trauma-related symptomatology and suggest that the potency of this buffering effect varies across unique developmental periods. Leveraging dimensional ratings of lifetime stress exposure to probe heterogeneity in outcomes following stress - and, critically, considering interactions between dimensions of exposure and the developmental period when stress occurred - is likely to yield increased understanding of risk and resilience following traumatic stress.

Exposure to socioeconomic disadvantages (SED) can have negative impacts on mental health, yet SED are a multifaceted construct and the precise processes by which SED confer deleterious effects are less clear. Using a large and diverse sample of preadolescents (ages 9-10 years at baseline, n = 4038, 49% female) from the Adolescent Brain Cognitive Development Study, we examined associations among SED at both household (i.e., income-needs and material hardship) and neighborhood (i.e., area deprivation and neighborhood unsafety) levels, frontoamygdala resting-state functional connectivity, and internalizing symptoms at baseline and 1-year follow-up. SED were positively associated with internalizing symptoms at baseline and indirectly predicted symptoms 1 year later through elevated symptoms at baseline. At the household level, youth in households characterized by higher disadvantage (i.e., lower income-to-needs ratio) exhibited more strongly negative frontoamygdala coupling, particularly between the bilateral amygdala and medial OFC (mOFC) regions within the frontoparietal network. Although more strongly positive amygdala-mOFC coupling was associated with higher levels of internalizing symptoms at baseline and 1-year follow-up, it did not mediate the association between income-to-needs ratio and internalizing symptoms. However, at the neighborhood level, amygdala-mOFC functional coupling moderated the effect of neighborhood deprivation on internalizing symptoms. Specifically, higher neighborhood deprivation was associated with higher internalizing symptoms for youth with more strongly positive connectivity, but not for youth with more strongly negative connectivity, suggesting a potential buffering effect. Findings highlight the importance of capturing multilevel socioecological contexts in which youth develop to identify youth who are most likely to benefit from early interventions.

Adolescent depression is characterized by heightened inflammation and altered connectivity of fronto-cingulatelimbic tracts, including the genu of the corpus callosum (CCG) and the uncinate fasciculus (UF). No studies, however, have yet examined the association between inflammation, measured by peripheral levels of cytokines, and white matter connectivity of fronto-cingulate-limbic tracts in adolescents. Here, 56 depressed adolescents (32 females, 3 non-binary; 16.23 +/- 1.28 years) and 19 controls (10 females; 15.72 +/- 1.17 years) completed a diffusion-weighted MRI scan at 3 Tesla. We conducted deterministic tractography to segment bilateral corpus callosum (genu and splenium) and UF and computed mean fractional anisotropy (FA) in each tract. A subset of participants (43 depressed and 17 healthy controls) also provided dried blood spot samples from which we assayed interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) using a Luminex multiplex array. Depressed participants did not differ from controls in FA of the corpus callosum or UF (all FDR-corrected ps > 0.056) but exhibited higher levels of inflammation than did controls (IL-6: 13 = 0.91, FDR-corrected p = 0.006; TNF-alpha: 13 = 0.76, FDR-corrected p = 0.006). Although diagnostic group did not moderate the associations between inflammatory cytokines and FA in the CCG and UF, across both groups, greater peripheral inflammation was associated with lower FA in the CCG (IL-6: 13 = -0.38; FDR-corrected p = 0.044; TNF-alpha: 13 = -0.41, FDR-corrected p = 0.044). This study is the first to examine associations between peripheral inflammation and white matter microstructure of fronto-cingulate-limbic tracts in depressed and nondepressed adolescents. Future mechanistic studies are needed to confirm our findings; nevertheless, our results suggest that heightened inflammation is an important component of neurophenotypes that are relevant to adolescent depression.

Adolescence is marked by heightened stress exposure and psychopathology, but also vast potential for opportunity. We highlight how researchers can leverage both developmental and individual differences in stress responding and corticolimbic circuitry to optimize interventions during this unique developmental period.

Microstructural remodeling of white matter pathways represents one potential mechanism linking childhood stress exposure with mental health across development. However, the degree to which specific aspects of stress exposure—such as the type or developmental timing of a stressor—may uniquely impact developing white matter has yet to be elucidated. Delineating links between early-life stress, neurobiology, and psychopathology is critical to developing targeted interventions and identifying trajectories of risk following stress exposure to inform prevention efforts.

Early-life experiences play a profound role in conferring risk and resilience. However, there is vast heterogeneity in the nature of early experiences and in child and adolescent outcomes following adversity. Increasingly, dimensional approaches have focused on delineating how specific features of the early environment may differentially shape the developing brain and risk for psychiatric disorders.

The endocannabinoid system is an important regulator of emotional responses such as fear, and a number of studies have implicated endocannabinoid signaling in anxiety. The fatty acid amide hydrolase (FAAH) C385A polymorphism, which is associated with enhanced endocannabinoid signaling in the brain, has been identified across species as a potential protective factor from anxiety. In particular, adults with the variant FAAH 385A allele have greater fronto‐amygdala connectivity and lower anxiety symptoms. Whether broader network‐level differences in connectivity exist, and when during development this neural phenotype emerges, remains unknown and represents an important next step in understanding how the FAAH C385A polymorphism impacts neurodevelopment and risk for anxiety disorders. Here, we leveraged data from 3,109 participants in the nationwide Adolescent Brain Cognitive Development Study℠ (10.04 ± 0.62 years old; 44.23% female, 55.77% male) and a cross‐validated, data‐driven approach to examine associations between genetic variation and large‐scale resting‐state brain networks. Our findings revealed a distributed brain network, comprising functional connections that were both significantly greater (95% CI for p values = [<0.001, <0.001]) and lesser (95% CI for p values = [0.006, <0.001]) in A‐allele carriers relative to non‐carriers. Furthermore, there was a significant interaction between genotype and the summarized connectivity of functional connections that were greater in A‐allele carriers, such that non‐carriers with connectivity more similar to A‐allele carriers (i.e., greater connectivity) had lower anxiety symptoms ( β = −0.041, p = 0.030). These findings provide novel evidence of network‐level changes in neural connectivity associated with genetic variation in endocannabinoid signaling and suggest that genotype‐associated neural differences may emerge at a younger age than genotype‐associated differences in anxiety.

Children make up over half of the world's migrants and refugees and face a multitude of traumatic experiences prior to, during, and following migration. Here, we focus on migrant children emigrating from Mexico and Central America to the United States and review trauma related to migration, as well as its implications for the mental health of migrant and refugee children. We then draw upon the early adversity literature to highlight potential behavioral and neurobiological sequalae of migration-related trauma exposure, focusing on attachment, emotion regulation, and fear learning and extinction as transdiagnostic mechanisms underlying the development of internalizing and externalizing symptomatology following early-life adversity. This review underscores the need for interdisciplinary efforts to both mitigate the effects of trauma faced by migrant and refugee youth emigrating from Mexico and Central America and, of primary importance, to prevent child exposure to trauma in the context of migration. Thus, we conclude by outlining policy recommendations aimed at improving the mental health of migrant and refugee youth.

Depression is a chronic and debilitating condition that often emerges during adolescence, a period of significant brain maturation. Few studies, however, have examined how mechanisms of neuroplasticity, including myelination, are affected by adolescent-onset depression. Here, we used multimodal MR imaging to characterize myelin, indexed by R1, in white matter tracts previously associated with depression and compare 48 adolescents with lifetime depression (45 with current depression, 3 remitted) and 35 healthy controls in R1. Compared to healthy controls, R1 was higher in adolescents with lifetime depression in the uncinate fasciculus and corpus callosum genu (all βs > 0.42; all ps < 0.037). Sex significantly moderated the association between depression and R1 in the left uncinate fasciculus and corpus callosum genu (all βs > 0.86; all ps < 0.02), such that depressed female adolescents had significantly higher R1 in these tracts than did healthy female adolescents (all βs > 0.82; all ps < 0.0012). In contrast, depressed and non-depressed male adolescents did not differ in R1 in these tracts (all ps > 0.32). While fractional anisotropy (FA), a commonly examined measure of white matter organization based on diffusion-weighted MRI, in the left uncinate was positively associated with lifetime depression in our sample (β = 0.56; p = 0.016), we found no evidence of sex-specific effects of depression in FA. Our results suggest that R1 is more sensitive to sex-specific effects of depression than FA, particularly in female adolescents. Given evidence that myelin inhibits synapse formation and reduces brain plasticity, our findings implicate experience-driven regional myelination as a mechanism underlying depression during periods of significant neural maturation such as adolescence.

Traumatic early-life experiences can have lasting effects on brain and behavior, including altered functional connectivity. However, it remains unclear whether trauma-related patterns of altered connectivity can be observed in children, and whether individual differences in connectivity can predict psychopathology symptoms. Clarifying these links could provide insight into the etiology of trauma-related brain changes, and their relation to psychiatric symptoms.

Adolescence is a period of dynamic change across multiple systems. Concurrent maturation of neural, biological, and psychosocial functioning renders adolescence a time of heightened sensitivity to both negative and positive experiences. Here, we review recent literature across these domains, discuss risk and opportunity in the context of ongoing neural development, and highlight promising directions for future research. Finally, we propose that conceptualizing adolescence as a sensitive window during which plasticity across multiple systems is enhanced may support the identification of links between experience, neurodevelopment, and psychopathology.