cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.15154/1517592
title: Parental and Social Factors in relation to Child Psychopathology, Behavior, and Cognitive Function

description: Parental and social factors have long-term impact on the neurodevelopment of offspring, but tend to highly covary with each other. Thus, it is difficult to parse out which parental and social factor contributes most to neurodevelopmental outcomes. This study aimed to assess clusters of parental and social factors associated with child psychopathology, behavioral problems, and cognition. This study employed the data of 11,875 children (9-to-11 years) from the Adolescent Brain Cognitive Development (ABCD) study. Principal component analysis (PCA) was performed on 39 environmental measures and 30 child behavior and cognitive measures separately to identify clusters of parental and social factors and clusters of child psychopathology, behaviour, and cognition. Regression analysis was used to examine independent effects of each cluster of parental and social factors on child psychopathology, behavioral problems, and cognition. Greater Parent Psychopathology cluster was associated with greater Child Psychopathology cluster. Moreover, greater Socioeconomic Status cluster was associated with greater child General Cognition and Executive Function but less Behavioral Inhibition clusters. Greater Proximal Social Environment and Interaction cluster were associated with less child Impulsive Behavior and Behavioral Inhibition, but greater Behavioral Activation cluster. The environmental clusters related to birth outcomes, maternal tobacco, and drug use were not significantly related to child psychopathology, behavior, and cognition. Our findings suggest that socioeconomic status, parental psychopathology, and social environment and interactions are the strongest risks for behavioral problems and cognitive performance in a general child population. Intervention programs should target modifiable factors within these domains.
DOI: 10.15154/1519021
title: Caffeine intake and cognitive functions in children

description: Rationale: There is a growing concern over excessive caffeine use and the development of caffeine use disorder in children.
Objectives: This study aimed to identify the association between caffeine intake and cognitive functioning in children.
Methods: This study included 11,718 youths aged 9–10 years with cognitive and caffeine intake information that were extracted from the Adolescent Brain Cognitive Development (ABCD) study. The ABCD study is a longitudinal cohort study that started in 2017 that aims to understand the relationships between substance use and neurocognition in youths living in the USA. Cognitive measures were obtained through the 7 core cognitive instruments from the NIH toolbox (vocabulary comprehension, reading decoding, inhibitory control, working memory, cognitive flexibility, processing speed, and episodic memory). Associations between caffeine intake and the seven cognitive functions were examined using multiple regression models.
Results: Our study revealed that caffeine intake negatively correlated with all the seven cognitive measures. After adjustment for age, gender, sleep, and socioeconomic status (SES), caffeine intake was still found to be negatively associated with most of the cognitive functions, such as vocabulary comprehension, working memory, cognitive flexibility, processing speed, and episodic memory, except reading decoding, and inhibitory control.
Conclusions: As beverages with caffeine are consumed frequently, controlling their intake may reduce risk for nonoptimal cognitive development in children.
DOI: 10.15154/1520624
title: Psychotic-like experiences and polygenic liability in the ABCD Study®

description: Background: The current study examined whether psychotic-like experiences (PLEs) during childhood are associated with several psychopathology-related polygenic scores (PGS) generally associated with psychopathology (e.g., psychosis) risk, and additionally examined possible neural and behavioral mechanisms for significant associations. 
Methods: Adolescent Brain Cognitive Development℠ Study baseline data from children with European ancestry (n=4,650; ages 9-10; 46.8% female) were used to estimate associations between PLEs (i.e., both total and presence of significantly distressing) and PGS for psychopathology (i.e., schizophrenia, psychiatric cross-disorder risk, PLEs) and related phenotypes (i.e., educational attainment [EDU]), birth-weight, inflammation). We also assessed evidence that variability in brain structure indices (i.e., volume, cortical thickness, surface area), as well as behaviors proximal to PGS (e.g., cognition for EDU), indirectly linked PGS to PLEs using mediational models. 
Results: Total and significantly distressing PLEs were associated with EDU and cross-disorder PGS (all %ΔR2s=0.202-0.660%; pFDRs<0.006). Significantly distressing PLEs were also associated with higher schizophrenia and PLEs PGS (both %ΔR2=0.120-0.171%; pFDRs<0.03). There was evidence consistent with global brain volume metrics and cognitive performance indirectly linking EDU PGS to PLEs (proportion mediated:3.33-32.22%). 
Conclusions: Total and significantly distressing PLEs were associated with genomic risk indices associated with broad-spectrum psychopathology risk (i.e., EDU and cross-disorder PGS). Significantly distressing PLEs were associated with genomic risk for psychosis (i.e., schizophrenia, PLEs). Global brain volume metrics and PGS-proximal behaviors represent promising putative intermediary phenotypes that may contribute to genomic risk for psychopathology. Broadly, polygenic scores derived from genome-wide association studies of adult samples generalize to indices of psychopathology risk among children.
DOI: 10.15154/1520789
title: The role of family conflict in mediating impulsivity to early substance exposure among preteens

description: Objectives: Preadolescence substance exposure, which increases the risk of regular substance use, has been a public health concern. Although studies found that impulsivity is a predisposing factor of early substance exposure, the pathways through which impulsivity is associated with early substance exposure remain unclear. This study examined how family conflict mediates this association among U.S. preteens as family environment plays an essential role in pre-adolescent development.

Methods: Respondents (N = 11,800, 9–10 years old) from the Adolescent Brain Cognitive Development (ABCD) Study Release 2.01 (July 2019) were included in this study. Generalized structural equation modeling was performed to investigate the mediation effects of family conflict on the associations between childhood impulsivity and early exposure to alcohol and tobacco use, controlling for covariates based on the Problem Behavior Theory.

Results: Pre-adolescents with high impulsivity levels (≥90th percentile) were more likely to report early alcohol and tobacco exposure (total effect: ORs = 1.49 and 1.70, respectively), where 4.13% and 12.41% of the associations, respectively, were meditated by family conflict (indirect effect: ORs = 1.02 and 1.07; Sobel test ps = 0.022 and 0.005, respectively).

Conclusions: Family conflict mediates the associations between childhood impulsivity and early substance exposure among preteens, with higher impulsivity leading to more severe family conflicts that are, in turn, associated with a higher likelihood of early substance exposure. To prevent preteens with high impulsivity level from early use of substances, interventions may focus on reducing family conflicts such as parenting counseling that guides parents to strengthen conflict-resolution skills and create a stable home environment for preteens.
DOI: 10.15154/1520882
title: Physical Fitness, Cognition, and Structural Network Efficiency of Brain Connections Across the Lifespan

description: Inadequate levels of exercise is one of the most potent modifiable risk factors for preventing cognitive decline and dementia as we age. Meanwhile, network science-based measures of structural brain network global and local efficiency show promise as robust biomarkers of aging, cognitive decline, and pathological disease progression. Despite this, little to no work has established how maintaining physical activity (PA) and physical fitness might relate to cognition and network efficiency measures across the lifespan. Therefore the purpose of this study was to determine the relationship between (1) PA and fitness and cognition, (2) fitness and network efficiency, and (3) how network efficiency measures relate to cognition. To accomplish this, we analyzed a large cross-sectional data set (n=720; 36-100 years) from the aging human connectome project, which included the Trail Making Task (TMT) A and B, a measure of fitness (2-minute walk test), physical activity (International Physical Activity Questionnaire), and high-resolution diffusion imaging data. Our analysis consisted of employing multiple linear regression while controlling for age, sex, and education. Age was associated with lower global and local brain network efficiency and poorer Trail A & B performance. Meanwhile, fitness, but not physical activity, was related to better Trail A and B performance and fitness, and was positively associated with local and global brain efficiency. Finally, local efficiency was related to better TMT B performance and partially mediated the relationship between fitness and TMT B performance. These results indicate aging may be associated with a shift towards less efficient local and global neural networks and that maintaining physical fitness might protect against age-related cognitive performance deterioration by bolstering structural network efficiency.
DOI: 10.15154/1521162
title: Examining Reaction Time Variability on the Stop Signal Task in the ABCD Study

description: Objective: Reaction time variability (RTV) has been estimated using Gaussian, ex-Gaussian, and diffusion model (DM) indices. Rarely have studies examined inter-relationships among these performance indices in childhood, and the use of reaction time (RT) computational models have been slow to take hold in the developmental psychopathology literature. Here, we extend prior work in adults by examining the inter-relationships among different model parameters in the ABCD sample and demonstrate how computational models of RT can clarify mechanisms of time-on-task effects and sex differences in RTs. 
Method: This study utilized trial-level data from the Stop-Signal Task from 8916 children (9-10 years old) to examine Gaussian, ex-Gaussian, and DM indicators of RTV. In addition to describing RTV patterns, we examined inter-relations amongst these indicators, temporal patterns, and sex differences. 
Results: There was no one-to-one correspondence between DM and ex-Gaussian parameters. Nonetheless, drift rate was most strongly associated with standard deviation of RT and tau, while non-decisional processes were most strongly associated with RT, mu, and sigma. Performance worsened across time with changes driven primarily by decreasing drift rate. Boys were faster and less variable than girls, likely attributable to girls’ wide boundary separation. 
Conclusions: Intercorrelations among model parameters are similar in children as has been observed in adults. Computational approaches play a crucial role in understanding performance changes over time and can also clarify mechanisms of group differences. For example, standard RT models may incorrectly suggest slowed processing speed in girls that is actually attributable to other factors.

Note: The subject level reaction time variability data used in this study can be accessed through the collection Parsing Neurobiological Bases of Heterogeneity in ADHD (C3605) https://nda.nih.gov/edit_collection.html?id=3605
DOI: 10.15154/1522579
title: Randomized Trials with Repeatedly Measured Outcomes: Handling Irregular and Potentially Informative Assessment Times

description: Randomized trials are often designed to collect outcomes at fixed points in time after randomization.  In practice, the number and timing of outcome assessments can vary among participants. (i.e., irregular).  In fact, the timing of assessments may be associated with the outcome of interest (i.e., informative).  For example, in a trial evaluating the effectiveness of housing services for homeless people with mental illness, not only did the timings of outcome measurements vary among participants, but more days spent homeless were associated with less frequent observation. This type of informative observation requires appropriate statistical analysis. While analytic methods have been developed, they are rarely used. 

The purpose of this paper is to review the methods available with a view to developing recommendations for analyzing trials with irregular and potentially informative observation times. We show how the choice of analytic approach hinges on assumptions about the relationship between the observation and outcome processes. We argue that irregular observation should be treated with the same care as missing data, and propose that trialists: adopt strategies to minimize the extent of irregularity; describe the extent of irregularity in observation times; make their assumptions about the relationships between observation times and outcomes explicit; adopt analytic techniques that are appropriate to their assumptions; rigorously assess sensitivity of trial results to their assumptions.
DOI: 10.15154/1522677
title: Trauma, posttraumatic stress disorder, and treatment among middle-aged and older women in the Nurses’ Health Study II

description: Objectives: Trauma and posttraumatic stress disorder (PTSD) are common among women and associated with negative health outcomes across the life course. Relatively few studies, however, have examined the epidemiology of trauma, PTSD, and treatment among middle-aged and older civilian women, who are at elevated risk for adverse health outcomes. We aimed to characterize trauma, PTSD, and trauma-related treatment prevalence and correlates in a large cohort of middle-aged and older women. Design: Cross-sectional, nested sub-study within the Nurses’ Health Study II cohort. Setting: United States, 2018-2020. Participants: 33,327 current or former nurses, aged 53-74 years. Measurements: 16-item modified version of the Brief Trauma Questionnaire; modified PTSD Checklist for the Diagnostic and Statistical Manual, Version 5. Results: The majority (82.2%) of women reported one or more lifetime traumas. The most common trauma types were unexpected death of a loved one (44.9%) and interpersonal violence (43.5%). Almost 30% reported occupational (nursing-related) trauma. Among the trauma-exposed, 10.5% met criteria for lifetime PTSD and 1.5% had past-month PTSD. One-third of lifetime PTSD cases were due to interpersonal violence event types. One-third of women with lifetime PTSD—and nearly half of those with PTSD from a nursing-related trauma—reported never receiving trauma-related treatment. Women aged 65 years and older with PTSD were less likely to be in treatment than those aged less than 65 years.  Conclusions: History of trauma and PTSD is prevalent in this population, and a treatment gap persists. Addressing this treatment gap is warranted, particularly among older women and those with nursing-related trauma.
DOI: 10.15154/1522907
title: Prevalence of Perceived Racism and Discrimination Among US Children Aged 10 and 11 Years: The Adolescent Brain Cognitive Development (ABCD) Study

description: This cross-sectional study uses data from the Adolescent Brain Cognitive Development Study to assess the prevalence of perceived racism and discrimination among US children aged 10 through 11 years.
DOI: 10.15154/1523379
title: Associations Between Brain Structural Alterations, Executive Dysfunction, and General Psychopathology in a Healthy and Cross-Diagnostic Adult Patient Sample

description: A general psychopathology factor (p factor) captures shared variance across mental disorders in diverse samples and may partly reflect executive dysfunction. Higher p factor scores have been related to structural alterations within the visual association cortex (VAC) and a cerebello-thalamo-cerebro-cortical circuit, both of which are important for executive control. Here, we tested replicability of these direct associations as well as the indirect role of executive functioning in a sample of healthy and cross-diagnostic adult patients. We conducted hypothesis-driven (i.e., region of interest) and exploratory whole-brain structural neuroimaging analyses using data from the Consortium for Neuropsychiatric Phenomics (CNP) study of 272 adults who met diagnostic criteria for schizophrenia, bipolar disorder, or attention-deficit/hyperactivity disorder or were healthy control subjects. Using structural equation modeling, we examined direct and indirect relations between structural neural alterations (within regions of interest and regions identified from exploratory analyses) and p and executive function factors. Higher levels of the p factor were associated with decreased executive functioning and VAC gray matter volume, replicating previous research. In contrast, we failed to replicate previous negative relations between the p factor and cerebello-thalamo-cerebro-cortical circuit structure. A significant indirect relation between VAC gray matter volume and the p factor via executive function also emerged. Whole-brain analyses identified additional structural alterations in supplementary motor area/cingulate cortex, anterior corona radiata, and corpus callosum genu related to the p factor. Executive dysfunction may be one mechanism underlying relations between brain structure and general psychopathology. Replication of VAC structural alterations related to the p factor encourages further focus on this brain structure.
DOI: 10.15154/1524461
title: ABCD_Harmonizer: An Open‑source Tool for Mapping and Controlling for Scanner Induced Variance in the Adolescent Brain Cognitive Development Study

description: Data from multisite magnetic resonance imaging (MRI) studies contain variance attributable to the scanner that can reduce statistical power and potentially bias results if not appropriately managed. The Adolescent Cognitive Brain Development (ABCD) study is an ongoing, longitudinal neuroimaging study acquiring data from over 11,000 children starting at 9–10 years of age. These scans are acquired on 29 different scanners of 5 different model types manufactured by 3 different vendors. Publicly available data from the ABCD study include structural MRI (sMRI) measures such as cortical thickness and diffusion MRI (dMRI) measures such as fractional anisotropy. In this work, we 1) quantify the variance attributable to scanner effects in the sMRI and dMRI datasets, 2) demonstrate the effectiveness of the data harmonization approach called ComBat to address scanner effects, and 3) present a simple, open-source tool for investigators to harmonize image features from the ABCD study. Scanner-induced variance was present in every image feature and varied in magnitude by feature type and brain location. For almost all features, scanner variance exceeded variability attributable to age and sex. ComBat harmonization was shown to effectively remove scanner induced variance from all image features while preserving the biological variability in the data. Moreover,
we show that for studies examining relatively small subsamples of the ABCD dataset, the use of ComBat harmonized data provides more accurate estimates of effect sizes compared to controlling for scanner effects using ordinary least squares regression.
DOI: 10.15154/1524635
title: Efficient reconstruction of cell lineage trees for cell ancestry and cancer

description: Mosaic mutations can be used to track cell ancestries and reconstruct high-resolution lineage trees during cancer progression and during development, starting from the first cell divisions of the zygote. However, this approach requires sampling and analyzing the genomes of multiple cells, which can be redundant in lineage representation, limiting the scalability of the approach. We describe a strategy for cost- and time-efficient lineage reconstruction using clonal induced pluripotent stem cell lines from human skin fibroblasts. The approach leverages shallow sequencing coverage to assess the clonality of the lines, clusters redundant lines and sums their coverage to accurately discover mutations in the corresponding lineages. Only a fraction of lines needs to be sequenced to high coverage. We demonstrate the effectiveness of this approach for reconstructing lineage trees during development and in hematologic malignancies. We discuss and propose an optimal experimental design for reconstructing lineage trees.
DOI: 10.15154/1524636
title: Association Between Discrimination Stress and Suicidality in Preadolescent Children

description: Objective: Youth suicide rates in the United States have been increasing in recent years, especially in Black Americans, the reasons for which are unclear. Environmental adversity is key in youth suicidality; hence there is a need to study stressors that have a disproportionate impact on Black youths. We aimed to disentangle the unique contribution of racial/ethnic discrimination from other adversities associated with childhood suicidal ideation and attempts (suicidality).

Method: We analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study, which included a large, diverse sample of US children (N 1⁄4 11,235, mean age 10.9 years, 20.2% Black), assessed for multiple environmental adversities including discrimination. Multivariate regression models tested the association of self-reported racial/ethnic discrimination with suicidality, covarying for multiple confounders including other discrimination types (toward nonUS-born individuals, sexual orientationbased, and weight-based). Matched analyses contrasted effects of racial/ ethnic discrimination and racial identity on suicidality.

Results: Black youths reported more discrimination and higher suicidality rates than non-Black youths. High racial/ethnic discrimination was positively and significantly associated with suicidality, adjusting for other discrimination types (odds ratio 1⁄4 2.6, 95% CI 1⁄4 2.13.2). Findings remained significant after adjusting for multiple suicidality risk factors. Once experienced, racial/ethnic discrimination was similarly associated with suicidality in White, Black, and Hispanic youths. Matched analyses revealed that racial/ethnic discrimination was associated with suicidality (relative risk 1⁄4 2.7, 95% CI 1⁄4 23.5), whereas Black race was not (relative risk 1⁄4 0.9, 95% CI 1⁄4 0.71.2).

Conclusion: Racial/ethnic discrimination is disproportionately experienced by Black children, and is associated with preadolescent suicidality, over and above other adversities. Findings highlight the need to address discrimination as part of suicide prevention strategies. Cross-sectional design hampers causal inferences.