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Background and Aims: Recently, 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 Setting: Cross-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)., Cases: Cases 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., Measurements: Graph theory metrics of segregation and integration were used to summarize SCN., Findings: Mirroring 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., Conclusion: Structural 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., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

This article is part of a Festschrift commemorating the 50th anniversary of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Established in 1970, first as part of the National Institute of Mental Health and later as an independent institute of the National Institutes of Health, NIAAA today is the world's largest funding agency for alcohol research. In addition to its own intramural research program, NIAAA supports the entire spectrum of innovative basic, translational, and clinical research to advance the diagnosis, prevention, and treatment of alcohol use disorder and alcohol-related problems. To celebrate the anniversary, NIAAA hosted a 2-day symposium, "Alcohol Across the Lifespan: 50 Years of Evidence-Based Diagnosis, Prevention, and Treatment Research," devoted to key topics within the field of alcohol research. This article is based on Dr. Tapert's presentation at the event. NIAAA Director George F. Koob, Ph.D., serves as editor of the Festschrift., Competing Interests: Disclosures The authors declare no competing financial or nonfinancial interests.

Background: Substance use research has focused on family history of alcohol use disorders but less on other addictions in biological family members. We examined how parental substance use history relates to reward system functioning, specifically nucleus accumbens (NAcc) and putamen activation at age 9-10 in the Adolescent Brain Cognitive Development (ABCD) Study. This research hopes to address limitations in prior literature by focusing analyses on a large, substance-naïve sample., Method: We included ABCD participants with valid Monetary Incentive Delay task fMRI Baseline data and parent substance use history at project baseline from Data Release 2.0 (N = 10,622). Parent-history-positive (PH+) participants had one or both biological parents with a history of two+problems with alcohol (n = 741; PH+A) and/or other drugs (n = 638; PH+D). Of participants who were parent-history-negative (PH-) for alcohol and/or drugs, a stratified random sample based on six sociodemographic variables was created and matched to the PH+group (PH-A n = 699; PH-D n = 615). The contrast of interest was anticipation of a large reward vs. neutral response., Results: PH+A youth had more activation in the right NAcc during large reward anticipation than PH-A. PH+D youth showed enhanced left putamen activation during large reward anticipation than PH-D youth. Bayesian hypothesis testing showed moderate evidence (BF > 3) in favor of the null hypothesis., Conclusion: These findings suggest that pre-adolescents whose biological parents had a history of substance-related problems show small differences in reward processing compared to their PH- peers., (Published by Elsevier Ltd.)

Importance: Maturation of white matter fiber systems subserves cognitive, behavioral, emotional, and motor development during adolescence. Hazardous drinking during this active neurodevelopmental period may alter the trajectory of white matter microstructural development, potentially increasing risk for developing alcohol-related dysfunction and alcohol use disorder in adulthood., Objective: To identify disrupted adolescent microstructural brain development linked to drinking onset and to assess whether the disruption is more pronounced in younger rather than older adolescents., Design, Setting, and Participants: This case-control study, conducted from January 13, 2013, to January 15, 2019, consisted of an analysis of 451 participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence cohort. Participants were aged 12 to 21 years at baseline and had at least 2 usable magnetic resonance diffusion tensor imaging (DTI) scans and up to 5 examination visits spanning 4 years. Participants with a youth-adjusted Cahalan score of 0 were labeled as no-to-low drinkers; those with a score of greater than 1 for at least 2 consecutive visits were labeled as heavy drinkers. Exploratory analysis was conducted between no-to-low and heavy drinkers. A between-group analysis was conducted between age- and sex-matched youths, and a within-participant analysis was performed before and after drinking., Exposures: Self-reported alcohol consumption in the past year summarized by categorical drinking levels., Main Outcomes and Measures: Diffusion tensor imaging measurement of fractional anisotropy (FA) in the whole brain and fiber systems quantifying the developmental change of each participant as a slope., Results: Analysis of whole-brain FA of 451 adolescents included 291 (64.5%) no-to-low drinkers and 160 (35.5%) heavy drinkers who indicated the potential for a deleterious association of alcohol with microstructural development. Among the no-to-low drinkers, 142 (48.4%) were boys with mean (SD) age of 16.5 (2.2) years and 149 (51.2%) were girls with mean (SD) age of 16.5 (2.1) years and 192 (66.0%) were White participants. Among the heavy drinkers, 86 (53.8%) were boys with mean (SD) age of 20.1 (1.5) years and 74 (46.3%) were girls with mean (SD) age of 20.5 (2.0) years and 142 (88.8%) were White participants. A group analysis revealed FA reduction in heavy-drinking youth compared with age- and sex-matched controls (t154 = -2.7, P = .008). The slope of this reduction correlated with log of days of drinking since the baseline visit (r156 = -0.21, 2-tailed P = .008). A within-participant analysis contrasting developmental trajectories of youths before and after they initiated heavy drinking supported the prediction that drinking onset was associated with and potentially preceded disrupted white matter integrity. Age-alcohol interactions (t152 = 3.0, P = .004) observed for the FA slopes indicated that the alcohol-associated disruption was greater in younger than older adolescents and was most pronounced in the genu and body of the corpus callosum, regions known to continue developing throughout adolescence., Conclusions and Relevance: This case-control study of adolescents found a deleterious association of alcohol use with white matter microstructural integrity. These findings support the concept of heightened vulnerability to environmental agents, including alcohol, associated with attenuated development of major white matter tracts in early adolescence.

Background: Childhood trauma is known to impart risk for several adverse life outcomes. Yet, its impact during adolescent development is not well understood. We aimed to investigate the relationships among childhood trauma, functional brain connectivity, executive dysfunction (ED), and the development of high-risk drinking in adolescence., Methods: Data from the National Consortium on Alcohol and Neurodevelopment in Adolescence (sample size = 392, 55% female) cohort were used. This included resting-state functional magnetic resonance imaging at baseline, childhood trauma and ED self-reports, and detailed interviews on alcohol and substance use collected at baseline and at 4 annual follow-ups. We used longitudinal regression analyses to confirm the relationship between childhood trauma and ED, identified the mediating functional brain network hubs, and used these linkages to predict future high-risk drinking in adolescence., Results: Childhood trauma severity was significantly related to ED in all years. At baseline, distributed functional connectivity from hub regions in the bilateral dorsal anterior cingulate cortex, right anterior insula, right intraparietal sulcus, and bilateral pre- and postcentral gyri mediated the relationship between childhood trauma and ED. Furthermore, high-risk drinking in follow-up years 1-4 could be predicted with high accuracy from the trauma-affected functional brain networks that mediated ED at baseline, together with age, childhood trauma severity, and extent of ED., Discussion: Functional brain networks, particularly from hub regions important for cognitive and sensorimotor control, explain the relationship between childhood trauma and ED and are important for predicting future high-risk drinking. These findings are relevant for the prognosis of alcohol use disorders., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Acute alcohol consumption is associated with temporarily increased regional cerebral blood flow (CBF). The extent of this increase appears to be moderated by individual differences in the level of response (LR) to alcohol's subjective effects. The low LR phenotype is a known risk factor for the development of alcohol problems. This study investigates how the low LR phenotype relates to the relationship between alcohol-related changes in CBF and alcohol problems 5 years later., Methods: Young adults (ages 18 to 25) were selected based on their LR to alcohol and underwent a neuroimaging protocol including arterial spin labeling and functional scans. These participants were recontacted ~5 years later and assessed on alcohol outcomes. A final sample of 107 subjects (54 low and 53 high LR subjects) was included in the analyses. Whole-brain analysis revealed 5 clusters of significant alcohol-induced, versus placebo-induced, CBF changes that were consistent with a previous report. Peak alcohol-placebo CBF response was extracted from these regions and, along with the LR group, submitted to a hierarchical linear regression predicting alcohol problems. Analyses controlled for age, sex, and baseline alcohol problems., Results: In the regression analysis, greater alcohol-placebo CBF difference in the right middle/superior/inferior frontal gyri and bilateral anterior cingulate gyri clusters predicted greater future alcohol problems for the low LR group, whereas this relationship was not found to be significant in the high LR group., Conclusions: This study demonstrates a clinically important relationship between CBF and future alcohol problems, particularly in individuals with a low LR phenotype. These initial results help to elucidate the neurobiological pathways involved in the development of alcohol use disorders for individuals with low LR., (© 2019 by the Research Society on Alcoholism.)

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., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Underage drinking is widely recognized as a leading public health and social problem for adolescents in the United States. Being able to identify at-risk adolescents before they initiate heavy alcohol use could have important clinical and public health implications; however, few investigations have explored individual-level precursors of adolescent substance use. This prospective investigation used machine learning with demographic, neurocognitive, and neuroimaging data in substance-naive adolescents to identify predictors of alcohol use initiation by age 18., Method: Participants (N=137) were healthy substance-naive adolescents (ages 12-14) who underwent neuropsychological testing and structural and functional magnetic resonance imaging (sMRI and fMRI), and then were followed annually. By age 18, 70 youths (51%) initiated moderate to heavy alcohol use, and 67 remained nonusers. Random forest classification models identified the most important predictors of alcohol use from a large set of demographic, neuropsychological, sMRI, and fMRI variables., Results: Random forest models identified 34 predictors contributing to alcohol use by age 18, including several demographic and behavioral factors (being male, higher socioeconomic status, early dating, more externalizing behaviors, positive alcohol expectancies), worse executive functioning, and thinner cortices and less brain activation in diffusely distributed regions of the brain., Conclusions: Incorporating a mix of demographic, behavioral, neuropsychological, and neuroimaging data may be the best strategy for identifying youths at risk for initiating alcohol use during adolescence. The identified risk factors will be useful for alcohol prevention efforts and in research to address brain mechanisms that may contribute to early drinking.

Background: Low levels of alcohol responses (low LRs) are genetically influenced phenotypes that are identified before alcohol dependence and predict future heavy drinking and alcohol problems. A recent paper described 13 LR-related blood oxygen level-dependent (BOLD) response contrast patterns observed during an emotional face recognition task that might reflect cognitive processes contributing to LR and that might themselves predict adverse alcohol outcomes (Paulus et al., Biol Psychiatry 2012; 72: 848). This paper evaluates the predictive implications of those functional magnetic resonance imaging (fMRI) patterns., Methods: Of 120 subjects from Paulus and colleagues (2012), 114 (57 low and high LRs; ~50% females) were interviewed 5 years later at age 25. Correlations between baseline fMRI patterns and alcohol-related outcomes were evaluated, and regression analyses were used to determine if BOLD response contrasts incremented over LR in predicting outcomes., Results: Baseline fMRI patterns in 5 of 13 baseline regions of interest correlated with adverse outcomes. Such patterns in insular regions, particularly the left anterior insula, and the right frontal gyrus, added to LR in predicting alcohol problems. The relationships remained robust when exact binomial procedures were used, but, reflecting the small sample size, it was not possible to adequately consider Bonferroni corrections., Conclusions: The data suggest that fMRI BOLD response contrasts predicted heavier drinking and alcohol problems 5 years later, even after considering baseline low LRs. Future work will focus on whether fMRI results can predict outcomes in larger samples and among young nondrinkers, as well as how the imaging results increase understanding of the processes through which LR operates., (Copyright © 2016 by the Research Society on Alcoholism.)

Studies suggest marijuana impacts gray and white matter neural tissue development, however few prospective studies have determined the relationship between cortical thickness and cannabis use spanning adolescence to young adulthood. This study aimed to understand how heavy marijuana use influences cortical thickness trajectories across adolescence. Subjects were adolescents with heavy marijuana use and concomitant alcohol use (MJ+ALC, n=30) and controls (CON, n=38) with limited substance use histories. Participants underwent magnetic resonance imaging and comprehensive substance use assessment at three independent time points. Repeated measures analysis of covariance was used to look at main effects of group, time, and Group × Time interactions on cortical thickness. MJ+ALC showed thicker cortical estimates across the brain (23 regions), particularly in frontal and parietal lobes (ps<.05). More cumulative marijuana use was associated with increased thickness estimates by 3-year follow-up (ps<.05). Heavy marijuana use during adolescence and into young adulthood may be associated with altered neural tissue development and interference with neuromaturation that can have neurobehavioral consequences. Continued follow-up of adolescent marijuana users will help understand ongoing neural changes that are associated with development of problematic use into adulthood, as well as potential for neural recovery with cessation of use., (Published by Elsevier Ltd.)

Objective: Adolescent marijuana use continues to increase in prevalence as harm perception declines. Better understanding of marijuana's impact on neurodevelopment is crucial. This prospective study aimed to investigate cortical thickness and neurocognitive performance before and after 28 days of monitored abstinence in adolescent marijuana and alcohol users., Method: Subjects (N = 54; >70% male) were adolescent marijuana users (ages 15-18 years) with regular alcohol use (MJ + ALC; n = 24) and non-using controls (CON; n = 30) who were compared before and after 4 weeks of sequential urine toxicology to confirm abstinence. Participants underwent magnetic resonance imaging, neuropsychological assessment, and substance use assessment at both time points. Repeated-measures analysis of covariance was used to look at the main effects of group, time, and Group × Time interactions on cortical thickness and neurocognitive functioning. Bivariate correlations estimated associations between cortical thickness, substance use severity, and cognitive performance., Results: Marijuana users showed thicker cortices than controls in the left entorhinal cortex (ps < .03) before and after monitored abstinence, after adjusting for lifetime alcohol use. More lifetime marijuana use was linked to thinner cortices in temporal and frontal regions, whereas more lifetime alcohol use and heavy episodic drinking episodes was linked to thicker cortices in all four lobes (ps < .05). Age of onset of regular marijuana use was positively related to cortical thickness (ps < .03)., Conclusions: Adolescent alcohol and marijuana use may be linked to altered longer-term neurodevelopmental trajectories and compromised neural health. Cortical thickness alterations and dose-dependent associations with thickness estimates were observed both before and after monitored abstinence and suggest neural differences continue to persist 28 days after cessation of marijuana use. Neural recovery may be identified with longer follow-up periods; however, observed changes related to use severity could have implications for future psychosocial outcomes.

Background: Altered interoception, i.e., processing of stimuli from inside the body, has been considered an important component of drug-taking behavior. However, approaches to examine interoceptive sensitivity in humans have been limited. This study examined the hypothesis that adolescents with substance use disorder show altered interoceptive processing, measured by stimulating mechano-receptive C-fibers (MR-CF) via soft touch., Methods: Adolescents with substance use disorders (SUD, n=15) and comparison youth (CON, n=17) underwent functional magnetic resonance imaging (fMRI) during anticipation or reception of a positively valenced "Soft Touch" consisting of MR-CF stimulation to the palm or forearm. Visual analog scales (VAS) indexed subjective interoceptive experience (e.g., pleasantness, intensity)., Results: Across all conditions, SUD displayed attenuated left posterior insula activation compared to CON. Greater left anterior insula and right lentiform nucleus activation was evident during the application of soft touch for SUD but not for CON. Whereas for CON, greater left anterior insula activation was associated with higher pleasantness ratings, pleasantness was linked to less anterior insula activation in SUD. Finally, within SUD, attenuated posterior insula activation was related to more recent cannabis use., Conclusions: SUD adolescents exhibit blunted somatovisceral processing of pleasant stimulation, heightened sensitivity in regions responsible for processing reward value, and altered relationships between interoceptive processing and subjective experience., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Frontoparietal connections underlie key executive cognitive functions. Abnormalities in the frontoparietal network have been observed in chronic alcoholics and associated with alcohol-related cognitive deficits. It remains unclear whether neurobiological differences in frontoparietal circuitry exist in substance-naïve youth who are at-risk for alcohol use disorders. This study used functional connectivity magnetic resonance imaging and diffusion tensor imaging to examine frontoparietal connectivity and underlying white matter microstructure in 20 substance-naïve youth with a family history of alcohol dependence and 20 well-matched controls without familial substance use disorders. Youth with a family history of alcohol dependence showed significantly less functional connectivity between posterior parietal and dorsolateral prefrontal seed regions (ps<.05), as compared to family history negative controls; however, they did not show differences in white matter architecture within tracts subserving frontoparietal circuitry (ps>.34). Substance-naïve youth with a family history of alcohol dependence show less frontoparietal functional connectivity in the absence of white matter microstructural abnormalities as compared to youth with no familial risk. This may suggest a potential neurobiological marker for the development of substance use disorders., (Published by Elsevier B.V.)

Objective: Lifetime alcohol hangover and withdrawal symptoms in youth have been shown to predict poorer recall of verbal and nonverbal information, as well as reduced visuospatial skills. Some evidence has suggested that negative effects of alcohol on the brain may be buffered in part by potential neuroprotective properties of cannabinoids. We hypothesized that a history of more alcohol hangover symptoms would predict worse performances on measures of verbal and visual memory, and that this relationship would be moderated by marijuana involvement., Method: Participants were 130 adolescents (65 with histories of heavy marijuana use, and 65 non-marijuana-using controls), ranging in age from 15.7 to 19.1 years. Neuropsychological tests for visual and verbal memory and interviews assessing lifetime and recent substance use, hangover/withdrawal symptoms, and abuse and dependence criteria were administered., Results: Regression models revealed that greater alcohol hangover symptoms predicted worse verbal learning (p < .05) and memory (p < .05) (California Verbal Learning Test, Second Edition) scores for non-marijuana users, but alcohol hangover symptoms were not linked to performance among marijuana users. Alcohol hangover symptoms did not predict visual memory in either group., Conclusions: Results confirm previous studies linking adolescent heavy drinking to reduced verbal learning and memory performance. However, this relationship is not seen in adolescents with similar levels of alcohol involvement who also are heavy users of marijuana.

Background: Alcohol dependence (AD) in developmentally vulnerable adolescents is ubiquitous and confers a risk for long-term neurocognitive sequelae, yet comorbid substance use disorders and psychopathology can complicate interpretations. Here, we compare cognitive functioning in adolescents with and without AD, who are free from comorbid disorders., Methods: English- and Afrikaans-speaking adolescents (13-15 years) of mixed ancestry and low socio-economic status were recruited from the Cape Town region of South Africa. Adolescents with psychiatric, developmental, or other substance use disorders (SUDs) were excluded. AD (n=26) and control (n=26) groups were matched on age, gender, language, and level of education. Neuropsychological testing in participants' home language followed detailed medical/psychiatric evaluation., Results: Although our sample included participants who smoked tobacco, lifetime dosage of other drugs was negligible. When tobacco and other drug use as well as demographic variables were controlled, adolescents with AD performed more poorly on measures of Verbal Story Memory, Self-Monitoring, and Psychomotor Speed and Coordination., Conclusions: These preliminary results, although relatively subtle, suggest that adolescents with AD may be at increased risk for failure to reach optimal levels of neuromaturation, and may be susceptible to cognitive problems associated with protracted alcohol consumption., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Background and Objectives: The hippocampus may be vulnerable to the effects of heavy alcohol use during adolescence, which is a time of continued neurodevelopment. However, differences in hippocampal volume may be due to risk factors such as a family history (FH) of alcoholism. We examined hippocampal volumes in youth with and without a FH of alcoholism prior to the initiation of alcohol use., Methods: Participants were demographically matched adolescents (aged 12-14) with positive (n = 15; FHP) and negative (n = 15; FHN) FH of alcoholism. Each group consisted of 10 males and 5 females with minimal previous substance use. Manual hippocampal tracings were completed on high-resolution magnetic resonance images by reliable raters, and intracranial volumes were controlled in analyses., Results: FH groups did not differ on memory or hippocampal volumes, but group x gender interactions (p < .05) indicated that FHP males had larger left hippocampi than FHN males. Females showed greater left versus right hippocampal asymmetry, while males showed larger right versus left asymmetry. For all adolescents, larger right hippocampal volumes predicted poorer delayed visual memory (p < .01)., Conclusion and Significance: Alcoholism risk factors, such as family history of alcoholism, may differentially influence adolescent hippocampal development for boys as compared to girls. Results suggest that FH does not account for prior findings of reduced left hippocampal volumes in heavy drinking youth. Findings are preliminary, but suggest that future studies examining the effects of alcohol use on the adolescent brain should consider the influence of FH, especially among boys.

Background: Progressive myelination during adolescence implicates an increased vulnerability to neurotoxic substances and enduring neurocognitive consequences. This study examined the cognitive manifestations of altered white matter microstructure in chronic marijuana and alcohol-using (MJ+ALC) adolescents., Methods: Thirty-six MJ+ALC adolescents (ages 16-19) and 36 demographically similar controls were evaluated with diffusion tensor imaging (Bava et al., 2009) and neurocognitive tests. Regions of group difference in fractional anisotropy (FA) and mean diffusivity (MD) were analyzed in relation to cognitive performance., Results: In users, lower FA in temporal areas related to poorer performance on attention, working memory, and speeded processing tasks. Among regions where users had higher FA than controls, occipital FA was positively associated with working memory and complex visuomotor sequencing, whereas FA in anterior regions was negatively associated with verbal memory performance., Conclusions: Findings suggest differential influences of white matter development on cognition in MJ+ALC using adolescents than in non-using peers. Neuroadaptation may reflect additive and subtractive responses to substance use that are complicated by competing maturational processes., (Copyright 2009 Elsevier Inc. All rights reserved.)

A positive family history of alcohol use disorders (FH) is a robust predictor of personal alcohol abuse and dependence. Exposure to problem-drinking models is one mechanism through which family history influences alcohol-related cognitions and drinking patterns. Similarly, exposure to alcohol advertisements is associated with alcohol involvement and the relationship between affective response to alcohol cues and drinking behavior has not been well established. In addition, the collective contribution that FH, exposure to different types of problem-drinking models (e.g. parents, peers) and personal alcohol use have on appraisal of alcohol-related stimuli has not been evaluated with a large sample. We investigated the independent effects of FH, exposure to problem-drinking models and personal alcohol use on valence ratings of alcohol pictures in a college sample. College students (n = 227) completed measures of personal drinking and substance use, exposure to problem-drinking models, FH and ratings on affective valence of 60 alcohol pictures. Greater exposure to non-familial problem-drinkers predicted greater drinking among college students (beta = 0.17, P < 0.01). However, personal drinking was the only predictor of valence ratings of alcohol pictures (beta = -0.53, P < 0.001). Personal drinking level predicted valence ratings of alcohol cues over and above FH, exposure to problem-drinking models and demographic characteristics. This suggests that positive affective responses to alcohol pictures are more a function of personal experience (i.e. repeated heavy alcohol use) than vicarious learning.

Aim: To use the superior spatial resolution of magnetic resonance imaging (MRI) to examine differences in cerebral perfusion between young alcohol dependent and normal women., Methods: Eight alcohol dependent women and 8 controls (all ages 18-25) received single-slice resting perfusion-weighted MRI (directly proportional to brain blood flow), with slices located above the corpus callosum., Results: Alcohol-dependent women had decreased perfusion in prefrontal and left parietal regions., Conclusions: Reduced perfusion has not previously been reported in young, physically healthy alcohol dependent females, yet is consistent with previously reported decreased cerebral activity in alcohol dependence.

Background: Converging lines of evidence suggest that the hippocampus may be particularly vulnerable to deleterious effects of alcohol and marijuana use, especially during adolescence. The goal of this study was to examine hippocampal volume and asymmetry in adolescent users of alcohol and marijuana., Methods: Participants were adolescent (aged 15-18) alcohol (ALC) users (n=16), marijuana and alcohol (MJ+ALC) users (n=26), and demographically similar controls (n=21). Extensive exclusionary criteria included prenatal toxic exposure, left handedness, and psychiatric and neurologic disorders. Substance use, cognitive, and anatomical measures were collected after at least 2 days of abstinence from all substances., Results: Adolescent ALC users demonstrated a significantly different pattern of hippocampal asymmetry (p<.05) and reduced left hippocampal volume (p<.05) compared to MJ+ALC users and non-using controls. Increased alcohol abuse/dependence severity was associated with increased right>left (R>L) asymmetry and smaller left hippocampal volumes while marijuana abuse/dependence was associated with increased L>R asymmetry and larger left hippocampal volumes. Although MJ+ALC users did not differ from controls in asymmetry, functional relationships with verbal learning were found only among controls, among whom greater right than left hippocampal volume was associated with superior performance (p<.05)., Conclusions: Aberrations in hippocampal asymmetry and left hippocampal volumes were found for adolescent heavy drinkers. Further, the functional relationship between hippocampal asymmetry and verbal learning was abnormal among adolescent substance users compared to healthy controls. These findings suggest differential effects of alcohol and combined marijuana and alcohol use on hippocampal morphometry and the relationship between hippocampal asymmetry and verbal learning performance among adolescents.

Studies have suggested that teens with alcohol use disorder (AUD) can demonstrate memory deficits, but the underlying neuroanatomical substrates are unclear. The hippocampus is crucial to intact memory functioning, and it actively develops during adolescence. The current study attempted to replicate and extend previous findings suggesting that adolescents with AUD show smaller hippocampal volumes than healthy adolescents. Manual tracings of bilateral hippocampi were performed on structural magnetic resonance images of 14 adolescents (ages 15 to 17 years) with AUD and 17 healthy comparison teens. Intracranial, white, and gray matter volumes, as well as memory abilities, were also measured. Results revealed that adolescents with AUD had significantly smaller left hippocampal volumes than healthy teens, even after removal of teens with comorbid conduct disorder from the analyses. In contrast the groups did not differ in right hippocampal, intracranial, gray or white matter volumes, or memory performance. Hippocampal volumes were not related to alcohol-consumption rates. These findings indicate that adolescents with AUD, but free from other psychiatric comorbidities, have reduced left hippocampal volume. Because hippocampal volume did not relate to alcohol use characteristics, it is possible that premorbid volumetric differences could account for some of the observed group differences in hippocampal volume.

Disinhibition among alcoholics may precede or result from alcohol use disorders (AUDs). It remains unclear how disinhibition might contribute to AUD risk among youths with a family history of alcoholism (FHP). We used functional magnetic resonance imaging (fMRI) to explore inhibition-related neural risk factors for AUD. Participants were 12- to 14-year-old nondrinkers, including 12 FHP youths and 14 youths with no family history of alcoholism (FHN). Youths performed a go/no-go task during fMRI acquisition. At a conservative threshold, FHN youths showed less inhibitory response than FHP youths in the left middle frontal gyrus, despite similar task performance between groups. Using a more liberal threshold, FHP youths also demonstrated less response in additional frontal regions. These preliminary findings suggest that FHP youths show less inhibitory frontal response than FHN youths. Altered neural activation among FHP youths may underlie subsequent disinhibition and could be related to the AUD risk.

Objective: It has been suggested that neuropsychological functioning and cognitive factors influence substance use and treatment outcomes in youth. This study examined a model in which language skills moderate the extent to which expectancies about the positive effects of alcohol predict the persistence of alcohol involvement in youth over an 8-year period., Method: Participants were substance use disordered adolescents recruited from inpatient alcohol and drug treatment centers (N = 139). Exclusion criteria included major head trauma, neurological illness and psychiatric disorders. Participants were administered neuropsychological tests, expectancy questionnaires and substance involvement interviews that spanned an 8-year period from ages 16 to 24 on average. Substance involvement was assessed by self-report, collateral reports and urine toxicology screens., Results: Using latent class growth analysis of alcohol use over 8 years, participants were classified as abstainers, infrequent users, worse with time or frequent users. Language x Expectancy interactions were significant at all time points (p range .05 to .0001, effect size eta2 range 0.03 to 0.20). This interaction significantly predicted 8-year alcohol dependence symptoms over and above effects accounted for by covariates or main effects (F = 2.98, 5/100 df, p < .05; R2delta = 4%, beta = 0.21, p <.05)., Conclusions: For youths with above average language skills, positivealcohol expectancies predicted alcohol use frequency and dependence symptoms in the 8 years following treatment; expectancies were less related to outcomes for youths with poorer language scores. Results suggest that verbal skills may magnify the relationship between alcohol expectancies and drinking behavior.

Objective: Cognitive impairments influence alcohol and drug treatment outcomes, though little is known about how neurocognition affects the development of harmful substance use patterns. This study examined the influence of adolescent attention functioning on the development of substance use problems in 66 high-risk youths over an 8-year period., Method: Participants were community youths who were free from any history of substance use disorders, neurological illness, and mood, anxiety, or psychotic disorders at project intake and were administered neuropsychological tests and substance involvement interviews from ages 15 through 23 on average. Substance involvement was assessed by self-report, resource person reports, and randomly sampled toxicology screens., Results: Attention/executive functioning scores obtained at the intake neuropsychological assessment significantly predicted substance use and dependence symptoms 8 years later, even after controlling for intake substance involvement, gender, education, conduct disorder, family history of substance use disorders, and learning disabilities., Conclusions: These results suggest that adolescents with limited attentional abilities, but not necessarily attention-deficit/hyperactivity disorder diagnoses, may be at risk for developing more problematic alcohol and drug involvement. Thus prevention and treatment efforts should target youths with attentional difficulties by using programs that are effective for those with compromised concentration and processing abilities.

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.

IntroductionConsumption of fast food has been linked to psychiatric distress, violent behaviors, and impulsivity in adolescents. The relationship between eating fast food, anger, and impulsivity has not been widely investigated. The National Consortium on Alcohol and Neurodevelopment in Adolescence community-based cohort consists of 831 youth, half at elevated risk factors for substance use disorders during adolescence, followed annually.MethodsImpulsivity using Urgency, Premeditation, Perseverance, and Sensation Seeking Impulsive Behavior scale from annual assessments was examined in relation to self-reported fast-food consumption frequency and mobile application questions of anger. This study tested the hypotheses that youth anger may be predicted by fast-food consumption frequency and impulsivity using multiple regression, in addition to whether adolescent fast-food consumption frequency may be predicted by anger and impulsivity.ResultsAmong youth, higher anger levels and impulsivity predicted greater frequency of fast-food consumption, and greater fast-food consumption frequency and impulsivity predicted higher anger levels.ConclusionsThis study's longitudinal findings are consistent with those of other studies that have found fast-food consumption and anger associated with impulsivity and also reveal a bidirectional link between anger and fast-food consumption. These results may point attention to food selection considerations for those at risk of anger and poorer psychiatric outcomes.

Adolescent traumatic brain injury (TBI) has long-term effects on brain functioning and behavior, impacting neural activity under cognitive load, especially in the reward network. Adolescent TBI is also linked to risk-taking behaviors including alcohol misuse. It remains unclear how TBI and neural functioning interact to predict alcohol experimentation during adolescence. Using Adolescent Brain Cognitive Development (ABCD) study data, this project examined if TBI at ages 9-10 predicts increased odds of alcohol sipping at ages 11-13 and if this association is moderated by neural activity during the Emotional EN-Back working memory task at ages 11-13. Logistic regression analyses showed that neural activity in regions of the fronto-basal ganglia network predicted increased odds of sipping alcohol by ages 11-13 (p

ObjectiveNegative life events (NLEs), e.g., poor academic performance (controllable) or being the victim of a crime (uncontrollable), can profoundly affect the trajectory of one's life. Yet, their impact on how the brain develops is still not well understood. This investigation examined the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) dataset for the impact of NLEs on the initiation of alcohol and cannabis use, as well as underlying neural mechanisms.MethodsThis study evaluated the impact of controllable and uncontrollable NLEs on substance use initiation in 207 youth who initiated alcohol use, 168 who initiated cannabis use, and compared it to 128 youth who remained substance-naïve, using generalised linear regression models. Mediation analyses were conducted to determine neural pathways of NLE impacting substance use trajectories.ResultsDose-response relationships between controllable NLEs and substance use initiation were observed. Having one controllable NLE increased the odds of alcohol initiation by 50% (95%CI [1.18, 1.93]) and cannabis initiation by 73% (95%CI [1.36, 2.24]), respectively. Greater cortical thickness in left banks of the superior temporal sulcus mediated effects of controllable NLEs on alcohol and cannabis initiations. Greater left caudate gray-matter volumes mediated effects of controllable NLEs on cannabis initiation.ConclusionsControllable but not uncontrollable NLEs increased the odds of alcohol and cannabis initiation. Moreover, those individuals with less mature brain structures at the time of the NLEs experienced a greater impact of NLEs on subsequent initiation of alcohol or cannabis use. Targeting youth experiencing controllable NLEs may help mitigate alcohol and cannabis initiation.

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.

PurposeEvaluate changes in early adolescent substance use from May 2020 to May 2021 during the coronavirus disease 2019 pandemic using data from a prospective nationwide cohort: the Adolescent Brain Cognitive Development Study.MethodsIn 2018-2019, 9,270 youth aged 11.5-13.0 completed a prepandemic assessment of past-month alcohol and drug use, then up to seven during-pandemic assessments between May 2020 and May 2021. We compared the prevalence of substance use among same-age youth across these eight timepoints.ResultsPandemic-related decreases in the past-month prevalence of alcohol use were detectable in May 2020, grew larger over time, and remained substantial in May 2021 (0.3% vs. 3.2% prepandemic, p

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.

BackgroundThough largely substance-naïve at enrollment, a proportion of the youth in the Adolescent Brain Cognitive Development (ABCD) Study are expected to initiate substance use (SU) as they transition into later adolescence. With annual data from youth 9-13 years-old, this study aims to describe their SU patterns over time. Here, prevalence rates of use are reported, along with predicted odds of use while analyzing common risk-factors associated with youth SU.MethodsThe ABCD Study® enrolled 11,876 participants at Baseline (ages 9-10) and has followed them annually. Data through half of the third follow-up visit are available (ages 12-13; n = 6,251). SU descriptives for al psychoactive substances over time are outlined. General estimating equations (GEEs) assessed whether sociodemographic factors, internalizing and externalizing symptoms, and parental SU problems were associated with SU between Baseline and Y2 follow-up.ResultsAcross time, alcohol and nicotine remain the most used substances. Yearly rates of any SU increased (past year use: 13.9% in Y1; 14% Y2, 18.4% Y3). Cumulatively, by Y3, 39.7% of the cohort reported experimenting (e.g., sipping alcohol) with SU within their lifetime, while 7.4% reported a "full use" (a full alcohol drink, nicotine use, cannabis use, or any other SU) in their lifetime (past-year: 1.9% alcohol, 2.1% nicotine, 1.1% cannabis, 1.2% other substances). GEEs revealed ongoing longitudinal associations between sociodemographic factors, greater externalizing symptoms, and parental drug problems with increased odds of initiating SU.ConclusionsAs ABCD participants transition into their teenage years, the cohort is initiating SU at increasing (though still low) rates.

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.

BackgroundAlthough a relatively large body of research has identified multiple factors associated with adolescent substance use, less is known about earlier substance-related factors during preadolescence, including curiosity to use substances. The present study examined individual-, peer-, and parent-level domains pertaining to substance use and how these domains vary by sociodemographic subgroups and substance type.MethodsParticipants were 11,864 9- and 10-year-olds from the baseline sample of the Adolescent Brain Cognitive Development (ABCD) Study. Youth-reported measures were curiosity to use substances and perceived peer substance use. Parent-reported measures were availability of and rules about substances. Generalized logistic mixed models (GLMM) were used to compare these measures across alcohol, nicotine, and marijuana and across sociodemographic subgroupings (sex, race/ethnicity, household income, and family history of alcohol problems). GLMM was then used to examine predictors of curiosity to use by substance type.ResultsThe most striking descriptive differences were found between race/ethnicity and income categories (e.g., positive associations between greater income and greater availability of alcohol). In multivariable analyses, greater curiosity to use alcohol was associated with being male, higher household income, perceived peer alcohol use, and easy alcohol availability; greater curiosity to use nicotine was associated with being male, perceived peer cigarette use, easy availability of cigarettes, and no parental rules about cigarette use.ConclusionsThis study identified substance use-related individual-, peer-, and parent-level factors among a diverse, national sample. Findings highlight the importance of considering sociodemographic and substance-specific variability and may help identify risk and protective factors preceding adolescent substance 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.

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.

BackgroundSubstance use research has focused on family history of alcohol use disorders but less on other addictions in biological family members. We examined how parental substance use history relates to reward system functioning, specifically nucleus accumbens (NAcc) and putamen activation at age 9-10 in the Adolescent Brain Cognitive Development (ABCD) Study. This research hopes to address limitations in prior literature by focusing analyses on a large, substance-naïve sample.MethodWe included ABCD participants with valid Monetary Incentive Delay task fMRI Baseline data and parent substance use history at project baseline from Data Release 2.0 (N = 10,622). Parent-history-positive (PH+) participants had one or both biological parents with a history of two+problems with alcohol (n = 741; PH+A) and/or other drugs (n = 638; PH+D). Of participants who were parent-history-negative (PH-) for alcohol and/or drugs, a stratified random sample based on six sociodemographic variables was created and matched to the PH+group (PH-A n = 699; PH-D n = 615). The contrast of interest was anticipation of a large reward vs. neutral response.ResultsPH+A youth had more activation in the right NAcc during large reward anticipation than PH-A. PH+D youth showed enhanced left putamen activation during large reward anticipation than PH-D youth. Bayesian hypothesis testing showed moderate evidence (BF > 3) in favor of the null hypothesis.ConclusionThese findings suggest that pre-adolescents whose biological parents had a history of substance-related problems show small differences in reward processing compared to their PH- peers.

Prior research has shown that sipping of alcohol begins to emerge during childhood and is potentially etiologically significant for later substance use problems. Using a large, community sample of 9- and 10-year-olds (N = 11,872; 53% female), we examined individual differences in precocious alcohol use in the form of alcohol sipping. We focused explicitly on features that are robust and well-demonstrated correlates of, and antecedents to, alcohol excess and related problems later in the lifespan, including youth- and parent-reported externalizing traits (i.e., impulsivity, behavioral inhibition and activation) and psychopathology. Seventeen percent of the sample reported sipping alcohol outside of a religiously sanctioned activity by age 9 or 10. Several aspects of psychopathology and personality emerged as small but reliable correlates of sipping. Nonreligious sipping was related to youth-reported impulsigenic traits, aspects of behavioral activation, prodromal psychotic-like symptoms, and mood disorder diagnoses, as well as parent-reported externalizing disorder diagnoses. Religious sipping was unexpectedly associated with certain aspects of impulsivity. Together, our findings point to the potential importance of impulsivity and other transdiagnostic indicators of psychopathology (e.g., emotion dysregulation, novelty seeking) in the earliest forms of drinking behavior.

PurposeEvaluate changes in early adolescent substance use during the coronavirus disease 2019 (COVID-19) pandemic using a prospective, longitudinal, nationwide cohort.MethodsParticipants were enrolled in the Adolescent Brain Cognitive Development Study. A total of 7,842 youth (mean age = 12.4 years, range = 10.5-14.6) at 21 study sites across the U.S. completed a three-wave assessment of substance use between May and August 2020. Youth reported whether they had used alcohol, nicotine, cannabis, or other substances in the past 30 days. Data were linked to prepandemic surveys that the same youth had completed in the years 2018-2020, before the advent of the COVID-19 pandemic.ResultsPast-30-day substance use remained stable in the 6 months since stay-at-home orders were first issued in U.S. states/counties; was primarily episodic (1-2 days in the past month); and was typically limited to a single substance. Using pretest/posttest and age-period designs, we found that compared to before the pandemic, fewer youth were using alcohol and more youth were using nicotine or misusing prescription drugs. During the pandemic, youth were more likely to use substances when they were more stressed by pandemic-related uncertainty; their family experienced material hardship; their parents used alcohol or drugs; or they experienced greater depression or anxiety. Neither engagement in social distancing nor worry about COVID-19 infection was associated with substance use. Several risk factors were stronger among older (vs. younger) adolescents.ConclusionsAmong youth in early adolescence, advent of the COVID-19 pandemic was associated with decreased use of alcohol and increased use of nicotine and misuse of prescription drugs.

Many neurological diseases are characterized by gradual deterioration of brain structure andfunction. Large longitudinal MRI datasets have revealed such deterioration, in part, by applying machine and deep learning to predict diagnosis. A popular approach is to apply Convolutional Neural Networks (CNN) to extract informative features from each visit of the longitudinal MRI and then use those features to classify each visit via Recurrent Neural Networks (RNNs). Such modeling neglects the progressive nature of the disease, which may result in clinically implausible classifications across visits. To avoid this issue, we propose to combine features across visits by coupling feature extraction with a novel longitudinal pooling layer and enforce consistency of the classification across visits in line with disease progression. We evaluate the proposed method on the longitudinal structural MRIs from three neuroimaging datasets: Alzheimer's Disease Neuroimaging Initiative (ADNI, N=404), a dataset composed of 274 normal controls and 329 patients with Alcohol Use Disorder (AUD), and 255 youths from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA). In allthree experiments our method is superior to other widely used approaches for longitudinal classification thus making a unique contribution towards more accurate tracking of the impact of conditions on the brain. The code is available at https://github.com/ouyangjiahong/longitudinal-pooling.

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.

The novel coronavirus pandemic that emerged in late 2019 (COVID-19) has created challenges not previously experienced in human research. This paper discusses two large-scale NIH-funded multi-site longitudinal studies of adolescents and young adults - the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) and the Adolescent Brain Cognitive Development (ABCD) Study - and valuable approaches to learn about adaptive processes for conducting developmentally sensitive research with neuroimaging and neurocognitive testing across consortia during a global pandemic. We focus on challenges experienced during the pandemic and modifications that may guide other projects, such as implementing adapted protocols that protect the safety of participants and research staff, and addressing assessment challenges through the use of strategies such as remote and mobile assessments. Given the pandemic's disproportionate impacts on participants typically underrepresented in research, we describe efforts to retain these individuals. The pandemic provides an opportunity to develop adaptive processes that can facilitate future studies' ability to mobilize effectively and rapidly.

Academic performance significantly influences educational advancement, career opportunities, and life outcomes. The extent to which adolescent substance use and brain morphology predict academic achievement has not been extensively explored. We examined grade point average (GPA) at the time alcohol and cannabis use often starts (7th - 9th grade) and subsequently during 11th and 12th grade in a 170 physically healthy adolescents in a longitudinal study. Covariance analysis examined predictive features from 36 metrics of middle school academic performance and initiation of alcohol and cannabis use. Using a machine learning approach, GPA from 7th, 8th, and 9th grade strongly predicted 11th and 12th grade GPA, followed in predictive power by alcohol use age of onset. A machine learning approach determined 16 (from 336) baseline neuroimaging features that reflected lower thickness, area, or volume in average high school GPA drinkers compared to nondrinkers. Features that distinguished average performing drinkers from nondrinkers suggested accelerated gray matter loss during adolescence for drinkers, while high performing drinkers compared to nondrinkers may have attenuated gray matter maturation. Additional possibilities are discussed.