Parent Psychopathology and Behavioral Effects on Child Brain-Symptom Networks in the ABCD Study.

OBJECTIVE: Parents play a notable role in the development of child psychopathology. In this study, we investigated the role of parent psychopathology and behaviors on child brain-symptom networks to understand the role of intergenerational transmission of psychopathology. Few studies have documented the interaction of child psychopathology, parent psychopathology, and child neuroimaging. METHOD: We used the baseline cohort of the Adolescent Brain Cognitive Development Study (N = 7,151, female-at-birth = 3,619, aged 9-11 years) to derive brain-symptom networks using sparse canonical correlation analysis with the Child Behavior Checklist and resting-state functional magnetic resonance imaging. We then correlated parent psychopathology symptoms and parental behaviors with child brain-symptom networks. Finally, we used the significant correlations to understand, using the mediation R package, whether parent behaviors mediated the effect of parent psychopathology on child brain connectivity. RESULTS: We observed 3 brain-symptom networks correlated with externalizing (r = 0.19, internalizing (r = 0.17), and neurodevelopmental symptoms (r = 0.18). These corresponded to differences in connectivity between the default mode-default mode, default mode-control, and visual-visual canonical networks. We further detected aspects of parental psychopathology, including personal strength, thought problems, and rule-breaking symptoms to be associated with child brain connectivity. Finally, we found that parental behaviors and symptoms mediate each other's relationship to child brain connectivity. CONCLUSION: The current study suggests that positive parental behaviors can relieve potentially detrimental effects of parental psychopathology, and vice versa, on symptom-correlated child brain connectivity. Altogether, these results provide a framework for future research and potential targets for parents who experience mental health symptoms to help mitigate potential intergenerational transmission of mental illness.

The promise of compassion-based therapy as a novel intervention for adolescent PTSD.

In this review, we summarize current evidence for compassion-based approaches for PTSD and the potential for their application to the adolescent PTSD population. Exposure to traumatic events is common in adolescence and PTSD remains a public health crisis. Accessibility, willingness, and engagement are significant barriers to established treatments for PTSD, with attrition rates as high as 50 %. Compassion-based therapies provide potential solutions to treatment obstacles by providing a non-threatening, transdiagnostic option unburdened by aspects of current trauma treatment which may be associated with treatment resistance (e.g., exposure, trauma narrative, induction of fear). Compassion-based approaches are intuitive for trauma treatment, as compassion activates the self-soothing system, thereby disarming the fear system and promoting affect regulation. Compassion-based treatments demonstrate reductions across a substantial range of PTSD symptoms in adults, however, in adolescents extant literature is sparse, with cross-sectional studies suggesting self-compassion is inversely associated with trauma-related psychopathology. Understanding the impact of compassion-based approaches on adolescent PTSD is warranted as the adolescent developmental period may be a particularly opportune time for this approach. Evaluation of the impact of compassion-based treatment on adolescent PTSD in clinical populations via randomized-controlled studies and comparison of its relative efficacy to current evidence-based practices is warranted.

Differential Cortical Volume and Surface Morphometry in Youth With Chronic Health Conditions.

Up to 1 in 3 youth in the United States have a childhood-onset chronic health condition (CHC), which can lead to neurodevelopmental disruptions in cognitive functioning and brain structure. However, the nature and extent of structural neurobiomarkers that may be consistent across a broad spectrum of CHCs are unknown. Thus, the purpose of this study was to identify potential differences in brain structure in youth with and without chronic physical health conditions (e.g., diabetes, hemophilia). Here, 49 T1 structural magnetic resonance imaging (MRI) images were obtained from youth with (n = 26) and without (n = 23) CHCs. Images were preprocessed using voxel-based morphometry (VBM) to generate whole-brain voxel-wise gray matter volume maps and whole-brain extracted estimates of cortical surface area and cortical thickness. Multi-scanner harmonization was implemented on surface-based estimates and linear models were used to estimate significant main effects of the group. We detected widespread decreases in brain structure in youth with CHCs as compared to controls in regions of the prefrontal, cingulate, and visual association areas. The insula exhibited the opposite effect, with cases having increased surface area as compared to controls. To our knowledge, these findings identify a novel structural biomarker of childhood-onset CHCs, with consistent alterations identified in gray matter of regions in the prefrontal cortex and insula involved in emotion regulation and executive function. These findings, while exploratory, may reflect an impact of chronic health stress in the adolescent brain, and suggest that more comprehensive assessment of stress and neurodevelopment in youth with CHCs may be appropriate.

A systematic review of childhood maltreatment and resting state functional connectivity.

Resting-state functional connectivity (rsFC) has the potential to shed light on how childhood abuse and neglect relates to negative psychiatric outcomes. However, a comprehensive review of the impact of childhood maltreatment on the brain's resting state functional organization has not yet been undertaken. We systematically searched rsFC studies in children and youth exposed to maltreatment. Nineteen studies (total n = 3079) met our inclusion criteria. Two consistent findings were observed. Childhood maltreatment was linked to reduced connectivity between the anterior insula and dorsal anterior cingulate cortex, and with widespread heightened amygdala connectivity with key structures in the salience, default mode, and prefrontal regulatory networks. Other brain regions showing altered connectivity included the ventral anterior cingulate cortex, dorsolateral prefrontal cortex, and hippocampus. These patterns of altered functional connectivity associated with maltreatment exposure were independent of symptoms, yet comparable to those seen in individuals with overt clinical disorder. Summative findings indicate that rsFC alterations associated with maltreatment experience are related to poor cognitive and social functioning and are prognostic of future symptoms. In conclusion, maltreatment is associated with altered rsFC in emotional reactivity, regulation, learning, and salience detection brain circuits. This indicates patterns of recalibration of putative mechanisms implicated in maladaptive developmental outcomes.

Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium.

BACKGROUND: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. METHODS: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. RESULTS: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. CONCLUSION: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.

A proof-of-concept study of vicarious extinction learning and autonomic synchrony in parent-child dyads and posttraumatic stress disorder.

Though threat-extinction models continue to inform scientific study of traumatic stress, knowledge of learning and extinction as mechanisms linking exposure to psychopathology remains critically limited among youth. This proof-of-concept study advances the study of threat-extinction in youth by determining feasibility of electrodermal stimulation (EDS), vicarious extinction learning via their parent, and social threat learning in pediatric PTSD (pPTSD). Typically developing (TD) and PTSD-diagnosed youth in 45 mother-child dyads completed an extinction learning paradigm. The use of EDS was first investigated in a cohort of TD youth (n = 20) using a 2-day paradigm without vicarious extinction, while direct (for TD and pPTSD) and vicarious (for pPTSD) extinction were investigated in a 3-day paradigm (n = 25). Threat acquisition and extinction were monitored using skin-conductance response (SCR) and behavioral expectations of EDS. Using Bayesian modeling to accommodate this pilot sample, our results demonstrate: (1) EDS-conditioning to be highly feasible and well-tolerated across TD and trauma-exposed youth, (2) Successful direct and vicarious extinction learning in trauma-exposed youth, and (3) PTSD-associated patterns in extinction learning and physiological synchrony between parent-child dyads. In summary, these novel approaches have the potential to advance translational studies in the mechanistic understanding of parent-child transmission of risk and youth psychopathology.

Neurogenetic mechanisms of risk for ADHD: Examining associations of polygenic scores and brain volumes in a population cohort.

BACKGROUND: ADHD polygenic scores (PGSs) have been previously shown to predict ADHD outcomes in several studies. However, ADHD PGSs are typically correlated with ADHD but not necessarily reflective of causal mechanisms. More research is needed to elucidate the neurobiological mechanisms underlying ADHD. We leveraged functional annotation information into an ADHD PGS to (1) improve the prediction performance over a non-annotated ADHD PGS and (2) test whether volumetric variation in brain regions putatively associated with ADHD mediate the association between PGSs and ADHD outcomes. METHODS: Data were from the Philadelphia Neurodevelopmental Cohort (N = 555). Multiple mediation models were tested to examine the indirect effects of two ADHD PGSs-one using a traditional computation involving clumping and thresholding and another using a functionally annotated approach (i.e., AnnoPred)-on ADHD inattention (IA) and hyperactivity-impulsivity (HI) symptoms, via gray matter volumes in the cingulate gyrus, angular gyrus, caudate, dorsolateral prefrontal cortex (DLPFC), and inferior temporal lobe. RESULTS: A direct effect was detected between the AnnoPred ADHD PGS and IA symptoms in adolescents. No indirect effects via brain volumes were detected for either IA or HI symptoms. However, both ADHD PGSs were negatively associated with the DLPFC. CONCLUSIONS: The AnnoPred ADHD PGS was a more developmentally specific predictor of adolescent IA symptoms compared to the traditional ADHD PGS. However, brain volumes did not mediate the effects of either a traditional or AnnoPred ADHD PGS on ADHD symptoms, suggesting that we may still be underpowered in clarifying brain-based biomarkers for ADHD using genetic measures.

Editorial: White Matter and Youth Psychopathology: Case Closed?

Psychiatric problems in children (and adults) are reflected in brain networks. Remarkable advances in functional magnetic resonance imaging continue to evince a bidirectional relation between the functional flow of activation across the brain and the etiology of psychiatric disorders. This work is analogous to that of a city engineer surveying traffic to understand flow patterns, efficiency, congestion, and even the influence of city-wide conditions (eg, snowfall). Yet, the engineer further considers a factor long neglected in human neuroscience-the roads. Functional connectivity does not take place across the intercellular ether, but across a nexus of millions of interconnected axonal pathways or white matter (WM), so named for the color given by the fatty myelin surrounding the axons. Insight into the role of these tracts in the pathology of psychiatric illness continues to be limited, in contrast to the functional connectivity they support. WM tracts are among the last components of the brain to reach maturity, and their malleability in youth may play a key role in the manifestation of psychopathology in children. An emerging body of research suggests that pediatric psychopathology may be caused in part by WM alterations at both the global and the regional levels.1 Yet, these findings are almost exclusively derived from cross-sectional studies, which cannot model developmental course, and small sample sizes, which limit the ability to draw firm conclusions.

Consensus design of a calibration experiment for human fear conditioning.

Fear conditioning is a widely used laboratory model to investigate learning, memory, and psychopathology across species. The quantification of learning in this paradigm is heterogeneous in humans and psychometric properties of different quantification methods can be difficult to establish. To overcome this obstacle, calibration is a standard metrological procedure in which well-defined values of a latent variable are generated in an established experimental paradigm. These intended values then serve as validity criterion to rank methods. Here, we develop a calibration protocol for human fear conditioning. Based on a literature review, series of workshops, and survey of N = 96 experts, we propose a calibration experiment and settings for 25 design variables to calibrate the measurement of fear conditioning. Design variables were chosen to be as theory-free as possible and allow wide applicability in different experimental contexts. Besides establishing a specific calibration procedure, the general calibration process we outline may serve as a blueprint for calibration efforts in other subfields of behavioral neuroscience that need measurement refinement.

Sex-based variations of prefrontal structure and longitudinal symptoms in pediatric posttraumatic stress disorder.

BACKGROUND: Pediatric posttraumatic stress disorder (pPTSD) is more than three times as likely to develop in trauma-exposed female youth than males. Despite the staggering sex differences in the prevalence rates of pPTSD and symptom expression, relatively little is known about the underlying biomarkers of these sex-based variations in pPTSD as compared to typically development. METHODS: The Youth PTSD study recruited 97 youth, ages of 7 and 18, to undergo comprehensive clinical assessments and T1-weighted MRI to evaluate the extent to which sex can explain PTSD-related variations in brain structure. Whole-brain VBM as well as whole-brain estimates of cortical thickness and surface area were analyzed to identify group-by-sex interactions. Finally, we tested whether current or future symptom severity was predictive of regions exhibiting sex-based variations. RESULTS: Clinically, females with PTSD were significantly more likely to report exposure to and higher severity of interpersonal violence and symptoms of hyperarousal. Sex and PTSD status were predictive of gray matter across the lateral prefrontal cortex (PFC), including the ventrolateral PFC and frontal pole, where increased volume and surface area was found in PTSD females as compared to PTSD males. Interestingly, the ventrolateral prefrontal cortex and frontal pole were negatively predictive of symptoms 1 year later in only males with PTSD. CONCLUSIONS: Together, these results establish that youth with PTSD exhibit sex-based variations in clinical and trauma characteristics and prefrontal cortical structure relative to normative development. This work demonstrates the importance of examining the role that sex may play in the behavioral and neurobiological presentation of pPTSD.

The impact of childhood maltreatment on adaptive emotion regulation strategies.

OBJECTIVE: Childhood maltreatment is a potent known risk factor for psychopathology, accounting for nearly 30% of the risk for mental illness in adulthood. One mechanism by which maltreatment contributes to psychopathology is through impairments in emotion regulation. However, the impact of childhood maltreatment on adaptive regulation strategies remains unclear, particularly across positive and negative emotions. METHODS: Using Mechanical Turk, we recruited a cross-sectional sample of 207 adults (21-69 years) with and without childhood maltreatment exposure to complete an emotion regulation task where they were shown positive and negative emotional pictures and were instructed to reappraise or accept their emotions, alongside a non-instruction comparison condition. Participants rated their emotional intensity following each image, as well as perceived effectiveness of each strategy at the end of each block. We first investigated the impact of image valence and strategy use on the intensity of post-image emotions, followed by interacting both maltreatment exposure and severity with valence and strategy. FINDINGS: Surprisingly, maltreated individuals showed significantly higher emotional intensity compared to non-maltreated individuals, specifically toward positive images (F(2,194.6) = 5.01, p < 0.01). When examining strategy, the use of acceptance to regulate negative emotions was equally effective across all levels of maltreatment severity (F(2,194.6) = 15.93, p < 0.001), while reappraisal was effective only at lower maltreatment levels. CONCLUSION: These findings suggest that experiences of childhood maltreatment exert differential impacts on the ability to regulate positive and negative emotions using key adaptive regulation strategies, which has implications for both psychopathology risk and treatment interventions.

Longitudinal hippocampal circuit change differentiates persistence and remission of pediatric posttraumatic stress disorder.

BACKGROUND: Previous studies have identified functional brain abnormalities in pediatric posttraumatic stress disorder (pPTSD) suggesting altered frontoparietal-subcortical function during emotion processing. However, little is known about how the brain functionally changes over time in recovery versus the persistence of pPTSD. METHODS: This longitudinal study recruited 23 youth with PTSD and 28 typically developing (TD) youth (ages: 8.07-17.99). Within the PTSD group, nine remitted by the 1-year follow-up (Remit) while the remaining 14 persisted (PTSD). At each visit, youth completed an emotional processing task in which they viewed threat and neutral images during functional magnetic resonance imaging (fMRI). Voxelwise activation analyses using linear mixed-effects regression were conducted using a group (TD, Remit, PTSD) by time (baseline, follow-up) by valence (threat, neutral) design. Based on activation findings, a subsequent analysis of hippocampal functional connectivity was performed using a similar model. RESULTS: PTSD youth showed significantly increasing hippocampal activation to threatening images compared to TD youth, while the Remit group showed more similar patterns to TD youth. Subsequent hippocampal functional connectivity analyses reveal the Remit group showed increasing functional connectivity between the hippocampus and visual cortex (V4) while viewing threat stimuli. CONCLUSIONS: These findings represent one of the first preliminary reports of functional brain substrates of persistence and remission in pPTSD. Notably, increased hippocampal activation to threat and decreased connectivity in the hippocampal-V4 network over time may contribute to persistence in pPTSD. These findings suggest potential biomarkers that could be utilized to advance the treatment of pediatric PTSD.

Childhood exposure to interpersonal violence is associated with greater transdiagnostic integration of psychiatric symptoms.

BACKGROUND: Childhood exposure to interpersonal violence (IPV) may be linked to distinct manifestations of mental illness, yet the nature of this change remains poorly understood. Network analysis can provide unique insights by contrasting the interrelatedness of symptoms underlying psychopathology across exposed and non-exposed youth, with potential clinical implications for a treatment-resistant population. We anticipated marked differences in symptom associations among IPV-exposed youth, particularly in terms of 'hub' symptoms holding outsized influence over the network, as well as formation and influence of communities of highly interconnected symptoms. METHODS: Participants from a population-representative sample of youth (n = 4433; ages 11-18 years) completed a comprehensive structured clinical interview assessing mental health symptoms, diagnostic status, and history of violence exposure. Network analytic methods were used to model the pattern of associations between symptoms, quantify differences across diagnosed youth with (IPV+) and without (IPV-) IPV exposure, and identify transdiagnostic 'bridge' symptoms linking multiple disorders. RESULTS: Symptoms organized into six 'disorder' communities (e.g. Intrusive Thoughts/Sensations, Depression, Anxiety), that exhibited considerably greater interconnectivity in IPV+ youth. Five symptoms emerged in IPV+ youth as highly trafficked 'bridges' between symptom communities (11 in IPV- youth). CONCLUSION: IPV exposure may alter mutually reinforcing symptom co-occurrence in youth, thus contributing to greater psychiatric comorbidity and treatment resistance. The presence of a condensed and unique set of bridge symptoms suggests trauma-enriched nodes which could be therapeutically targeted to improve outcomes in violence-exposed youth.

Neurobehavioral correlates of impaired emotion recognition in pediatric PTSD.

Despite broad evidence suggesting that adversity-exposed youth experience an impaired ability to recognize emotion in others, the underlying biological mechanisms remains elusive. This study uses a multimethod approach to target the neurological substrates of this phenomenon in a well-phenotyped sample of youth meeting diagnostic criteria for posttraumatic stress disorder (PTSD). Twenty-one PTSD-afflicted youth and 23 typically developing (TD) controls completed clinical interview schedules, an emotion recognition task with eye-tracking, and an implicit emotion processing task during functional magnetic resonance imaging )fMRI). PTSD was associated with decreased accuracy in identification of angry, disgust, and neutral faces as compared to TD youth. Of note, these impairments occurred despite the normal deployment of visual attention in youth with PTSD relative to TD youth. Correlation with a related fMRI task revealed a group by accuracy interaction for amygdala-hippocampus functional connectivity (FC) for angry expressions, where TD youth showed a positive relationship between anger accuracy and amygdala-hippocampus FC; this relationship was reversed in youth with PTSD. These findings are a novel characterization of impaired threat recognition within a well-phenotyped population of severe pediatric PTSD. Further, the differential amygdala-hippocampus FC identified in youth with PTSD may imply aberrant efficiency of emotional contextualization circuits.

Differential Patterns of Delayed Emotion Circuit Maturation in Abused Girls With and Without Internalizing Psychopathology.

OBJECTIVE: Childhood abuse represents one of the most potent risk factors for developing psychopathology, especially in females. Evidence suggests that exposure to early-life adversity may be related to advanced maturation of emotion processing neural circuits. However, it remains unknown whether abuse is related to early circuit maturation and whether maturation patterns depend on the presence of psychopathology. METHODS: A multisite sample of 234 girls (ages 8-18 years) completed clinical assessment, maltreatment histories, and high-resolution T1-weighted structural MRI. Girls were stratified by abuse history and internalizing disorder diagnosis into typically developing (no abuse/no diagnosis), resilient (abuse/no diagnosis), and susceptible (abuse/current diagnosis) groups. Machine learning models of normative brain development were aggregated in a stacked generalization framework trained to predict chronological age using gray matter volume in whole-brain, emotion, and language circuit parcellations. Brain age gap estimations (BrainAGEs; predicted age minus true chronological age) were calculated as indices of relative circuit maturation. RESULTS: Childhood abuse was related to reduced BrainAGE (delayed maturation) specific to emotion circuits. Delayed emotion circuit BrainAGE was further related to increased hyperarousal symptoms. Childhood physical neglect was associated with increased whole-brain BrainAGE (advanced maturation). Neural contributors to emotion circuit BrainAGE differed in girls with and without an internalizing diagnosis, especially in the lateral prefrontal, parietal, and insular cortices and the hippocampus. CONCLUSIONS: Abuse exposure in girls is associated with a delayed structural maturation pattern specific to emotion circuitry, a potentially adaptive mechanism enhancing threat generalization. Physical neglect, on the other hand, is associated with a broader brain-wide pattern of advanced structural maturation. The differential influence of fronto-parietal cortices and the hippocampus on emotion circuit maturity in resilient girls may represent neurodevelopmental markers of reduced psychiatric risk following abuse.

Pediatric PTSD is characterized by age- and sex-related abnormalities in structural connectivity.

Pediatric post-traumatic stress disorder (pPTSD) is a prevalent and pervasive form of mental illness comprising a disparate constellation of psychiatric symptoms. Emerging evidence suggests that pPTSD may be characterized by alterations in functional networks traversing the brain. Yet, little is known about pathological changes in the structural tracts underlying functional connectivity. In adults, PTSD is linked to widespread change in white matter integrity throughout the brain, yet similar studies with youth populations have yet to be conducted. Current understanding of the nature and treatment of pPTSD may be enhanced by examining alterations in white matter, while further untangling effects of age and sex. Here, we assess the microstructure of 12 major white matter tracts in a sample of well-phenotyped youth with PTSD. Measures of fractional anisotropy were derived from diffusion tensor images acquired from 82 unmediated youth (ages 8-18), of whom 39 met criteria for pPTSD. Diagnosis of pPTSD was linked to remarkable age- and sex-linked differences in the microstructure of major white matter tracts including the uncinate fasciculus, cingulum bundle, and inferior longitudinal fasciculus. In each case, youth with PTSD show an absence of increased white matter integrity with age, suggesting an altered pattern of neurodevelopment that may contribute to persistence or worsening of illness. Broadly, our results suggest abnormal white matter development in pediatric PTSD, a finding which may contribute to illness persistence, comorbidity with other disorders, and poorer prognosis across time. Critically, these findings further speak to the nature of pPTSD as a 'whole-brain' disorder.

Differential DNA Methylation Is Associated With Hippocampal Abnormalities in Pediatric Posttraumatic Stress Disorder.

BACKGROUND: Recent findings in neuroimaging and epigenetics offer important insights into brain structures and biological pathways of altered gene expression associated with posttraumatic stress disorder (PTSD). However, it is unknown to what extent epigenetic mechanisms are associated with PTSD and its neurobiology in youth. METHODS: In this study, we combined a methylome-wide association study and structural neuroimaging measures in a Dutch cohort of youths with PTSD (8-18 years of age). We aimed to replicate findings in a similar independent U.S. cohort. RESULTS: We found significant methylome-wide associations for pediatric PTSD (false discovery rate p < .05) compared with non-PTSD control groups (traumatized and nontraumatized youths). Methylation differences on nine genes were replicated, including genes related to glucocorticoid functioning. In both cohorts, methylation on OLFM3 gene was further associated with anterior hippocampal volume. CONCLUSIONS: These findings point to molecular pathways involved in inflammation, stress response, and neuroplasticity as potential contributors to neural abnormalities and provide potentially unique biomarkers and treatment targets for pediatric PTSD.

Translating the neuroscience of adverse childhood experiences to inform policy and foster population-level resilience.

Imaging methods have elucidated several neurobiological correlates of traumatic and adverse experiences in childhood. This knowledge base may foster the development of programs and policies that aim to build resilience and adaptation in children and youth facing adversity. Translation of this research requires both effective and accurate communication of the science. This review begins with a discussion of integrating the language used to describe and identify childhood adversity and their outcomes to clarify the translation of neurodevelopmental findings. An integrative term, Traumatic and Adverse Childhood Experiences (TRACEs+) is proposed, alongside a revised adverse childhood experiences (ACEs) pyramid that emphasizes that a diversity of adverse experiences may lead to a common outcome and that a diversity of outcomes may result from a common adverse experience. This term facilitates linkages between the ACEs literature and the emerging neurodevelopmental knowledge surrounding the effect of traumatic adverse childhood experiences on youth in terms of the knowns and unknowns about neural connectivity in youth samples. How neuroscience findings may lead directly or indirectly to specific techniques or targets for intervention and the reciprocal nature of these relationships is addressed. Potential implications of the neuroscience for policy and intervention at multiple levels are illustrated using existing policy programs that may be informed by (and inform) neuroscience. The need for transdisciplinary models to continue to move the science to action closes the article. (PsycInfo Database Record (c) 2021 APA, all rights reserved).