Environmental and neurodevelopmental contributors to youth mental illness.

While a myriad of factors likely contribute to the development of mental illness in young people, the social environment (including early adverse experiences) in concert with neurodevelopmental alterations is undeniably important. A number of influential theories make predictions about how and why neurodevelopmental alterations may mediate or moderate the effects of the social environment on the emergence of mental illness. Here, we discuss current evidence supporting each of these theories. Although this area of research is rapidly growing, the body of evidence is still relatively limited. However, there exist some consistent findings, including increased striatal reactivity during positive affective processing and larger hippocampal volumes being associated with increased vulnerability or susceptibility to the effects of social environments on internalizing symptoms. Limited longitudinal work has investigated neurodevelopmental mechanisms linking the social environment with mental health. Drawing from human research and insights from animal studies, we propose an integrated mediation-moderation model and outline future research directions to advance the field.

The influence of maternal and paternal parenting on adolescent brain structure.

BACKGROUND: Adolescents raised in families with different maternal and paternal parenting combinations exhibit variations in neurocognition and psychopathology; however, whether neural differences exist remains unexplored. This study used a longitudinal twin sample to delineate how different parenting combinations influence adolescent brain structure and to elucidate the genetic contribution. METHODS: A cohort of 216 twins participated in parenting assessments during early adolescence and underwent MRI scanning during middle adolescence. We utilized latent profile analysis to distinguish between various maternal and paternal parenting profiles and subsequently investigated their influences on brain anatomy. Biometric analysis was applied to assess the genetic influences on brain structure, and associations with internalizing symptoms were explored. RESULTS: In early adolescence, four parenting profiles emerged characterized by levels of harshness and hostility in one or both parents. Compared to adolescents in "catparent" families (low harshness/hostility in both parents), those raised in "tigermom" families (harsh/hostile mother only) exhibited smaller nucleus accumbens volume and larger temporal cortex surface area; those in "tigerdad" families demonstrated larger thalamus volumes; those in "tigerparent" families displayed smaller volumes in the mid-anterior corpus callosum. Genetic risk factors contributed significantly to the observed brain structural heterogeneity and internalizing symptoms. However, the influences of parenting profiles and brain structure on internalizing symptoms were not significant. CONCLUSIONS: The findings underscore distinct brain structural features linked to maternal and paternal parenting combinations, particularly in terms of subcortical volume and cortical surface area. This study suggests an interdependent role of maternal and paternal parenting in shaping adolescent neurodevelopment.

Patterns of Melatonin Use in a Diverse National Pediatric Sample.

This cohort study examines patterns of melatonin use among participants in the Adolescent Brain Cognitive Development (ABCD) Study and characterizes factors associated with use.

The promise and pitfalls of a strength-based approach to child poverty and neurocognitive development: Implications for policy.

There has been significant progress in understanding the effects of childhood poverty on neurocognitive development. This progress has captured the attention of policymakers and promoted progressive policy reform. However, the prevailing emphasis on the harms associated with childhood poverty may have inadvertently perpetuated a deficit-based narrative, focused on the presumed shortcomings of children and families in poverty. This focus can have unintended consequences for policy (e.g., overlooking strengths) as well as public discourse (e.g., focusing on individual rather than systemic factors). Here, we join scientists across disciplines in arguing for a more well-rounded, "strength-based" approach, which incorporates the positive and/or adaptive developmental responses to experiences of social disadvantage. Specifically, we first show the value of this approach in understanding normative brain development across diverse human environments. We then highlight its application to educational and social policy, explore pitfalls and ethical considerations, and offer practical solutions to conducting strength-based research responsibly. Our paper re-ignites old and recent calls for a strength-based paradigm shift, with a focus on its application to developmental cognitive neuroscience. We also offer a unique perspective from a new generation of early-career researchers engaged in this work, several of whom themselves have grown up in conditions of poverty. Ultimately, we argue that a balanced strength-based scientific approach will be essential to building more effective policies.

Investigating Associations Between Maternal Behavior and the Development of Functional Connectivity During the Transition From Late Childhood to Early Adolescence.

BACKGROUND: Parenting behavior is thought to affect child brain development, with implications for mental health. However, longitudinal studies that use whole-brain approaches are lacking. In this study, we investigated associations between parenting behavior, age-related changes in whole-brain functional connectivity, and psychopathology symptoms in children and adolescents. METHODS: Two hundred forty (126 female) children underwent resting-state functional magnetic resonance imaging at up to two time points, providing a total of 398 scans covering the age range 8 to 13 years. Parenting behavior was self-reported at baseline. Parenting factors (positive parenting, inattentive parenting, and harsh and inconsistent discipline) were identified based on a factor analysis of self-report parenting questionnaires. Longitudinal measures of child internalizing and externalizing symptoms were collected. Network-based R-statistics was used to identify associations between parenting and age-related changes in functional connectivity. RESULTS: Higher maternal inattentive behavior was associated with lower decreases in connectivity over time, particularly between regions of the ventral attention and default mode networks and frontoparietal and default mode networks. However, this association was not significant after strict correction for multiple comparisons. CONCLUSIONS: While results should be considered preliminary, they suggest that inattentive parenting may be associated with a reduction in the normative pattern of increased network specialization that occurs with age. This may reflect a delayed development of functional connectivity.

Linking Polygenic Risk of Schizophrenia to Variation in Magnetic Resonance Imaging Brain Measures: A Comprehensive Systematic Review.

BACKGROUND AND HYPOTHESIS: Schizophrenia is highly heritable, with a polygenic effect of many genes conferring risk. Evidence on whether cumulative risk also predicts alterations in brain morphology and function is inconsistent. This systematic review examined evidence for schizophrenia polygenic risk score (sczPRS) associations with commonly used magnetic resonance imaging (MRI) measures. We expected consistent evidence to emerge for significant sczPRS associations with variation in structure and function, specifically in frontal, temporal, and insula cortices that are commonly implicated in schizophrenia pathophysiology. STUDY DESIGN: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched MEDLINE, Embase, and PsycINFO for peer-reviewed studies published between January 2013 and March 2022. Studies were screened against predetermined criteria and National Institutes of Health (NIH) quality assessment tools. STUDY RESULTS: In total, 57 studies of T1-weighted structural, diffusion, and functional MRI were included (age range = 9-80 years, Nrange = 64-76 644). We observed moderate, albeit preliminary, evidence for higher sczPRS predicting global reductions in cortical thickness and widespread variation in functional connectivity, and to a lesser extent, region-specific reductions in frontal and temporal volume and thickness. Conversely, sczPRS does not predict whole-brain surface area or gray/white matter volume. Limited evidence emerged for sczPRS associations with diffusion tensor measures of white matter microstructure in a large community sample and smaller cohorts of children and young adults. These findings were broadly consistent across community and clinical populations. CONCLUSIONS: Our review supports the hypothesis that schizophrenia is a disorder of disrupted within and between-region brain connectivity, and points to specific whole-brain and regional MRI metrics that may provide useful intermediate phenotypes.

Neurobiological correlates of resilience during childhood and adolescence - A systematic review.

Research examining the neurobiological mechanisms of resilience has grown rapidly over the past decade. However, there is vast heterogeneity in research study design, methods, and in how resilience is operationalized, making it difficult to gauge what we currently know about resilience biomarkers. This preregistered systematic review aimed to review and synthesize the extant literature to identify neurobiological correlates of resilience to adversity during childhood and adolescence. Literature searches on MEDLINE and PsycINFO yielded 3834 studies and a total of 49 studies were included in the final review. Findings were synthesized based on how resilience was conceptualized (e.g., absence of psychopathology, trait resilience), and where relevant, the type of outcome examined (e.g., internalizing symptoms, post-traumatic stress disorder). Our synthesis showed that findings were generally mixed. Nevertheless, some consistent findings suggest that resilience neural mechanisms may involve prefrontal and subcortical regions structure/activity, as well as connectivity between these regions. Given substantial heterogeneity in the definition and operationalization of resilience, more methodological consistency across studies is required for advancing knowledge in this field.

The neural, stress hormone and inflammatory correlates of childhood deprivation and threat in psychosis: A systematic review.

Childhood adversity increases the risk of developing psychosis, but the biological mechanisms involved are unknown. Disaggregating early adverse experiences into core dimensions of deprivation and threat may help to elucidate these mechanisms. We therefore systematically searched the literature investigating associations between deprivation and threat, and neural, immune and stress hormone systems in individuals on the psychosis spectrum. Our search yielded 74 articles, from which we extracted and synthesized relevant findings. While study designs were heterogeneous and findings inconsistent, some trends emerged. In psychosis, deprivation tended to correlate with lower global cortical volume, and some evidence supported threat-related variation in prefrontal cortex morphology. Greater threat exposure was also associated with higher C-reactive protein, and higher and lower cortisol measures. When examined, associations in controls were less evident. Overall, findings indicate that deprivation and threat may associate with partially distinct biological mechanisms in the psychosis spectrum, and that associations may be stronger than in controls. Dimensional approaches may help disentangle the biological correlates of childhood adversity in psychosis, but more studies are needed.

A longitudinal study of childhood maltreatment, subcortical development, and subcortico-cortical structural maturational coupling from early to late adolescence.

BACKGROUND: Examining neurobiological mechanisms that may transmit the effects of childhood maltreatment on mental health in youth is crucial for understanding vulnerability to psychopathology. This study investigated associations between childhood maltreatment, adolescent structural brain development, and mental health trajectories into young-adulthood. METHODS: Structural magnetic resonance imaging data was acquired from 144 youth at three time points (age 12, 16, and 18 years). Childhood maltreatment was reported to occur prior to the first scan. Linear mixed models were utilized to examine the association between total childhood maltreatment, neglect, abuse and (i) amygdala and hippocampal volume development, and (ii) maturational coupling between amygdala/hippocampus volume and the thickness of prefrontal regions. We also examined whether brain development mediated the association between maltreatment and depressive and anxiety symptoms trajectories from age 12 to 28. RESULTS: Total maltreatment, and neglect, were associated with positive maturational coupling between the amygdala and caudal anterior cingulate cortex (cACC), whereby at higher and lower levels of amygdala growth, maltreatment was associated with lower and higher PFC thinning, respectively. Neglect was also associated with maturational coupling of the hippocampus with prefrontal regions. While positive amygdala-cACC maturational coupling was associated with greater increases in anxiety symptoms, it did not significantly mediate the association between maltreatment and anxiety symptom trajectories. CONCLUSION: We found maltreatment to be associated with altered patterns of coupling between subcortical and prefrontal regions during adolescence, suggesting that maltreatment is associated with the development of socio-emotional neural circuitry. The implications of these findings for mental health require further investigation.

Childhood socioeconomic status and the pace of structural neurodevelopment: accelerated, delayed, or simply different?

Socioeconomic status (SES) is associated with children's brain and behavioral development. Several theories propose that early experiences of adversity or low SES can alter the pace of neurodevelopment during childhood and adolescence. These theories make contrasting predictions about whether adverse experiences and low SES are associated with accelerated or delayed neurodevelopment. We contextualize these predictions within the context of normative development of cortical and subcortical structure and review existing evidence on SES and structural brain development to adjudicate between competing hypotheses. Although none of these theories are fully consistent with observed SES-related differences in brain development, existing evidence suggests that low SES is associated with brain structure trajectories more consistent with a delayed or simply different developmental pattern than an acceleration in neurodevelopment.

Longitudinal changes in within-salience network functional connectivity mediate the relationship between childhood abuse and neglect, and mental health during adolescence.

BACKGROUND: Understanding the neurobiological underpinnings of childhood maltreatment is vital given consistent links with poor mental health. Dimensional models of adversity purport that different types of adversity likely have distinct neurobiological consequences. Adolescence is a key developmental period, during which deviations from normative neurodevelopment may have particular relevance for mental health. However, longitudinal work examining links between different forms of maltreatment, neurodevelopment, and mental health is limited. METHODS: In the present study, we explored associations between abuse, neglect, and longitudinal development of within-network functional connectivity of the salience (SN), default mode (DMN), and executive control network in 142 community residing adolescents. Resting-state fMRI data were acquired at age 16 (T1; M = 16.46 years, s.d. = 0.52, 66F) and 19 (T2; mean follow-up period: 2.35 years). Mental health data were also collected at T1 and T2. Childhood maltreatment history was assessed prior to T1. RESULTS: Abuse and neglect were both found to be associated with increases in within-SN functional connectivity from age 16 to 19. Further, there were sex differences in the association between neglect and changes in within-DMN connectivity. Finally, increases in within-SN connectivity were found to mediate the association between abuse/neglect and lower problematic substance use and higher depressive symptoms at age 19. CONCLUSIONS: Our findings suggest that childhood maltreatment is associated with altered neurodevelopmental trajectories, and that changes in salience processing may be linked with risk and resilience for the development of depression and substance use problems during adolescence, respectively. Further work is needed to understand the distinct neurodevelopmental and mental health outcomes of abuse and neglect.

The Role of School Environment in Brain Structure, Connectivity, and Mental Health in Children: A Multimodal Investigation.

BACKGROUND: Much work has been dedicated to understanding the effects of adverse home environments on brain development. While the school social and learning environment plays a role in child development, little work has been done to investigate the impact of the school environment on the developing brain. The goal of the present study was to examine associations between the school environment, brain structure and connectivity, and mental health. METHODS: In this preregistered study we investigated these questions in a large sample of adolescents (9-10 years of age) from the Adolescent Brain Cognitive Development (ABCD) Study. We examined the association between school environment and gray matter (n = 10,435) and white matter (n = 10,770) structure and functional connectivity (n = 9528). We then investigated multivariate relationships between school-associated brain measures and mental health. RESULTS: School environment was associated with connectivity of the auditory and retrosplenial temporal network as well as of higher-order cognitive networks like the cingulo-opercular, default mode, ventral attention, and frontoparietal networks. Multivariate analyses revealed that connectivity of the cingulo-opercular and default mode networks was also associated with mental health. CONCLUSIONS: Findings shed light on the neural mechanisms through which favorable school environments may contribute to positive mental health outcomes in children. Our findings have implications for interventions targeted at promoting positive youth functioning through improving school environments.

The role of school connectedness in the prevention of youth depression and anxiety: a systematic review with youth consultation.

BACKGROUND: School connectedness reflects the quality of students' engagement with peers, teachers, and learning in the school environment. It has attracted attention from both the health and education sectors as a potentially modifiable protective factor for common mental health problems. However, the extent to which school connectedness may prevent the onset of youth depression or anxiety or promote their remission is unclear. This systematic review examined evidence for prospective relationships between school connectedness and depression and anxiety, and the effect of interventions to improve school connectedness on depression and anxiety. METHODS: We searched MEDLINE, PsycINFO, PubMed, and ERIC electronic databases for peer-reviewed quantitative longitudinal, or intervention studies published from 2011-21 in English examining relationships between school connectedness and anxiety and/or depression. Participants were 14-24 years old when depression and anxiety outcomes were assessed in any education setting in any country. We partnered with five youth advisers (aged 16-21 years) with lived experience of mental health problems and/or the schooling system in Australia, Indonesia, and the Philippines to ensure that youth perspectives informed the review. RESULTS: Our search identified 3552 unique records from which 34 longitudinal and 2 intervention studies were ultimately included. Studies were primarily from the United States of America (69.4%). Depression and anxiety outcomes were first measured at 14 years old, on average. Most studies found a significant protective relationship between higher levels of school connectedness and depressive and/or anxiety symptoms; more measured depression than anxiety. A few studies found a non-significant relationship. Both intervention studies designed to increase school connectedness improved depression, one through improvements in self-esteem and one through improvements in relationships at school. CONCLUSIONS: These findings suggest that school connectedness may be a novel target for the prevention of depression and anxiety. We were not able to determine whether improving school connectedness promotes remission in young people already experiencing depression and anxiety. More studies examining anxiety, diagnostic outcomes, and beyond North America are warranted, as well as intervention trials. TRIAL REGISTRATION: PROSPERO 2021 CRD42021270967.

Assessment of Parent Income and Education, Neighborhood Disadvantage, and Child Brain Structure.

Importance: Although different aspects of socioeconomic status (SES) may represent distinct risk factors for poor mental health in children, knowledge of their differential and synergistic associations with the brain is limited. Objective: To examine the independent associations between distinct SES factors and child brain structure. Design, Setting, and Participants: We used baseline data from participants aged 9 to 10 years in the Adolescent Brain Cognitive Development (ABCD) study. These data were collected from 21 US sites between September 2017 and August 2018. Study participants were recruited from schools to create a participant sample that closely reflects the US population. Exposures: Neighborhood disadvantage was measured using the area deprivation index. We also used data on total parent or caregiver educational attainment (in years) and household income-to-needs ratio. Main Outcomes and Measures: T1-weighted magnetic resonance imaging was used to assess measures of cortical thickness, surface area, and subcortical volume. Results: Data from 8862 ABCD participants aged 9 to 10 years were analyzed. The mean (SD) age was 119.1 (7.5) months; there were 4243 girls (47.9%) and 4619 boys (52.1%). Data on race or ethnicity were available for 8857 of 8862 participants: 173 (2.0%) were Asian, 1099 (12.4%) were Black or African American, 1688 (19.1%) were Hispanic, 4967 (56.1%) were White, and 930 (10.5%) reported multiple races or ethnicities. Using 10-fold, within-sample split-half replication, we found that neighborhood disadvantage was associated with lower cortical thickness in the following brain regions (η2 = 0.004-0.009): cuneus (B [SE] = -0.099 [0.013]; P < .001), lateral occipital (B [SE] = -0.088 [0.011]; P < .001), lateral orbitofrontal (B [SE] = -0.072 [0.012]; P < .001), lingual (B [SE] = -0.104 [0.012]; P < .001), paracentral (B [SE] = -0.086 [0.012]; P < .001), pericalcarine (B [SE] = -0.077 [0.012]; P < .001), postcentral (B [SE] = -0.069 [0.012]; P < .001), precentral (B [SE] = -0.059 [0.011]; P < .001), rostral middle frontal (B [SE] = -0.076 [0.011]; P < .001), and superior parietal (B [SE] = -0.060 [0.011]; P < .001). Exploratory analyses showed that the associations of low educational attainment or neighborhood disadvantage and low cortical thickness were attenuated in the presence of a high income-to-needs ratio (η2 = 0.003-0.007). Conclusions and Relevance: The findings of this cross-sectional study suggest that different SES indicators have distinct associations with children's brain structure. A high income-to-needs ratio may play a protective role in the context of neighborhood disadvantage and low parent or caregiver educational attainment. This study highlights the importance of considering the joint associations of different SES indicators in future work.

The role of educational attainment and brain morphology in major depressive disorder: Findings from the ENIGMA major depressive disorder consortium.

Brain structural abnormalities and low educational attainment are consistently associated with major depressive disorder (MDD), yet there has been little research investigating the complex interaction of these factors. Brain structural alterations may represent a vulnerability or differential susceptibility marker, and in the context of low educational attainment, predict MDD. We tested this moderation model in a large multisite sample of 1958 adults with MDD and 2921 controls (aged 18 to 86) from the ENIGMA MDD working group. Using generalized linear mixed models and within-sample split-half replication, we tested whether brain structure interacted with educational attainment to predict MDD status. Analyses revealed that cortical thickness in a number of occipital, parietal, and frontal regions significantly interacted with education to predict MDD. For the majority of regions, models suggested a differential susceptibility effect, whereby thicker cortex was more likely to predict MDD in individuals with low educational attainment, but less likely to predict MDD in individuals with high educational attainment. Findings suggest that greater thickness of brain regions subserving visuomotor and social-cognitive functions confers susceptibility to MDD, dependent on level of educational attainment. Longitudinal work, however, is ultimately needed to establish whether cortical thickness represents a preexisting susceptibility marker. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A practical guide for researchers and reviewers using the ABCD Study and other large longitudinal datasets.

As the largest longitudinal study of adolescent brain development and behavior to date, the Adolescent Brain Cognitive Development (ABCD) Study® has provided immense opportunities for researchers across disciplines since its first data release in 2018. The size and scope of the study also present a number of hurdles, which range from becoming familiar with the study design and data structure to employing rigorous and reproducible analyses. The current paper is intended as a guide for researchers and reviewers working with ABCD data, highlighting the features of the data (and the strengths and limitations therein) as well as relevant analytical and methodological considerations. Additionally, we explore justice, equity, diversity, and inclusion efforts as they pertain to the ABCD Study and other large-scale datasets. In doing so, we hope to increase both accessibility of the ABCD Study and transparency within the field of developmental cognitive neuroscience.

Harsh and Inconsistent Parental Discipline Is Associated With Altered Cortical Development in Children.

BACKGROUND: A growing body of evidence suggests that parenting behaviors may affect child mental health via altering brain development. There is a scarcity of research, however, that has investigated associations between parenting behavior and brain structure using longitudinal magnetic resonance imaging. This study aimed to investigate associations between parenting behaviors and structural brain development across the transition from childhood to adolescence. METHODS: Participants were 246 children who provided 436 magnetic resonance imaging datasets covering the age range from 8 to 13 years. Parents (94% mothers) completed self-report measures of parenting behavior, and both children and parents reported on child mental health. Factor analysis was used to identify dimensions of parental behavior. Linear mixed-effects models investigated associations between parenting behaviors and age-related change in cortical thickness and surface area and subcortical volume. Mediation models tested whether brain changes mediated associations between parenting behaviors and changes in internalizing/externalizing symptoms. RESULTS: Hypothesized associations between parenting and amygdala, hippocampal, and frontal trajectories were not supported. Rather, higher levels of parent harsh/inconsistent discipline were associated with decreases in surface area in medial parietal and temporal pole regions and reduced cortical thinning in medial parietal regions. Some effects were present in female but not male children. There were no associations between these neurodevelopmental alterations and symptoms. CONCLUSIONS: This study provides insight into the links between parenting behavior and child neurodevelopment. Given the functions of implicated regions, findings may suggest that parental harsh/inconsistent discipline affects the development of neural circuits subserving sensorimotor and social functioning in children.

Socioeconomic status and the developing brain - A systematic review of neuroimaging findings in youth.

A growing literature has shown associations between socioeconomic disadvantage and neural properties (such as brain structure and function). In this review, we aimed to synthesize findings on the neural correlates of socioeconomic status (SES) in youth samples across neuroimaging modalities. We also aimed to disentangle the effects of different SES measures (e.g., parent income and education) in our synthesis. We found relatively consistent patterns of positive associations between SES and both volume and cortical surface area of frontal regions, and amygdala, hippocampal, and striatal volume (with most consistent results for composite SES indices). Despite limited longitudinal work, results suggest that SES is associated with developmental trajectories of gray matter structure. Higher SES was also found to be associated with increased fractional anisotropy of some white matter tracts, although there were more null than positive findings. Finally, methodological heterogeneity in brain function and connectivity studies prevented us from making strong inferences. Based on our findings, we make recommendations for future research, discuss the role of mitigating factors, and implications for policy.

Similar but distinct - Effects of different socioeconomic indicators on resting state functional connectivity: Findings from the Adolescent Brain Cognitive Development (ABCD) Study®.

Early socioeconomic status (SES) has consistently been associated with child health and cognitive outcomes, in addition to alterations in brain function and connectivity. The goal of the present study was to probe the effects of different facets of SES (parent education, income, and neighborhood disadvantage), that likely represent varying aspects of the environment, on resting state functional connectivity (rsFC). We investigated this question in a large sample of 9475 children (aged 9-10 years) from the Adolescent Brain Cognitive Development (ABCD) Study. Specifically, we analyzed the association between household SES (parent education, income-to-needs ratio) and neighborhood disadvantage, and system-level rsFC using within-sample split-half replication. We then tested whether the associations were unique to each SES measure, and whether household SES and neighborhood disadvantage had interactive effects on rsFC. SES measures had both common and distinct effects on rsFC, with sensory-motor systems (e.g., sensorimotor network) and cognitive networks (e.g., front-parietal network) particularly implicated. Further, the association between neighborhood disadvantage and sensorimotor network connectivity was less pronounced in the presence of high income-to-needs. Findings demonstrate that different facets of SES have distinct and interacting effects on rsFC, highlighting the importance of considering different indicators when studying the effects of SES on the brain.

Neighborhood disadvantage and longitudinal brain-predicted-age trajectory during adolescence.

Neighborhood disadvantage has consistently been linked to alterations in brain structure; however, positive environmental (e.g., positive parenting) and psychological factors (e.g., temperament) may buffer these effects. We aimed to investigate associations between neighborhood disadvantage and deviations from typical neurodevelopmental trajectories during adolescence, and examine the moderating role of positive parenting and temperamental effortful control (EC). Using a large dataset (n = 1313), a normative model of brain morphology was established, which was then used to predict the age of youth from a longitudinal dataset (n = 166, three time-points at age 12, 16, and 19). Using linear mixed models, we investigated whether trajectories of the difference between brain-predicted-age and chronological age (brainAGE) were associated with neighborhood disadvantage, and whether positive parenting (positive behavior during a problem-solving task) and EC moderated these associations. We found that neighborhood disadvantage was associated with positive brainAGE during early adolescence and a deceleration (decreasing brainAGE) thereafter. EC moderated this association such that in disadvantaged adolescents, low EC was associated with delayed development (negative brainAGE) during late adolescence. Findings provide evidence for complex associations between environmental and psychological factors, and brain maturation. They suggest that neighborhood disadvantage may have long-term effects on neurodevelopment during adolescence, but high EC could buffer these effects.