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Early adolescent drinking onset is linked to myriad negative consequences. Using the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) baseline to year 8 data, this study (1) leveraged best subsets selection and Cox Proportional Hazards regressions to identify the most robust predictors of adolescent first and regular drinking onset, and (2) examined the clinical utility of drinking onset in forecasting later binge drinking and withdrawal effects. Baseline predictors included youth psychodevelopmental characteristics, cognition, brain structure, family, peer, and neighborhood domains. Participants (N=538) were alcohol-naïve at baseline. The strongest predictors of first and regular drinking onset were positive alcohol expectancies (Hazard Ratios [HRs]=1.67-1.87), easy home alcohol access (HRs=1.62-1.67), more parental solicitation (e.g., inquiring about activities; HRs=1.72-1.76), and less parental control and knowledge (HRs=.72-.73). Robust linear regressions showed earlier first and regular drinking onset predicted earlier transition into binge and regular binge drinking (βs=0.57-0.95). Zero-inflated Poisson regressions revealed that delayed first and regular drinking increased the likelihood (Incidence Rate Ratios [IRR]=1.62 and IRR=1.29, respectively) of never experiencing withdrawal. Findings identified behavioral and environmental factors predicting temporal paths to youthful drinking, dissociated first from regular drinking initiation, and revealed adverse sequelae of younger drinking initiation, supporting efforts to delay drinking onset.

Heavy alcohol drinking is a major, preventable problem that adversely impacts the physical and mental health of US young adults. Studies seeking drinking risk factors typically focus on young adults who enrolled in 4-year residential college programs (4YCP) even though most high school graduates join the workforce, military, or community colleges. We examined 106 of these understudied young adults (USYA) and 453 4YCPs from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) by longitudinally following their drinking patterns for 8 years from adolescence to young adulthood. All participants were no-to-low drinkers during high school. Whereas 4YCP individuals were more likely to initiate heavy drinking during college years, USYA participants did so later. Using mental health metrics recorded during high school, machine learning forecasted individual-level risk for initiating heavy drinking after leaving high school. The risk factors differed between demographically matched USYA and 4YCP individuals and between sexes. Predictors for USYA drinkers were sexual abuse, physical abuse for girls, and extraversion for boys, whereas 4YCP drinkers were predicted by the ability to recognize facial emotion and, for boys, greater openness. Thus, alcohol prevention programs need to give special consideration to those joining the workforce, military, or community colleges, who make up the majority of this age group.

Abstract: Claiming causal inferences in network settings necessitates careful consideration of the often complex dependency between outcomes for actors. Of particular importance are treatment spillover or outcome interference effects. We consider causal inference when the actors are connected via an underlying network structure. Our key contribution is a model for causality when the underlying network is endogenous; where the ties between actors and the actor covariates are statistically dependent. We develop a joint model for the relational and covariate generating process that avoids restrictive separability and fixed network assumptions, as these rarely hold in realistic social settings. While our framework can be used with general models, we develop the highly expressive class of Exponential-family Random Network models (ERNM) of which Markov random fields and Exponential-family Random Graph models are special cases. We present potential outcome-based inference within a Bayesian framework and propose a modification to the exchange algorithm to allow for sampling from ERNM posteriors. We present results of a simulation study demonstrating the validity of the approach. Finally, we demonstrate the value of the framework in a case study of smoking in the context of adolescent friendship networks.

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or Long COVID) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIHs REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Background and aimsRecently, we demonstrated that a distinct pattern of structural covariance networks (SCN) from magnetic resonance imaging (MRI)-derived measurements of brain cortical thickness characterized young adults with alcohol use disorder (AUD) and predicted current and future problematic drinking in adolescents relative to controls. Here, we establish the robustness and value of SCN for identifying heavy alcohol users in three additional independent studies.Design and settingCross-sectional and longitudinal studies using data from the Pediatric Imaging, Neurocognition and Genetics (PING) study (n = 400, age range = 14-22 years), the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) (n = 272, age range = 17-22 years) and the Human Connectome Project (HCP) (n = 375, age range = 22-37 years).CasesCases were defined based on heavy alcohol use patterns or former alcohol use disorder (AUD) diagnoses: 50, 68 and 61 cases were identified. Controls had none or low alcohol use or absence of AUD: 350, 204 and 314 controls were selected.MeasurementsGraph theory metrics of segregation and integration were used to summarize SCN.FindingsMirroring our prior findings, and across the three data sets, cases had a lower clustering coefficient [area under the curve (AUC) = -0.029, P = 0.002], lower modularity (AUC = -0.14, P = 0.004), lower average shortest path length (AUC = -0.078, P = 0.017) and higher global efficiency (AUC = 0.007, P = 0.010). Local efficiency differences were marginal (AUC = -0.017, P = 0.052). That is, cases exhibited lower network segregation and higher integration, suggesting that adjacent nodes (i.e. brain regions) were less similar in thickness whereas spatially distant nodes were more similar.ConclusionStructural covariance network (SCN) differences in the brain appear to constitute an early marker of heavy alcohol use in three new data sets and, more generally, demonstrate the utility of SCN-derived metrics to detect brain-related psychopathology.

Subcortical brain morphometry matures across adolescence and young adulthood, a time when many youth engage in escalating levels of alcohol use. Initial cross-sectional studies have shown alcohol use is associated with altered subcortical morphometry. However, longitudinal evidence of sex-specific neuromaturation and associations with alcohol use remains limited. This project used generalized additive mixed models to examine sex-specific development of subcortical volumes and associations with recent alcohol use, using 7 longitudinal waves (n = 804, 51% female, ages 12-21 at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA). A second, independent, longitudinal dataset, with up to four waves of data (n = 467, 43% female, ages 10-18 at baseline), was used to assess replicability. Significant, replicable non-linear normative volumetric changes with age were evident in the caudate, putamen, thalamus, pallidum, amygdala and hippocampus. Significant, replicable negative associations between subcortical volume and alcohol use were found in the hippocampus in all youth, and the caudate and thalamus in female but not male youth, with significant interactions present in the caudate, thalamus and putamen. Findings suggest a structural vulnerability to alcohol use, or a predisposition to drink alcohol based on brain structure, with female youth potentially showing heightened risk, compared to male youth.

Study objectivesAdolescence is characterized by significant brain development, accompanied by changes in sleep timing and architecture. It also is a period of profound psychosocial changes, including the initiation of alcohol use; however, it is unknown how alcohol use affects sleep architecture in the context of adolescent development. We tracked developmental changes in polysomnographic (PSG) and electroencephalographic (EEG) sleep measures and their relationship with emergent alcohol use in adolescents considering confounding effects (e.g. cannabis use).MethodsAdolescents (n = 94, 43% female, age: 12-21 years) in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study had annual laboratory PSG recordings across 4-years. Participants were no/low drinkers at baseline.ResultsLinear mixed effect models showed developmental changes in sleep macrostructure and EEG, including a decrease in slow wave sleep and slow wave (delta) EEG activity with advancing age. Emergent moderate/heavy alcohol use across three follow-up years was associated with a decline in percentage rapid eye movement (REM) sleep over time, a longer sleep onset latency (SOL) and shorter total sleep time (TST) in older adolescents, and lower non-REM delta and theta power in males.ConclusionsThese longitudinal data show substantial developmental changes in sleep architecture. Emergent alcohol use during this period was associated with altered sleep continuity, architecture, and EEG measures, with some effects dependent on age and sex. These effects, in part, could be attributed to the effects of alcohol on underlying brain maturation processes involved in sleep-wake regulation.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has significantly increased depression rates, particularly in emerging adults. The aim of this study was to examine longitudinal changes in depression risk before and during COVID-19 in a cohort of emerging adults in the U.S. and to determine whether prior drinking or sleep habits could predict the severity of depressive symptoms during the pandemic.MethodsParticipants were 525 emerging adults from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a five-site community sample including moderate-to-heavy drinkers. Poisson mixed-effect models evaluated changes in the Center for Epidemiological Studies Depression Scale (CES-D-10) from before to during COVID-19, also testing for sex and age interactions. Additional analyses examined whether alcohol use frequency or sleep duration measured in the last pre-COVID assessment predicted pandemic-related increase in depressive symptoms.ResultsThe prevalence of risk for clinical depression tripled due to a substantial and sustained increase in depressive symptoms during COVID-19 relative to pre-COVID years. Effects were strongest for younger women. Frequent alcohol use and short sleep duration during the closest pre-COVID visit predicted a greater increase in COVID-19 depressive symptoms.ConclusionsThe sharp increase in depression risk among emerging adults heralds a public health crisis with alarming implications for their social and emotional functioning as this generation matures. In addition to the heightened risk for younger women, the role of alcohol use and sleep behavior should be tracked through preventive care aiming to mitigate this looming mental health crisis.

Cortical thickness changes dramatically during development and is associated with adolescent drinking. However, previous findings have been inconsistent and limited by region-of-interest approaches that are underpowered because they do not conform to the underlying spatially heterogeneous effects of alcohol. In this study, adolescents (n = 657; 12-22 years at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study who endorsed little to no alcohol use at baseline were assessed with structural magnetic resonance imaging and followed longitudinally at four yearly intervals. Seven unique spatial patterns of covarying cortical thickness were obtained from the baseline scans by applying an unsupervised machine learning method called non-negative matrix factorization (NMF). The cortical thickness maps of all participants' longitudinal scans were projected onto vertex-level cortical patterns to obtain participant-specific coefficients for each pattern. Linear mixed-effects models were fit to each pattern to investigate longitudinal effects of alcohol consumption on cortical thickness. We found in six NMF-derived cortical thickness patterns, the longitudinal rate of decline in no/low drinkers was similar for all age cohorts. Among moderate drinkers the decline was faster in the younger adolescent cohort and slower in the older cohort. Among heavy drinkers the decline was fastest in the younger cohort and slowest in the older cohort. The findings suggested that unsupervised machine learning successfully delineated spatially coordinated patterns of vertex-level cortical thickness variation that are unconstrained by neuroanatomical features. Age-appropriate cortical thinning is more rapid in younger adolescent drinkers and slower in older adolescent drinkers, an effect that is strongest among heavy drinkers.

BackgroundAccurate measurement of trajectories in longitudinal studies, considered the gold standard method for tracking functional growth during adolescence, decline in aging, and change after head injury, is subject to confounding by testing experience.MethodsWe measured change in cognitive and motor abilities over four test sessions (baseline and three annual assessments) in 154 male and 165 female participants (baseline age 12-21 years) from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study. At each of the four test sessions, these participants were given a test battery using computerized administration and traditional pencil and paper tests that yielded accuracy and speed measures for multiple component cognitive (Abstraction, Attention, Emotion, Episodic memory, Working memory, and General Ability) and motor (Ataxia and Speed) functions. The analysis aim was to dissociate neurodevelopment from testing experience by using an adaptation of the twice-minus-once tested method, which calculated the difference between longitudinal change (comprising developmental plus practice effects) and practice-free initial cross-sectional performance for each consecutive pairs of test sessions. Accordingly, the first set of analyses quantified the effects of learning (i.e., prior test experience) on accuracy and after speed domain scores. Then developmental effects were  determined for each domain for accuracy and speed having removed the measured learning effects.ResultsThe greatest gains in performance occurred between the first and second sessions, especially in younger participants, regardless of sex, but practice gains continued to accrue thereafter for several functions. For all 8 accuracy composite scores, the developmental effect after accounting for learning was significant across age and was adequately described by linear fits. The learning-adjusted developmental effects for speed were adequately described by linear fits for Abstraction, Emotion, Episodic Memory, General Ability, and Motor scores, although a nonlinear fit was better for Attention, Working Memory, and Average Speed scores.ConclusionThus, what appeared as accelerated cognitive and motor development was, in most cases, attributable to learning. Recognition of the substantial influence of prior testing experience is critical for accurate characterization of normal development and for developing norms for clinical neuropsychological investigations of conditions affecting the brain.

ObjectiveIndividual differences in adolescent personality are related to a variety of long-term health outcomes. While previous studies have demonstrated sex differences and non-linear changes in personality development, these results remain equivocal. The current study utilized longitudinal data (n = 831) from the National Consortium on Alcohol and Neurodevelopment in Adolescence to examine sex differences in the development of personality and the association between substance use and personality.MethodParticipants (ages 12-21 at baseline) completed the Ten-Item Personality Inventory and self-reported past year alcohol and marijuana use at up to 7 yearly visits. Data were analyzed using generalized additive mixed-effects models and linear mixed-effects models.ResultsFindings support linear increases in agreeableness and conscientious and decreases in openness with age and inform on timing of sex-specific non-linear development of extraversion and emotional stability. Further, results provide novel information regarding the timing of the association between substance use and personality, and replicate past reporting of differential associations between alcohol and marijuana use and extraversion, and sex-dependent effects of marijuana use on emotional stability.ConclusionsThese findings highlight the importance of modeling sex differences in personality development using flexible non-linear modeling strategies, and accounting for sex- and age-specific effects of alcohol and marijuana use.

ObjectiveThis study examined the impact of the COVID-19 pandemic on drinking and nicotine use through June of 2021 in a community-based sample of young adults.MethodData were from 348 individuals (49% female) enrolled in a long-term longitudinal study with an accelerated longitudinal design: the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) Study. Individuals completed pre-pandemic assessments biannually from 2016 to early 2020, then completed up to three web-based, during-pandemic surveys in June 2020, December 2020, and June 2021. Assessments when individuals were 18.8-22.4 years old (N = 1,458) were used to compare drinking and nicotine use pre-pandemic vs. at each of the three during-pandemic timepoints, adjusting for the age-related increases expected over time.ResultsCompared to pre-pandemic, participants were less likely to report past-month drinking in June or December 2020, but there was an increase in drinking days among drinkers in June 2020. By June 2021, both the prevalence of past-month drinking and number of drinking days among drinks were similar to pre-pandemic levels. On average, there were no statistically significant differences between pre-pandemic and during-pandemic time points for binge drinking, typical drinking quantity, or nicotine use. Young adults who reported an adverse financial impact of the pandemic showed increased nicotine use while their peers showed stable or decreased nicotine use.ConclusionInitial effects of the pandemic on alcohol use faded by June 2021, and on average there was little effect of the pandemic on nicotine use.

BackgroundGrowing evidence indicates that sleep characteristics predict future substance use and related problems. However, most prior studies assessed a limited range of sleep characteristics, studied a narrow age span, and included few follow-up assessments. Here, we used six annual assessments from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study, which spans adolescence and young adulthood with an accelerated longitudinal design, to examine whether multiple sleep characteristics in any year predict alcohol and cannabis use the following year.MethodsThe sample included 831 NCANDA participants (423 females; baseline age 12-21 years). Sleep variables included circadian preference, sleep quality, daytime sleepiness, the timing of midsleep (weekday/weekend), and sleep duration (weekday/weekend). Using generalized linear mixed models (logistic for cannabis; ordinal for binge severity), we tested whether each repeatedly measured sleep characteristic (years 0-4) predicted substance use (alcohol binge severity or cannabis use) the following year (years 1-5), covarying for age, sex, race, visit, parental education, and previous year's substance use.ResultsGreater eveningness, more daytime sleepiness, later weekend sleep timing, and shorter sleep duration (weekday/weekend) all predicted more severe alcohol binge drinking the following year. Only greater eveningness predicted a greater likelihood of any cannabis use the following year. Post-hoc stratified exploratory analyses indicated that some associations (e.g., greater eveningness and shorter weekend sleep duration) predicted binge severity only in female participants, and that middle/high school versus post-high school adolescents were more vulnerable to sleep-related risk for cannabis use.ConclusionsOur findings support the relevance of multiple sleep/circadian characteristics in the risk for future alcohol binge severity and cannabis use. Preliminary findings suggest that these risk factors vary based on developmental stage and sex. Results underscore a need for greater attention to sleep/circadian characteristics as potential risk factors for substance use in youth and may inform new avenues to prevention and intervention.

Exponential-family Random Graph models (ERGM) are widely used in social network analysis when modelling data on the relations between actors. ERGMs are typically interpreted as a snapshot of a network at a given point in time or in a final state. The recently proposed Latent Order Logistic model (LOLOG) directly allows for a latent network formation process. We assess the real-world performance of these models when applied to typical networks modelled by researchers. Specifically, we model data from an ensemble of articles in the journal Social Networks with published ERGM fits, and compare the ERGM fit to a comparable LOLOG fit. We demonstrate that the LOLOG models are, in general, in qualitative agreement with the ERGM models, and provide at least as good a model fit. In addition they are typically faster and easier to fit to data, without the tendency for degeneracy that plagues ERGMs. Our results support the general use of LOLOG models in circumstances where ERGMs are considered.

To determine the persistent effects of the pandemic on mental health in young adults, we categorized depressive symptom trajectories and sought factors that promoted a reduction in depressive symptoms in high-risk individuals. Specifically, longitudinal analysis investigated changes in the risk for depression before and during the pandemic until December 2021 in 399 young adults (57% female; age range: 22.8 ± 2.6 years) in the United States (U.S.) participating in the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study. The Center for Epidemiologic Studies Depression Scale (CES-D-10) was administered multiple times before and during the pandemic. A score ≥10 identified individuals at high-risk for depression. Self-reported sleep behavior, substance use, and coping skills at the start of the pandemic were assessed as predictors for returning to low-risk levels while controlling for demographic factors. The analysis identified four trajectory groups regarding depression risk, with 38% being at low-risk pre-pandemic through 2021, 14% showing persistent high-risk pre-pandemic through 2021, and the remainder converting to high-risk either in June 2020 (30%) or later (18%). Of those who became high-risk in June 2020, 51% were no longer at high-risk in 2021. Logistic regression revealed that earlier bedtime and, for the older participants (mid to late twenties), better coping skills were associated with this declining risk. Results indicate divergence in trajectories of depressive symptoms, with a considerable number of young adults developing persistent depressive symptoms. Healthy sleep behavior and specific coping skills have the potential to promote remittance from depressive symptoms in the context of the pandemic.

ObjectiveExecutive control continues to develop throughout adolescence and is vulnerable to alcohol use. Although longitudinal assessment is ideal for tracking executive function development and onset of alcohol use, prior testing experience must be distinguished from developmental trajectories.MethodWe used the Stroop Match-to-Sample task to examine the improvement of processing speed and specific cognitive and motor control over 4 years in 445 adolescents. The twice-minus-once-tested method was used and expanded to four test sessions to delineate prior experience (i.e., learning) from development. A General Additive Model evaluated the predictive value of age and sex on executive function development and potential influences of alcohol use on development.ResultsResults revealed strong learning between the first two assessments. Adolescents significantly improved their speed processing over 4 years. Compared with boys, girls enhanced ability to control cognitive interference and motor reactions. Finally, the influence of alcohol use initiation was tested over 4 years for development in 110 no/low, 110 moderate/heavy age- and sex-matched drinkers; alcohol effects were not detected in the matched groups.ConclusionsEstimation of learning effects is crucial for examining developmental changes longitudinally. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

IntroductionIn adolescents, the relationship between alcohol-related blackouts (ARBs) and distinct cognitive changes lasting beyond intoxication is unclear. We examined ARBs as a predictor of persistent changes in the development of learning, memory, and executive function in participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study.MethodsDescriptive analyses of the NCANDA sample (N = 831, 50.9% female, 12-21 years at baseline) identified ARB patterns within participants with an ARB history (n = 106). Latent growth curve modeling evaluated ARB-related performance changes on four neuropsychological measures across five years, excluding baseline data to reduce the magnitude of practice effects over time (n = 790). Measures included the Penn Conditional Exclusion Test (PCET), Penn Letter N-back Test (PLBT), Penn Facial Memory Test immediate (PFMTi), and delayed (PFMTd) recognition trials, and the Rey Complex Figure Test copy (RCFTc), immediate recall (RCFTi), and delayed recall (RCFTd) trials. Multivariate models were fit for raw accuracy scores from each measure, with ARB history (i.e., presence of past-year ARBs) as the main independent variable. Age, sex, race, socioeconomic status, assessment site, and alcohol use (i.e., past-year frequency) were included as covariates. Interaction effects between ARB history and alcohol use frequency were tested.ResultsBy year five, 16% of participants had experienced at least one ARB (59% of whom reported > 1 ARB and 57% of whom had an ARB lasting > 1 h). After controlling for demographics and alcohol use, ARB history predicted attenuated PFMTd performance growth at year one. Interaction effects between ARB history and alcohol use frequency predicted attenuated PFMTd performance growth at years one and two. ARB history predicted attenuated RCFTi and RCFTd performance growth by year four, but not PCET or PLBT performance over time. By contrast, greater past-year alcohol use predicted attenuated PFMTi and PFMTd performance growth between years two and four in adolescents without an ARB history.ConclusionWe found that ARBs predict distinct, lasting changes in learning and memory for visual information, with results suggesting that the developing brain is vulnerable to ARBs during adolescence and emerging adulthood.

The factor structure of neuropsychological functioning among a large sample (N = 831) of American youth (ages 12-21 at baseline) was investigated in order to identify an optimal model. Candidate models were selected based on their potential to provide service to the study of adolescent development and the effects of heavy episodic alcohol consumption. Data on neuropsychological functioning were obtained from the NCANDA study. This is a longitudinal community study of the effects of alcohol exposure on neurodevelopment. Three conceptually motivated and one empirically motivated factor analysis model of neuropsychological domains were compared based on penalized-likelihood selection criteria and model fit statistics. Two conceptually-motivated models were found to have adequate fit and pattern invariance to function as a measurement model for the Penn Computerized Neurocognitive Battery (Penn CNB) anchored neuropsychological battery in NCANDA. Corroboration of previous factor analysis models was obtained, in addition to the identification of an alternative factor model that has higher discriminant capacity for neuropsychological domains hypothesized to be most sensitive to alcohol exposure in human adolescents. The findings support the use of a factor model developed originally for the Penn CNB and a model developed specifically for the NCANDA project. The NCANDA 8-Factor Model has conceptual and empirical advantages that were identified in the current and prior studies. These advantages are particularly valuable when applied in alcohol research settings.

The Adolescent Brain Cognitive Development (ABCD) Study of 11,880 youth incorporates a comprehensive range of measures assessing predictors and outcomes related to mental health across childhood and adolescence in participating youth, as well as information about family mental health history. We have previously described the logic and content of the mental health assessment battery at Baseline and 1-year follow-up. Here, we describe changes to that battery and issues and clarifications that have emerged, as well as additions to the mental health battery at the 2-, 3-, 4-, and 5-year follow-ups. We capitalize on the recent release of longitudinal data for caregiver and youth report of mental health data to evaluate trajectories of dimensions of psychopathology as a function of demographic factors. For both caregiver and self-reported mental health symptoms, males showed age-related decreases in internalizing and externalizing symptoms, while females showed an increase in internalizing symptoms with age. Multiple indicators of socioeconomic status (caregiver education, family income, financial adversity, neighborhood poverty) accounted for unique variance in both caregiver and youth-reported externalizing and internalizing symptoms. These data highlight the importance of examining developmental trajectories of mental health as a function of key factors such as sex and socioeconomic environment.

BackgroundDual systems theories suggest that greater imbalance between higher reward sensitivity and lower cognitive control across adolescence conveys risk for behaviors such as heavy episodic drinking (HED). Prior research demonstrated that psychological analogues of these systems, sensation seeking and premeditation, change from childhood through emerging adulthood, and each has been independently linked with HED. However, few studies have assessed whether change over time in these developing analogues is prospectively associated with HED. Moreover, we know of no research that has shown whether within-person differences between higher sensation seeking and relatively lower premeditation across the adolescent period predict HED in emerging adulthood.MethodsProspective data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study (n = 715) were used to examine the association of sensation seeking and premeditation with HED among adolescents ages 16 to 20 years. We used novel applications of latent difference score modeling and growth curve analysis to test whether increasing sensation seeking, premeditation, and their imbalance over time are associated with HED across the study period, and whether these associations differed by sex.ResultsWhereas premeditation increased linearly from adolescence through emerging adulthood across sexes, males reported growth and females reported decline in sensation seeking. Sensation seeking in adolescence (and not premeditation) was associated with higher levels of HED by emerging adulthood. Importantly, greater imbalance between sensation seeking and premeditation was associated with higher levels of HED by emerging adulthood though we note that variability capturing this imbalance correlated highly (r = 0.86) with baseline levels of sensation seeking.ConclusionsDevelopmental imbalance between higher sensation seeking and lower premeditation in late adolescence may be a risk factor for greater HED in emerging adulthood.

Exogenous causes, such as alcohol use, and endogenous factors, such as temperament and sex, can modulate developmental trajectories of adolescent neurofunctional maturation. We examined how these factors affect sexual dimorphism in brain functional networks in youth drinking below diagnostic threshold for alcohol use disorder (AUD). Based on the 3-year, annually acquired, longitudinal resting-state functional magnetic resonance imaging (MRI) data of 526 adolescents (12-21 years at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) cohort, developmental trajectories of 23 intrinsic functional networks (IFNs) were analyzed for (1) sexual dimorphism in 259 participants who were no-to-low drinkers throughout this period; (2) sex-alcohol interactions in two age- and sex-matched NCANDA subgroups (N = 76 each), half no-to-low, and half moderate-to-heavy drinkers; and (3) moderating effects of gender-specific alcohol dose effects and a multifactorial impulsivity measure on IFN connectivity in all NCANDA participants. Results showed that sex differences in no-to-low drinkers diminished with age in the inferior-occipital network, yet girls had weaker within-network connectivity than boys in six other networks. Effects of adolescent alcohol use were more pronounced in girls than boys in three IFNs. In particular, girls showed greater within-network connectivity in two motor networks with more alcohol consumption, and these effects were mediated by sensation-seeking only in girls. Our results implied that drinking might attenuate the naturally diminishing sexual differences by disrupting the maturation of network efficiency more severely in girls. The sex-alcohol-dose effect might explain why women are at higher risk of alcohol-related health and psychosocial consequences than men.

Physical health in childhood is crucial for neurobiological as well as overall development, and can shape long-term outcomes into adulthood. The landmark, longitudinal Adolescent Brain Cognitive Development StudySM (ABCD study®), was designed to investigate brain development and health in almost 12,000 youth who were recruited when they were 9-10 years old and will be followed through adolescence and early adulthood. The overall goal of this paper is to provide descriptive analyses of physical health measures in the ABCD study at baseline, including but not limited to sleep, physical activity and sports involvement, and body mass index. Further this summary will describe how physical health measures collected from the ABCD cohort compare with current normative data and clinical guidelines. We propose this data set has the potential to facilitate clinical recommendations and inform national standards of physical health in this age group. This manuscript will also provide important information for ABCD users and help guide analyses investigating physical health including new avenues for health disparity research as it pertains to adolescent and young adult development.

AimTo examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics.MethodsCross-sectional metrics of puberty were utilized from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study-a multi-site sample of 9-10 year-olds (n = 11,875)-and included perceived physical features via the pubertal development scale (PDS) and child salivary hormone levels (dehydroepiandrosterone and testosterone in all, and estradiol in females). Multi-level models examined the relationships among sociodemographic measures, physical features, and hormone levels. A group factor analysis (GFA) was implemented to extract latent variables of pubertal maturation that integrated both measures of perceived physical features and hormone levels.ResultsPDS summary scores indicated more males (70%) than females (31%) were prepubertal. Perceived physical features and hormone levels were significantly associated with child's weight status and income, such that more mature scores were observed among children that were overweight/obese or from households with low-income. Results from the GFA identified two latent factors that described individual differences in pubertal maturation among both females and males, with factor 1 driven by higher hormone levels, and factor 2 driven by perceived physical maturation. The correspondence between latent factor 1 scores (hormones) and latent factor 2 scores (perceived physical maturation) revealed synchronous and asynchronous relationships between hormones and concomitant physical features in this large young adolescent sample.ConclusionsSociodemographic measures were associated with both objective hormone and self-report physical measures of pubertal maturation in a large, diverse sample of 9-10 year-olds. The latent variables of pubertal maturation described a complex interplay between perceived physical changes and hormone levels that hallmark sexual maturation, which future studies can examine in relation to trajectories of brain maturation, risk/resilience to substance use, and other mental health outcomes.

Background: Life events experienced during adolescence are associated with risk and resilience to heavy episodic drinking (HED; i.e. binge drinking). The current study builds on prior research using latent class analysis (LCA) to examine heterogeneity in patterns of adolescent life events at baseline to HED over the course of three years (4 timepoints) as part of the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA). Methods: Life event classes were modeled using LCA that characterized NCANDA participants based upon their responses to the Life Events Questionnaire (N = 467, age: M = 14.98, SD = 1.69, 49.7% female). These baseline latent life event classes were then compared to HED at baseline and years 1, 2 and 3 using multinomial logistic regression. Results: At baseline, the LCA characterized four classes of adolescents based on endorsement of life events: negative-relational conflict (n = 65, 13.9%), negative-financial problems (n = 49, 10.5%), low life events (n = 130, 27.8%), and positive life events (n = 223, 47.8%). Life event trajectories differed for the negative life event classes compared to the other two classes, with greater odds of HED in the negative-financial problems class at year 1. Conclusion: The four latent classes derived from the life events of NCANDA youth yielded a characterization of adolescents that could aid in understanding HED over the subsequent three years, suggesting that everyday life events may inform adolescent binge drinking.

Purpose of studyApproximately two thirds of youth report experiencing or witnessing a trauma. It is not known whether trauma or the posttraumatic stress symptoms (PTSS) following trauma increases adolescent drinking risk.Recent findingsWe described trauma experienced by the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) longitudinal sample (N=831) participants and examined drinking over 4 years. We hypothesize that more traumatic events and PTSS will predict transition to moderate/heavy drinking.Summary658 no/low drinkers at baseline were followed yearly for 4 years for transition to moderate/heavy drinking using logistic regression models. Youth were grouped by: No Trauma (n=257), Trauma (n= 348), and Trauma with PTSS (n=53). Those with Trauma and PTSS showed escalation to moderate/heavy drinking compared to the No Trauma group in follow-up years 2, 3, and 4. Number of traumatic events did not predict moderate/heavy drinking. Interventions targeting PTSS may prevent transition to moderate/heavy drinking.

BackgroundThe cerebellum is a target of alcoholism-related brain damage in adults, yet no study has prospectively tracked deviations from normal cerebellar growth trajectories in adolescents before and after initiating drinking.MethodsMagnetic resonance imaging tracked developmental volume trajectories of 10 cerebellar lobule and vermis tissue constituents in 548 no/low drinking youths age 12 to 21 years at induction into this 5-site, NCANDA (National Consortium on Alcohol and NeuroDevelopment in Adolescence) study. Over the 3- to 4-year longitudinal examination yielding 2043 magnetic resonance imaging scans, 328 youths remained no/low drinkers, whereas 220 initiated substantial drinking after initial neuroimaging.ResultsNormal growth trajectories derived from no/low drinkers indicated that gray matter volumes of lobules V and VI, crus II, lobule VIIB, and lobule X declined faster with age in male youths than in female youths, whereas white matter volumes in crus I and crus II and lobules VIIIA and VIIIB expanded faster in female youths than in male youths; cerebrospinal fluid volume expanded faster in most cerebellar regions of male youths than female youths. Drinkers exhibited accelerated gray matter decline in anterior lobules and vermis, accelerated vermian white matter expansion, and accelerated cerebrospinal fluid volumes expansion of anterior lobules relative to youths who remained no/low drinkers. Analyses including both alcohol and marijuana did not support an independent role for marijuana in alcohol effects on cerebellar gray matter trajectories.ConclusionsAlcohol use-related cerebellar growth trajectory differences from normal involved anterior lobules and vermis of youths who initiated substantial drinking. These regions are commonly affected in alcohol-dependent adults, raising the possibility that cerebellar structures affected by youthful drinking may be vulnerable to age-alcohol interactions in later adulthood.

AimTo examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics.MethodsCross-sectional metrics of puberty were utilized from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study-a multi-site sample of 9-10 year-olds (n = 11,875)-and included perceived physical features via the pubertal development scale (PDS) and child salivary hormone levels (dehydroepiandrosterone and testosterone in all, and estradiol in females). Multi-level models examined the relationships among sociodemographic measures, physical features, and hormone levels. A group factor analysis (GFA) was implemented to extract latent variables of pubertal maturation that integrated both measures of perceived physical features and hormone levels.ResultsPDS summary scores indicated more males (70%) than females (31%) were prepubertal. Perceived physical features and hormone levels were significantly associated with child's weight status and income, such that more mature scores were observed among children that were overweight/obese or from households with low-income. Results from the GFA identified two latent factors that described individual differences in pubertal maturation among both females and males, with factor 1 driven by higher hormone levels, and factor 2 driven by perceived physical maturation. The correspondence between latent factor 1 scores (hormones) and latent factor 2 scores (perceived physical maturation) revealed synchronous and asynchronous relationships between hormones and concomitant physical features in this large young adolescent sample.ConclusionsSociodemographic measures were associated with both objective hormone and self-report physical measures of pubertal maturation in a large, diverse sample of 9-10 year-olds. The latent variables of pubertal maturation described a complex interplay between perceived physical changes and hormone levels that hallmark sexual maturation, which future studies can examine in relation to trajectories of brain maturation, risk/resilience to substance use, and other mental health outcomes.

The Adolescent Brain and Cognitive Development (ABCD) Study incorporates a comprehensive range of measures assessing predictors and outcomes related to both mental and physical health across childhood and adolescence. The workgroup developed a battery that would assess a comprehensive range of domains that address study aims while minimizing participant and family burden. We review the major considerations that went into deciding what constructs to cover in the demographics, physical health and mental health domains, as well as the process of selecting measures, piloting and refining the originally proposed battery. We present a description of the baseline battery, as well as the six-month interim assessments and the one-year follow-up assessments. This battery includes assessments from the perspectives of both the parent and the target youth, as well as teacher reports. This battery will provide a foundational baseline assessment of the youth's current function so as to permit characterization of stability and change in key domains over time. The findings from this battery will also be utilized to identify both resilience markers that predict healthy development and risk factors for later adverse outcomes in physical health, mental health, and substance use and abuse.

Observational neuroimaging studies with children and adolescents may identify neurological anomalies and other clinically relevant findings. Planning for the management of this information involves ethical considerations that may influence informed consent, confidentiality, and communication with participants about assessment results. Biomedical ethics principles include respect for autonomy, beneficence, non-maleficence, and justice. Each project presents unique challenges. The Adolescent Brain and Cognitive Development study (ABCD) collaborators have systematically developed recommendations with written guidelines for identifying and responding to potential risks that adhere to biomedical ethics principles. To illustrate, we will review the ABCD approach to three areas: (1) hazardous substance use; (2) neurological anomalies; and (3) imminent potential for self-harm or harm to others. Each ABCD site is responsible for implementing procedures consistent with these guidelines in accordance with their Institutional Review Board approved protocols, state regulations, and local resources. To assure that each site has related plans and resources in place, site emergency procedures manuals have been developed, documented and reviewed for adherence to ABCD guidelines. This article will describe the principles and process used to develop these ABCD bioethics and medical oversight guidelines, the concerns and options considered, and the resulting approaches advised to sites.

ObjectiveThe authors sought evidence for altered adolescent brain growth trajectory associated with moderate and heavy alcohol use in a large national, multisite, prospective study of adolescents before and after initiation of appreciable alcohol use.MethodThis study examined 483 adolescents (ages 12-21) before initiation of drinking and 1 and 2 years later. At the 2-year assessment, 356 participants continued to meet the study's no/low alcohol consumption entry criteria, 65 had initiated moderate drinking, and 62 had initiated heavy drinking. MRI was used to quantify regional cortical and white matter volumes. Percent change per year (slopes) in adolescents who continued to meet no/low criteria served as developmental control trajectories against which to compare those who initiated moderate or heavy drinking.ResultsIn no/low drinkers, gray matter volume declined throughout adolescence and slowed in many regions in later adolescence. Complementing gray matter declines, white matter regions grew at faster rates at younger ages and slowed toward young adulthood. Youths who initiated heavy drinking exhibited an accelerated frontal cortical gray matter trajectory, divergent from the norm. Although significant effects on trajectories were not observed in moderate drinkers, their intermediate position between no/low and heavy drinkers suggests a dose effect. Neither marijuana co-use nor baseline volumes contributed significantly to the alcohol effect.ConclusionsInitiation of drinking during adolescence, with or without marijuana co-use, disordered normal brain growth trajectories. Factors possibly contributing to abnormal cortical volume trajectories include peak consumption in the past year and family history of alcoholism.

The transition from adolescent to adult cognition and emotional control requires neurodevelopmental maturation likely involving intrinsic functional networks (IFNs). Normal neurodevelopment may be vulnerable to disruption from environmental insult such as alcohol consumption commonly initiated during adolescence. To test potential disruption to IFN maturation, we used resting-state functional magnetic resonance imaging (rs-fMRI) in 581 no-to-low alcohol-consuming and 117 moderate-to-high-drinking youth. Functional seed-to-voxel connectivity analysis assessed age, sex, and moderate alcohol drinking on default-mode, executive-control, salience, reward, and emotion networks and tested cognitive and motor coordination correlates of network connectivity. Among no-to-low alcohol-consuming adolescents, executive-control frontolimbicstriatal connectivity was stronger in older than younger adolescents, particularly boys, and predicted better ability in balance, memory, and impulse control. Connectivity patterns in moderate-to-high-drinking youth were tested mainly in late adolescence when drinking was initiated. Implicated was the emotion network with attenuated connectivity to default-mode network regions. Our cross-sectional rs-fMRI findings from this large cohort of adolescents show sexual dimorphism in connectivity and suggest neurodevelopmental rewiring toward stronger and spatially more distributed executive-control networking in older than younger adolescents. Functional network rewiring in moderate-to-high-drinking adolescents may impede maturation of affective and self-reflection systems and obscure maturation of complex social and emotional behaviors.

Structural MRI of volunteers deemed "normal" following clinical interview provides a window into normal brain developmental morphology but also reveals unexpected dysmorphology, commonly known as "incidental findings." Although unanticipated, these anatomical findings raise questions regarding possible treatment that could even ultimately require neurosurgical intervention, which itself carries significant risk but may not be indicated if the anomaly is nonprogressive or of no functional consequence. Neuroradiological readings of 833 structural MRI from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) cohort found an 11.8 % incidence of brain structural anomalies, represented proportionately across the five collection sites and ethnic groups. Anomalies included 26 mega cisterna magna, 15 subarachnoid cysts, 12 pineal cysts, 12 white matter dysmorphologies, 5 tonsillar ectopias, 5 prominent perivascular spaces, 5 gray matter heterotopias, 4 pituitary masses, 4 excessively large or asymmetrical ventricles, 4 cavum septum pellucidum, 3 developmental venous anomalies, 1 exceptionally large midsagittal vein, and single cases requiring clinical followup: cranio-cervical junction stenosis, parietal cortical mass, and Chiari I malformation. A case of possible demyelinating disorder (e.g., neuromyelitis optica or multiple sclerosis) newly emerged at the 1-year NCANDA followup, requiring clinical referral. Comparing test performance of the 98 anomalous cases with 619 anomaly-free no-to-low alcohol consuming adolescents revealed significantly lower scores on speed measures of attention and motor functions; these differences were not attributed to any one anomaly subgroup. Further, we devised an automated approach for quantifying posterior fossa CSF volumes for detection of mega cisterna magna, which represented 26.5 % of clinically identified anomalies. Automated quantification fit a Gaussian distribution with a rightward skew. Using a 3SD cut-off, quantification identified 22 of the 26 clinically-identified cases, indicating that cases with percent of CSF in the posterior-inferior-middle aspect of the posterior fossa ≥3SD merit further review, and support complementing clinical readings with objective quantitative analysis. Discovery of asymptomatic brain structural anomalies, even when no clinical action is indicated, can be disconcerting to the individual and responsible family members, raising a disclosure dilemma: refrain from relating the incidental findings to avoid unnecessary alarm or anxiety; or alternatively, relate the neuroradiological findings as "normal variants" to the study volunteers and family, thereby equipping them with knowledge for the future should they have the occasion for a brain scan following an illness or accident that the incidental findings predated the later event.

BackgroundAbundant cross-sectional evidence links eveningness (a preference for later sleep-wake timing) and increased alcohol and drug use among adolescents and young adults. However, longitudinal studies are needed to examine whether eveningness is a risk factor for subsequent alcohol and drug use, particularly during adolescence, which is marked by parallel peaks in eveningness and risk for the onset of alcohol use disorders. This study examined whether eveningness and other sleep characteristics were associated with concurrent or subsequent substance involvement in a longitudinal study of adolescents.MethodsParticipants were 729 adolescents (368 females; age 12 to 21 years) in the National Consortium on Alcohol and Neurodevelopment in Adolescence study. Associations between the sleep variables (circadian preference, sleep quality, daytime sleepiness, sleep timing, and sleep duration) and 3 categorical substance variables (at-risk alcohol use, alcohol bingeing, and past-year marijuana use [y/n]) were examined using ordinal and logistic regression with baseline age, sex, race, ethnicity, socioeconomic status, and psychiatric problems as covariates.ResultsAt baseline, greater eveningness was associated with greater at-risk alcohol use, greater bingeing, and past-year use of marijuana. Later weekday and weekend bedtimes, but not weekday or weekend sleep duration, showed similar associations across the 3 substance outcomes at baseline. Greater baseline eveningness was also prospectively associated with greater bingeing and past-year use of marijuana at the 1-year follow-up, after covarying for baseline bingeing and marijuana use. Later baseline weekday and weekend bedtimes, and shorter baseline weekday sleep duration, were similarly associated with greater bingeing and past-year use of marijuana at the 1-year follow-up after covarying for baseline values.ConclusionsFindings suggest that eveningness and sleep timing may be under recognized risk factors and future areas of intervention for adolescent involvement in alcohol and marijuana that should be considered along with other previously identified sleep factors such as insomnia and insufficient sleep.

Longitudinal study provides a robust method for tracking developmental trajectories. Yet inherent problems of retesting pose challenges in distinguishing biological developmental change from prior testing experience. We examined factors potentially influencing change scores on 16 neuropsychological test composites over 1year in 568 adolescents in the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) project. The twice-minus-once-tested method revealed that performance gain was mainly attributable to testing experience (practice) with little contribution from predicted developmental effects. Group mean practice slopes for 13 composites indicated that 60% to ∼100% variance was attributable to test experience; General Ability accuracy showed the least practice effect (29%). Lower baseline performance, especially in younger participants, was a strong predictor of greater gain. Contributions from age, sex, ethnicity, examination site, socioeconomic status, or family history of alcohol/substance abuse were nil to small, even where statistically significant. Recognizing that a substantial proportion of change in longitudinal testing, even over 1-year, is attributable to testing experience indicates caution against assuming that performance gain observed during periods of maturation necessarily reflects development. Estimates of testing experience, a form of learning, may be a relevant metric for detecting interim influences, such as alcohol use or traumatic episodes, on behavior.

During adolescence, problems reflecting cognitive, behavioral and affective dysregulation, such as inattention and emotional dyscontrol, have been observed to be associated with substance use disorder (SUD) risks and outcomes. Prior studies have typically been with small samples, and have typically not included comprehensive measurement of executive dysfunction domains. The relationships of executive dysfunction in daily life with performance based testing of cognitive skills and structural brain characteristics, thought to be the basis for executive functioning, have not been definitively determined. The aims of this study were to determine the relationships between executive dysfunction in daily life, measured by the Behavior Rating Inventory of Executive Function (BRIEF), cognitive skills and structural brain characteristics, and SUD risks, including a global SUD risk indicator, sleep quality, and risky alcohol and cannabis use. In addition to bivariate relationships, multivariate models were tested. The subjects (n = 817; ages 12 through 21) were participants in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study. The results indicated that executive dysfunction was significantly related to SUD risks, poor sleep quality, risky alcohol use and cannabis use, and was not significantly related to cognitive skills or structural brain characteristics. In multivariate models, the relationship between poor sleep quality and risky substance use was mediated by executive dysfunction. While these cross-sectional relationships need to be further examined in longitudinal analyses, the results suggest that poor sleep quality and executive dysfunction may be viable preventive intervention targets to reduce adolescent substance use.

UnlabelledReports an error in "Cognitive, emotion control, and motor performance of adolescents in the NCANDA study: Contributions from alcohol consumption, age, sex, ethnicity, and family history of addiction" by Edith V. Sullivan, Ty Brumback, Susan F. Tapert, Rosemary Fama, Devin Prouty, Sandra A. Brown, Kevin Cummins, Wesley K. Thompson, Ian M. Colrain, Fiona C. Baker, Michael D. De Bellis, Stephen R. Hooper, Duncan B. Clark, Tammy Chung, Bonnie J. Nagel, B. Nolan Nichols, Torsten Rohlfing, Weiwei Chu, Kilian M. Pohl and Adolf Pfefferbaum (Neuropsychology, 2016[May], Vol 30[4], 449-473). A problem with a computation to invert speed scores is noted and explained in this correction. All statements indicating group differences in speed scores, as well as Table 5 and Figure 8A, have been corrected in the online version of this article. (The following abstract of the original article appeared in record 2016-00613-001.)ObjectiveTo investigate development of cognitive and motor functions in healthy adolescents and to explore whether hazardous drinking affects the normal developmental course of those functions.MethodParticipants were 831 adolescents recruited across 5 United States sites of the National Consortium on Alcohol and NeuroDevelopment in Adolescence 692 met criteria for no/low alcohol exposure, and 139 exceeded drinking thresholds. Cross-sectional, baseline data were collected with computerized and traditional neuropsychological tests assessing 8 functional domains expressed as composite scores. General additive modeling evaluated factors potentially modulating performance (age, sex, ethnicity, socioeconomic status, and pubertal developmental stage).ResultsOlder no/low-drinking participants achieved better scores than younger ones on 5 accuracy composites (general ability, abstraction, attention, emotion, and balance). Speeded responses for attention, motor speed, and general ability were sensitive to age and pubertal development. The exceeds-threshold group (accounting for age, sex, and other demographic factors) performed significantly below the no/low-drinking group on balance accuracy and on general ability, attention, episodic memory, emotion, and motor speed scores and showed evidence for faster speed at the expense of accuracy. Delay Discounting performance was consistent with poor impulse control in the younger no/low drinkers and in exceeds-threshold drinkers regardless of age.ConclusionsHigher achievement with older age and pubertal stage in general ability, abstraction, attention, emotion, and balance suggests continued functional development through adolescence, possibly supported by concurrently maturing frontal, limbic, and cerebellar brain systems. Determination of whether low scores by the exceeds-threshold group resulted from drinking or from other preexisting factors requires longitudinal study.

Brain structural development continues throughout adolescence, when experimentation with alcohol is often initiated. To parse contributions from biological and environmental factors on neurodevelopment, this study used baseline National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) magnetic resonance imaging (MRI) data, acquired in 674 adolescents meeting no/low alcohol or drug use criteria and 134 adolescents exceeding criteria. Spatial integrity of images across the 5 recruitment sites was assured by morphological scaling using Alzheimer's disease neuroimaging initiative phantom-derived volume scalar metrics. Clinical MRI readings identified structural anomalies in 11.4%. Cortical volume and thickness were smaller and white matter volumes were larger in older than in younger adolescents. Effects of sex (male > female) and ethnicity (majority > minority) were significant for volume and surface but minimal for cortical thickness. Adjusting volume and area for supratentorial volume attenuated or removed sex and ethnicity effects. That cortical thickness showed age-related decline and was unrelated to supratentorial volume is consistent with the radial unit hypothesis, suggesting a universal neural development characteristic robust to sex and ethnicity. Comparison of NCANDA with PING data revealed similar but flatter, age-related declines in cortical volumes and thickness. Smaller, thinner frontal, and temporal cortices in the exceeds-criteria than no/low-drinking group suggested untoward effects of excessive alcohol consumption on brain structural development.

UnlabelledReports an error in "Cognitive, emotion control, and motor performance of adolescents in the NCANDA study: Contributions from alcohol consumption, age, sex, ethnicity, and family history of addiction" by Edith V. Sullivan, Ty Brumback, Susan F. Tapert, Rosemary Fama, Devin Prouty, Sandra A. Brown, Kevin Cummins, Wesley K. Thompson, Ian M. Colrain, Fiona C. Baker, Michael D. De Bellis, Stephen R. Hooper, Duncan B. Clark, Tammy Chung, Bonnie J. Nagel, B. Nolan Nichols, Torsten Rohlfing, Weiwei Chu, Kilian M. Pohl and Adolf Pfefferbaum (Neuropsychology, 2016[May], Vol 30[4], 449-473). A problem with a computation to invert speed scores is noted and explained in this correction. All statements indicating group differences in speed scores, as well as Table 5 and Figure 8A, have been corrected in the online version of this article. (The following abstract of the original article appeared in record 2016-00613-001.)ObjectiveTo investigate development of cognitive and motor functions in healthy adolescents and to explore whether hazardous drinking affects the normal developmental course of those functions.MethodParticipants were 831 adolescents recruited across 5 United States sites of the National Consortium on Alcohol and NeuroDevelopment in Adolescence 692 met criteria for no/low alcohol exposure, and 139 exceeded drinking thresholds. Cross-sectional, baseline data were collected with computerized and traditional neuropsychological tests assessing 8 functional domains expressed as composite scores. General additive modeling evaluated factors potentially modulating performance (age, sex, ethnicity, socioeconomic status, and pubertal developmental stage).ResultsOlder no/low-drinking participants achieved better scores than younger ones on 5 accuracy composites (general ability, abstraction, attention, emotion, and balance). Speeded responses for attention, motor speed, and general ability were sensitive to age and pubertal development. The exceeds-threshold group (accounting for age, sex, and other demographic factors) performed significantly below the no/low-drinking group on balance accuracy and on general ability, attention, episodic memory, emotion, and motor speed scores and showed evidence for faster speed at the expense of accuracy. Delay Discounting performance was consistent with poor impulse control in the younger no/low drinkers and in exceeds-threshold drinkers regardless of age.ConclusionsHigher achievement with older age and pubertal stage in general ability, abstraction, attention, emotion, and balance suggests continued functional development through adolescence, possibly supported by concurrently maturing frontal, limbic, and cerebellar brain systems. Determination of whether low scores by the exceeds-threshold group resulted from drinking or from other preexisting factors requires longitudinal study.

Neurodevelopment continues through adolescence, with notable maturation of white matter tracts comprising regional fiber systems progressing at different rates. To identify factors that could contribute to regional differences in white matter microstructure development, large samples of youth spanning adolescence to young adulthood are essential to parse these factors. Recruitment of adequate samples generally relies on multi-site consortia but comes with the challenge of merging data acquired on different platforms. In the current study, diffusion tensor imaging (DTI) data were acquired on GE and Siemens systems through the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a multi-site study designed to track the trajectories of regional brain development during a time of high risk for initiating alcohol consumption. This cross-sectional analysis reports baseline Tract-Based Spatial Statistic (TBSS) of regional fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (L1), and radial diffusivity (LT) from the five consortium sites on 671 adolescents who met no/low alcohol or drug consumption criteria and 132 adolescents with a history of exceeding consumption criteria. Harmonization of DTI metrics across manufacturers entailed the use of human-phantom data, acquired multiple times on each of three non-NCANDA participants at each site's MR system, to determine a manufacturer-specific correction factor. Application of the correction factor derived from human phantom data measured on MR systems from different manufacturers reduced the standard deviation of the DTI metrics for FA by almost a half, enabling harmonization of data that would have otherwise carried systematic error. Permutation testing supported the hypothesis of higher FA and lower diffusivity measures in older adolescents and indicated that, overall, the FA, MD, and L1 of the boys were higher than those of the girls, suggesting continued microstructural development notable in the boys. The contribution of demographic and clinical differences to DTI metrics was assessed with General Additive Models (GAM) testing for age, sex, and ethnicity differences in regional skeleton mean values. The results supported the primary study hypothesis that FA skeleton mean values in the no/low-drinking group were highest at different ages. When differences in intracranial volume were covaried, FA skeleton mean reached a maximum at younger ages in girls than boys and varied in magnitude with ethnicity. Our results, however, did not support the hypothesis that youth who exceeded exposure criteria would have lower FA or higher diffusivity measures than the no/low-drinking group; detecting the effects of excessive alcohol consumption during adolescence on DTI metrics may require longitudinal study.

ObjectiveDuring adolescence, neurobiological maturation occurs concurrently with social and interpersonal changes, including the initiation of alcohol and other substance use. The National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) is designed to disentangle the complex relationships between onset, escalation, and desistance of alcohol use and changes in neurocognitive functioning and neuromaturation.MethodA sample of 831 youth, ages 12-21 years, was recruited at five sites across the United States, oversampling those at risk for alcohol use problems. Most (83%) had limited or no history of alcohol or other drug use, and a smaller portion (17%) exceeded drinking thresholds. A comprehensive assessment of biological development, family background, psychiatric symptomatology, and neuropsychological functioning-in addition to anatomical, diffusion, and functional brain magnetic resonance imaging-was completed at baseline.ResultsThe NCANDA sample of youth is nationally representative of sex and racial/ethnic groups. More than 50% have at least one risk characteristic for subsequent heavy drinking (e.g., family history, internalizing or externalizing symptoms). As expected, those who exceeded drinking thresholds (n = 139) differ from those who did not (n = 692) on identified factors associated with early alcohol use and problems.ConclusionsNCANDA successfully recruited a large sample of adolescents and comprehensively assessed psychosocial functioning across multiple domains. Based on the sample's risk profile, NCANDA is well positioned to capture the transition into drinking and alcohol problems in a large portion of the cohort, as well as to help disentangle the associations between alcohol use, neurobiological maturation, and neurocognitive development and functioning.

ObjectivesTo determine protease mutations that develop at viral failure for protease inhibitor (PI)-naive patients on a regimen containing the PI atazanavir.MethodsResistance tests on patients failing atazanavir, conducted as part of routine clinical care in a multicentre observational study, were randomly matched by subtype to resistance tests from PI-naive controls to account for natural polymorphisms. Mutations from the consensus B sequence across the protease region were analysed for association and defined using the IAS-USA 2011 classification list.ResultsFour hundred and five of 2528 (16%) patients failed therapy containing atazanavir as a first PI over a median (IQR) follow-up of 1.76 (0.84-3.15) years and 322 resistance tests were available for analysis. Recognized major atazanavir mutations were found in six atazanavir-experienced patients (P < 0.001), including I50L and N88S. The minor mutations most strongly associated with atazanavir experience were M36I, M46I, F53L, A71V, V82T and I85V (P < 0.05). Multiple novel mutations, I15S, L19T, K43T, L63P/V, K70Q, V77I and L89I/T/V, were also associated with atazanavir experience.ConclusionsViral failure on atazanavir-containing regimens was not common and major resistance mutations were rare, suggesting that adherence may be a major contributor to viral failure. Novel mutations were described that have not been previously documented.