cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.15154/1524640
title: Evaluation of Attention-Deficit/Hyperactivity Disorder Medications, Externalizing Symptoms, and Suicidality in Children

description: IMPORTANCE: Childhood suicidality (ie, suicidal ideation or attempts) rates are increasing. Attention-deficit/hyperactivity disorder (ADHD) and externalizing symptoms are common risk factors associated with suicidality. More data are needed to describe associations of ADHD pharmacotherapy with childhood suicidality.

OBJECTIVE: To investigate whether ADHD pharmacotherapy is associated with externalizing symptoms and childhood suicidality.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, cross-sectional and 1-year-longitudinal associations were examined using data (collected during 2016-2019) from the Adolescent Brain Cognitive Development (ABCD) Study, a large, diverse US sample of children aged 9 to 11 years. Data analysis was performed from November to December 2020.

EXPOSURES: Main and interaction associations of externalizing symptoms (hyperactivity ADHD symptoms, oppositional defiant, and conduct disorder symptoms) and ADHD medication treatment (methylphenidate and amphetamine derivatives, α-2-agonists, and atomoxetine) at baseline assessment.

MAIN OUTCOMES AND MEASURES: Child-reported suicidality (past and present at baseline; current at longitudinal assessment). Covariates were age, sex, race/ethnicity, parents’ education, marital status, and concomitant child psychiatric pharmacotherapy (antidepressants and antipsychotics).

RESULTS: Among 11878 children at baseline assessment (mean [SD] age, 9.9 [0.6] years; 6196 boys [52.2%]; 8805 White [74.1%]), 1006 (8.5%) were treated with ADHD medication and 1040 (8.8%) reported past or current suicidality. Externalizing symptoms (median [range], 1 [0-29] symptom count) were associated with suicidality (for a change of 1 SD in symptoms, odds ratio [OR], 1.34; 95% CI, 1.26-1.42; P < .001), as was ADHD medication treatment (OR, 1.32; 95% CI, 1.06-1.64; P = .01). ADHD medication use was associated with less suicidality in children with more externalizing symptoms (significant symptom-by-medication interaction, B = −0.250; SE = 0.086; P = .004), such that for children who were not receiving ADHD medications, there was an association between more externalizing symptoms and suicidality (for a change of 1 SD in symptoms, OR, 1.42; 95% CI, 1.33-1.52; P < .001); however, for children who were receiving ADHD medication, there was no such association (OR, 1.15; 95% CI, 0.97-1.35; P = .10). The association with medication remained even when covarying for multiple confounders, including risk and protective factors for suicidality in ABCD, and was replicated in 1-year longitudinal follow-up. Sensitivity analyses matching participants with high numbers of externalizing symptoms taking and not taking ADHD medication treatment confirmed its association with less suicidality.

CONCLUSIONS AND RELEVANCE: These findings suggest that ADHD medication treatment is associated with less suicidality in children with substantial externalizing symptoms and may be used to inform childhood suicide prevention strategies.
DOI: 10.15154/1524641
title: Contributions of PTSD polygenic risk and environmental stress to suicidality in preadolescents

description: Suicidal ideation and attempts (i.e., suicidality) are complex behaviors driven by environmental stress, genetic susceptibility, and their interaction. Preadolescent suicidality is a major health problem with rising rates, yet its underlying biology is understudied. Here we studied effects of genetic stress susceptibility, approximated by the polygenic risk score (PRS) for post-traumatic-stress-disorder (PTSD), on preadolescent suicidality in participants from the Adolescent Brain Cognitive Development (ABCD) Study®. We further evaluated PTSD-PRS effects on suicidality in the presence of environmental stressors that are established suicide risk factors. Analyses included both European and African ancestry participants using PRS calculated based on summary statistics from ancestry- specific genome-wide association studies. In European ancestry participants (N = 4,619, n = 378 suicidal), PTSD- PRS was associated with preadolescent suicidality (odds ratio [OR] = 1.12, 95%CI 1–1.25, p = 0.038). Results in African ancestry participants (N = 1,334, n = 130 suicidal) showed a similar direction but were not statistically significant (OR = 1.21, 95%CI 0.93–1.57, p = 0.153). Sensitivity analyses using non-psychiatric polygenic score for height and using cross-ancestry PTSD-PRS did not reveal any association with suicidality, supporting the specificity of the association of ancestry-specific PTSD-PRS with suicidality. Environmental stressors were robustly associated with suicidality across ancestries with moderate effect size for negative life events and family conflict (OR 1.27–1.6); and with large effect size (OR ~ 4) for sexual-orientation discrimination. When combined with environmental factors, PTSD-PRS showed marginal additive effects in explaining variability in suicidality, with no evidence for G × E interaction. Results support use of cross-phenotype PRS, specifically stress- susceptibility, as a genetic marker for suicidality risk early in the lifespan.
DOI: 10.15154/1524646
title: The Relation between Parent Mental Health and Child Internalizing Symptoms in Parent Child Interaction Therapy

description: The present study evaluated whether families receiving Parent Child Interaction Therapy (PCIT) experienced significant improvements in both parent and child internalizing symptoms, and if so, whether the relationship between improvement in child externalizing symptoms and internalizing symptoms was mediated by reductions in parenting stress and parent depressive symptoms. Participants were an ethnically diverse sample of 72 families with 2-7 year old children experiencing clinically significant externalizing symptoms who were assigned to receive a version of PCIT in one of two previously conducted clinical trials designed to evaluate culturally modified PCIT. Analyses revealed that parent-reported child internalizing symptoms, parenting stress, and parent depressive symptoms improved significantly from pre to post treatment in PCIT. Additionally, the relation between child externalizing improvement and internalizing improvement was mediated through reduction in parenting stress, but not parent depressive symptoms. These findings suggest that ethnically diverse children are likely to experience significant improvement in co-occurring externalizing and internalizing symptoms following PCIT. Furthermore, decreases in parenting stress may play a role in the improvement of child internalizing symptoms.
DOI: 10.15154/1524665
title: Characterizing the Neural Correlates of Response Inhibition and Error Processing in Children with Symptoms of Irritability and/or Attention-Deficit/Hyperactivity Disorder in the ABCD Study® 

description: Attention-deficit/hyperactivity disorder (ADHD), characterized by symptoms of inattention and/or hyperactivity and impulsivity, is a neurodevelopmental disorder associated with executive dysfunctions, including response inhibition and error processing. Research has documented a common co-occurrence between ADHD and pediatric irritability. The latter is more characterized by affective symptoms, specifically frequent temper outbursts and low frustration tolerance relative to typically developing peers. Shared and nonshared neural correlates of youths with varied profiles of ADHD and irritability symptoms during childhood remain largely unknown. This study first classified a large sample of youths in the Adolescent Brain Cognitive Development (ABCD) study at baseline into distinct phenotypic groups based on ADHD and irritability symptoms (N=11,748), and then examined shared and nonshared neural correlates of response inhibition and error processing during the Stop Signal Task in a subset of sample with quality neuroimaging data (N=5,948). Latent class analysis (LCA) revealed four phenotypic groups, i.e., high ADHD with co-occurring irritability symptoms (n=787, 6.7%), moderate ADHD with low irritability symptoms (n=901, 7.7%), high irritability with no ADHD symptoms (n=279, 2.4%), and typically developing peers with low ADHD and low irritability symptoms (n=9,781, 83.3%). Latent variable modeling revealed group differences in the neural coactivation network supporting response inhibition in the fronto-parietal regions, but limited differences in error processing across frontal and posterior regions. These neural differences were marked by decreased coactivation in the irritability only group relative to youths with ADHD and co-occurring irritability symptoms and typically developing peers during response inhibition. Together, this study provided initial evidence for differential neural mechanisms of response inhibition associated with ADHD, irritability, and their co-occurrence. Precision medicine attending to individual differences in ADHD and irritability symptoms and the underlying mechanisms are warranted when treating affected children and families.
DOI: 10.15154/1524666
title: Association of Cyber-victimization and Cyber-bullying with Suicidality in Early Adolescence: Findings from the Adolescent Brain Cognitive Development (ABCD) Study

description: Importance: Adolescent suicidality (i.e., suicidal ideation or attempt) is a major health concern. Cyber-victimization and cyber-bullying have become increasingly prevalent and are associated with mental health burden, but their roles as independent suicidality risk factors remain unclear. Data is needed to clarify their unique contribution to teen suicidality to inform suicide prevention efforts.
Objective: To examine whether cyber-victimization and cyber-bullying are distinct stressors divergent from other forms of peer victimization and aggression in their association with suicidality in early adolescence. 
Design, Setting, and Participants: Cross-sectional analysis of data (collected July 2018- January 2021) from the Adolescent Brain Cognitive Development study (ABCD Study®), a large, diverse sample of US children (age 10-13 years). 
Exposure: Experiences of cyber-victimization and cyber-bullying.
Main Outcomes and Measures: Youth-reported suicidality (past/present as reported in the ABCD Study 2-year follow-up assessment). Covariates included demographics, established environmental risk and protective factors for youth suicidality, psychopathology, and offline peer victimization and aggression experiences. 
Results: Among 10 414 ABCD Study participants included in the analysis, 796 endorsed suicidality (7.6%). A total of 930 (8.9%) reported cyber-victimization and 96 (0.9%) reported cyber-bullying, of whom 66 also endorsed cyber-victimization. Controlling for demographics, cyber-victimization was associated with suicidality (odds ratio [OR]=4.2, 95% confidence interval [CI] 3.5-5.1, P<.001), while cyber-bullying was not (OR=1.5, 95%CI 0.8-2.3, P=.3). Cyber-victimization remained associated with suicidality when accounting for negative life events, family conflict, parental monitoring, school environment, and racial/ethnic discrimination (OR=2.5, 95%CI 2-3, P<.001); and when further covarying for internalizing and externalizing psychopathology (OR=1.8, 95%CI 1.4-2.4, P<.001). Both offline (i.e., traditional) peer victimization and peer aggression were associated with suicidality (OR=1.5, 95%CI 1.1-2 for both, controlling for all covariates described above). When including both online cyber-victimization and offline peer experiences, cyber-victimization remained associated with suicidality (OR=1.7, 95%CI 1.3-2.2, P<.001, controlling for all covariates). 
Conclusions and relevance: In this cross-sectional study, cyber-victimization, but not cyber-bullying, was associated with suicidality in early adolescence. The association was significant over and above other suicidality risk factors, including offline victimization/aggression. Findings can inform adolescent suicide prevention strategies and suggest that clinicians and educational staff working with this population routinely evaluate for adolescents’ cyber-victimization.
DOI: 10.15154/1524672
title: Personalizing PCIT for Culturally Diverse Families:  Outcomes From A Pilot Trial Utilizing the PersIn Framework

description: The PersIn framework is a proposed approach for personalizing evidence-based interventions to increase cultural responsiveness. This study describes pilot feasibility outcomes for MY PCIT (n=32), a personalized version of Parent-Child Interaction Therapy for culturally diverse families that was developed as a proof-of-concept of the PersIn framework.  MY PCIT produced both statistically and clinically significant changes in pre-to post-treatment child outcomes and parent outcomes.  Child behavior change outcomes were similar to or better than those reported by three benchmark studies.
DOI: 10.15154/1524711
title: Brain Structure Relations with Psychopathology Trajectories in the Adolescent Brain Cognitive Development Study®

description: Objective: A general psychopathology (‘p’) factor captures shared variation across mental disorders. Structural neural alterations have been associated with p concurrently, but less is known about whether these alterations relate to within-person change in p over time, especially during preadolescence, a period of neurodevelopmental changes.
Methods: We examined whether baseline brain structure was prospectively related to the trajectory of p and specific forms of psychopathology over two years in 9,220 preadolescents (aged 9-10 at baseline) from the Adolescent Brain Cognitive Development Study®. We conducted longitudinal multilevel models to determine whether baseline brain structure (volume, surface area, thickness) was associated with between-person differences and within-person change in p (from a higher-order confirmatory factor model) and internalizing, externalizing,
neurodevelopmental, somatization, and detachment factor scores (from a correlated factors model) over three study waves.
Results: Smaller global volume and surface area, but not thickness, were associated with higher between-person levels of p, which persisted over time. None of the brain structure measures related to within-person change in p. Lower baseline cortical thickness was associated with steeper decreases in internalizing psychopathology, which was driven by lower thickness within sensorimotor and temporal regions.
Conclusions: These novel results identify specific brain structure features that might contribute to transdiagnostic psychopathology development in preadolescence. Children with smaller total brain volume and surface area may be vulnerable to persistent general psychopathology during preadolescence. Cortical thinning reflective of pruning and myelination in sensorimotor and temporal brain regions specifically may protect against increases in internalizing, but not general psychopathology during preadolescence.
DOI: 10.15154/1524739
title: Associations between prenatal exposure to gestational diabetes mellitus, brain structure, and child adiposity markers

description: Objectives: To investigate the mediating role of child brain structure in the relationships between prenatal gestational diabetes mellitus (GDM) exposure and child adiposity.  
Methods: This was a cross-sectional study of 9-10-year-old participants and siblings across the United States. Data was obtained from the baseline assessment of the Adolescent Brain and Cognitive Development (ABCD) Study®. Brain structure was evaluated by magnetic resonance imaging.  GDM exposure was self-reported, and discordance for GDM exposure within biological siblings was identified. Mixed effects and mediation models were used to examine associations between prenatal GDM exposure, brain structure, and adiposity markers with sociodemographic covariates. 
Results: The sample included 8,521 children (7% GDM-exposed), among whom there were 28 sibling pairs discordant for GDM exposure. Across the entire study sample, prenatal exposure to GDM was associated with lower global and regional cortical gray matter volume (GMV) in the bilateral rostral middle frontal gyrus and superior temporal gyrus. GDM-exposed siblings also demonstrated lower global cortical GMV than un-exposed siblings. Global cortical GMV partially mediated the associations between prenatal GDM exposure and child adiposity markers.  
Conclusions: Our results identify brain markers of prenatal GDM exposure and suggest that low cortical GMV may explain increased obesity risk for offspring prenatally exposed to GDM.
DOI: 10.15154/1524765
title: T1w/T2w Ratio and Cognition in 9-to-11-Year-Old Children

description: Childhood is a period of extensive cortical and neural development. Among other things, axons in the brain gradually become more myelinated, promoting the propagation of electrical sig-nals between different parts of the brain, which in turn may facilitate skill development. Myelin is difficult to assess in vivo, and measurement techniques are only just beginning to make their way into standard imaging protocols in human cognitive neuroscience. An approach that has been proposed as an indirect measure of cortical myelin is the T1w/T2w ratio, a contrast that is based on the intensities of two standard structural magnetic resonance images. Although not initially intended as such, researchers have recently started to use the T1w/T2w contrast for between-subject comparisons of cortical data with various behavioral and cognitive indices. As a complement to these earlier findings, we computed individual cortical T1w/T2w maps using data from the Adolescent Brain Cognitive Development study (N = 960; 449 females; aged 8.9 to 11.0 years) and related the T1w/T2w maps to indices of cognitive ability; in contrast to previous work, we did not find significant relationships between T1w/T2w values and cognitive performance after correcting for multiple testing. These findings reinforce existent skepticism about the applicability of T1w/T2w ratio for inter-individual comparisons.
DOI: 10.15154/1524768
title: Associations Between Traumatic Stress, Brain Volumes and Post-traumatic Stress Disorder Symptoms in Children: Data from the ABCD Study

description: Reduced volumes in brain regions of interest (ROIs), primarily from adult samples, are associated with posttraumatic stress disorder (PTSD). We extended this work to children using data from the Adolescent Brain Cognitive Development (ABCD) Study® (N = 11,848; Mage = 9.92). Structural equation modeling and an elastic-net (EN) machine-learning approach were used to identify potential effects of traumatic events (TEs) on PTSD symptoms (PTSDsx) directly, and indirectly via the volumes 300 subcortical and cortical ROIs. We then estimated the genetic and environmental variation in the phenotypes. TEs were directly associated with PTSDsx (r = 0.92) in children, but their indirect effects (r < 0.0004)—via the volumes of EN-identified subcortical and cortical ROIs—were negligible at this age. Additive genetic factors explained a modest proportion of the variance in TEs (23.4%) and PTSDsx (21.3%), and accounted for most of the variance of EN-identified volumes of four of the five subcortical (52.4–61.8%) three of the nine cortical ROIs (46.4–53.3%) and cerebral white matter in the left hemisphere (57.4%). Environmental factors explained most of the variance in TEs (C = 61.6%, E = 15.1%), PTSDsx (residual-C = 18.4%, residual-E = 21.8%), right lateral ventricle (C = 15.2%, E = 43.1%) and six of the nine EN-identified cortical ROIs (C = 4.0–13.6%, E = 56.7–74.8%). There is negligible evidence that the volumes of brain ROIs are associated with the indirect effects of TEs on PTSDsx at this age. Overall, environmental factors accounted for more of the variation in TEs and PTSDsx. Whereas additive genetic factors accounted for most of the variability in the volumes of a minority of cortical and in most of subcortical ROIs.
DOI: 10.15154/1526322
title: Impact of multi-domain environmental factors and behaviors and processes on the developing adolescent connectome

description: Adolescence is a period of profound but incompletely understood changes in the brain's neural circuitry (the connectome), which is vulnerable to risk factors, including insufficient sleep, unhealthy weight and adverse events, but may be protected by positive factors such as a nurturing family environment, positive social factors and healthy sleep behaviors and activity. The effects of these complex and often inter-connected factors remain poorly understood. Using advanced computational techniques from Network Science, Machine Learning and Statistics, and longitudinal data from the ABCD cohort, the goal of this study is to untangle and robustly characterize the differential effects of social factors and physiological processes on the developing connectome, from early adolescence to young adulthood.
DOI: 10.15154/1526351
title: BrainGB: A Benchmark for Brain Network Analysis with Graph Neural Networks

description: Mapping the connectome of the human brain
using structural or functional connectivity has become one
of the most pervasive paradigms for neuroimaging analysis.
Recently, Graph Neural Networks (GNNs) motivated from
geometric deep learning have attracted broad interest due
to their established power for modeling complex networked
data. Despite their established performance in other fields,
there has not yet been a systematic study of how to design
effective GNNs for brain network analysis. To bridge this
gap, we present BrainGB, a benchmark for brain network
analysis with GNNs. BrainGB standardizes the process by
1) summarizing brain network construction pipelines for
both functional and structural neuroimaging modalities and
2) modularizing the implementation of GNN designs. We
conduct extensive experiments on datasets across cohorts
and modalities and recommend a set of general recipes for
effective GNN designs on brain networks.
DOI: 10.15154/1526360
title: Association between asthma and suicidality in 9-11-year-old children

description: Background: Suicidal thoughts and behavior (STB) in children are a growing health concern, and more data is needed regarding their biological underpinnings. Asthma is a common chronic inflammatory disorder in children and has been associated with STB in adolescent and adult populations, but data in children is lacking. We wished to study associations of asthma with childhood suicidality given asthma’s potential as a clinically relevant model for childhood chronic immune dysregulation.
Methods: Using data from the Adolescent Brain Cognitive Development (ABCD) Study (N=11,878, 52% males, mean age 9.9 years at baseline assessment and 10.9 years at 1-year follow up), we assessed associations between asthma and STB at both baseline and 1-year follow up.
Results: We found that asthma at baseline assessment (n=2,214, 18.6%) is associated with STB, controlling for multiple confounders including demographics, socioeconomic factors and environmental confounders such as air pollution (odds ratio (OR)=1.2, 95%CI 1.01-1.42, P=0.039). Indicators of recently active asthma were not significantly associated with suicidality at baseline assessment (currently taking asthma medication: OR=1.22, 95%CI 0.93-1.60, P=0.146), or at 1-year follow up (past year asthma-related clinical visit: OR=1.13, 95%CI 0.87-1.47, P=0.357). Proxy-measures of asthma severity (number of asthma medications or clinical visits) did not reveal a significant dose response relationship with suicidality.  
Limitations: This is a cross-sectional study that does not allow causal inference.
Conclusions: Findings suggest an association between history of asthma and suicidality in children, which may not be related to asthma disease state. Further research is needed to investigate mechanisms underlying this relationship.