Associations between alcohol use and sex-specific maturation of subcortical gray matter morphometry from adolescence to adulthood: Replication across two longitudinal samples.

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.

Concordance between substance use self-report and hair analysis in community-based adolescents.

Background: Accurate drug use identification through subjective self-report and toxicological biosample (hair) analysis are necessary to determine substance use sequelae in youth. Yet consistency between self-reported substance use and robust, toxicological analysis in a large sample of youth is understudied.Objectives: We aim to assess concordance between self-reported substance use and hair toxicological analysis in community-based adolescents.Methods: Hair results by LC-MS/MS and GC-MS/MS and self-reported past-year substance use from an Adolescent Brain Cognitive Development (ABCD) Study subsample (N = 1,390; ages 9-13; 48% female) were compared. The participants were selected for hair selection through two methods: high scores on a substance risk algorithm selected 93%; 7% were low-risk, randomly selected participants. Kappa coefficients the examined concordance between self-report and hair results.Results: 10% of youth self-reported any past-year substance use (e.g. alcohol, cannabis, nicotine, and opiates), while a mostly non-overlapping 10% had hair results indicating recent substance use (cannabis, alcohol, non-prescription amphetamines, cocaine, nicotine, opiates, and fentanyl). In randomly selected low-risk cases, 7% were confirmed positive in hair. Combining methods, 19% of the sample self-reported substance use and/or had a positive hair sample. Kappa coefficient of concordance between self-report and hair results was low (kappa = 0.07; p = .007).Conclusions: Hair toxicology identified substance use in high-risk and low-risk ABCD cohort subsamples. Given low concordance between hair results and self-report, reliance on either method alone would incorrectly categorize 9% as non-users. Multiple methods for characterizing substance use history in youth improves accuracy. Larger representative samples are needed to assess the prevalence of substance use in youth.

Prenatal tobacco exposure associations with physical health and neurodevelopment in the ABCD cohort.

OBJECTIVE: To investigate the strength and reproducibility of the teratogenic impact of prenatal tobacco exposure (PTE) on child physical health and neurodevelopmental outcomes, in the context of intersecting sociodemographic and other prenatal correlates, and test if early postnatal health mediates PTE associations with childhood outcomes. METHOD: Among 9-10-year-olds (N = 8,803) in the Adolescent Brain Cognitive Development Study, linear mixed-effect models tested PTE associations with birth and childhood outcomes of physical health, cognitive performance, and brain structure, controlling for confounding sociodemographic and prenatal health correlates. Mediation analysis tested the extent to which health at birth explained the associations between PTE and childhood outcomes. RESULTS: PTE was reported by 12% of mothers (8% [n = 738] pre-knowledge of pregnancy only, and 4% [n = 361] pre- and post-knowledge of pregnancy). PTE was highest for children with a risk for passive smoke exposure. Overall, children with any PTE had shorter breastfeeding durations than those without PTE, and PTE following knowledge of pregnancy was associated with being small for gestational age having lower birth weight, and obesity and lower cortical volume and surface area in childhood. Among children from high-parent education households, any PTE was related to lower cognitive performance, which was partially mediated by duration of breastfeeding. CONCLUSIONS: PTE was linked to poorer health indicators at birth and neurodevelopmental outcomes at age 9-10 years in a large community cohort, independent of sociodemographic factors. Efficacious interventions for smoking-cessation during pregnancy are still needed and should incorporate support for breastfeeding to promote healthier development. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Individual-, peer-, and parent-level substance use-related factors among 9- and 10-year-olds from the ABCD Study: Prevalence rates and sociodemographic differences.

Background: Although 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. Methods: Participants 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. Results: The 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. Conclusions: This 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.

Did the acute impact of the COVID-19 pandemic on drinking or nicotine use persist? Evidence from a cohort of emerging adults followed for up to nine years.

OBJECTIVE: This 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. METHOD: Data 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. RESULTS: Compared 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. CONCLUSION: Initial effects of the pandemic on alcohol use faded by June 2021, and on average there was little effect of the pandemic on nicotine use.

Cognitive Functioning Related to Binge Alcohol and Cannabis Co-Use in Abstinent Adolescents and Young Adults.

OBJECTIVE: Despite preliminary evidence of unique acute cognitive and psychopharmacological changes attributable to combined alcohol and cannabis use, few studies have investigated more chronic effects of same-day co-use, particularly during neurodevelopmentally sensitive periods. Therefore, relationships between past-month binge alcohol and cannabis co-use and cognitive functioning were examined in adolescents and young adults. METHOD: Data from the Imaging Data in Emerging Adults with Addiction (IDEAA) Consortium were used to assess cognitive functioning in emerging adults with a large range of substance use (n = 232; 15-26 years old) who were abstinent for at least 3 weeks. Multiple regressions assessed cognitive functioning by past-month binge episodes, cannabis use episodes, and same-day co-use, controlling for covariates (e.g., study site, sex, age). RESULTS: After correcting for multiple comparisons, more past-month co-use episodes were related to decreased Ruff 2&7 selective attention accuracy (p = .036). Sex significantly covaried with California Verbal Learning Test-Second Edition initial learning. CONCLUSIONS: Although few significant relationships were found and effect sizes are modest, the persistence of an effect on attention despite a period of sustained abstinence highlights the need to carefully investigate patterns of substance use and potential independent and interactive effects on the developing brain.

Is (poly-) substance use associated with impaired inhibitory control? A mega-analysis controlling for confounders.

Many studies have reported that heavy substance use is associated with impaired response inhibition. Studies typically focused on associations with a single substance, while polysubstance use is common. Further, most studies compared heavy users with light/non-users, though substance use occurs along a continuum. The current mega-analysis accounted for these issues by aggregating individual data from 43 studies (3610 adult participants) that used the Go/No-Go (GNG) or Stop-signal task (SST) to assess inhibition among mostly "recreational" substance users (i.e., the rate of substance use disorders was low). Main and interaction effects of substance use, demographics, and task-characteristics were entered in a linear mixed model. Contrary to many studies and reviews in the field, we found that only lifetime cannabis use was associated with impaired response inhibition in the SST. An interaction effect was also observed: the relationship between tobacco use and response inhibition (in the SST) differed between cannabis users and non-users, with a negative association between tobacco use and inhibition in the cannabis non-users. In addition, participants' age, education level, and some task characteristics influenced inhibition outcomes. Overall, we found limited support for impaired inhibition among substance users when controlling for demographics and task-characteristics.

Preliminary evidence that computerized approach avoidance training is not associated with changes in fMRI cannabis cue reactivity in non-treatment-seeking adolescent cannabis users.

BACKGROUND: Cognitive Bias Modification (CBM) has garnered interest as a potential addiction treatment. CBM interventions such as Approach Avoidance Training (AAT) are designed to alter automatic tendencies to approach drugs or drug-related cues. In our previous work, the cannabis AAT (CAAT) reduced cannabis approach bias, which was related to reduced cannabis use, among 80 non-treatment-seeking cannabis-using youth (Jacobus et al., 2018). In this preliminary examination, a subsample of these youth underwent neuroimaging to explore CAAT's effect on cannabis cue-related neural activation. METHODS: Sub-study participants were 41 cannabis-using youth ages 17-21 (mean age = 18.83; 47.5% female). Participants completed a cannabis cue-reactivity task during a functional MRI scan pre- and post CAAT-training or CAAT-sham to examine CAAT-related neural changes. RESULTS: Thirty-seven youth completed all six CAAT (n = 19) or CAAT-sham (n = 18) training sessions and had usable neuroimaging data. The group*time interaction on cannabis approach bias reached trend-level significance (p = .055). Change in approach bias slopes from pre-to post-treatment was positive for CAAT-sham (increased approach bias) and negative for CAAT-training (change to avoidance bias), consistent with the larger study. No significant changes emerged for cannabis cue-induced activation following CAAT-training or CAAT-sham in whole brain or region of interest analyses. However, active CAAT-training was associated with small-to-medium decreases in amygdala (Cohen's dz = 0.36) and medial prefrontal cortex (Cohen's dz = 0.48) activation to cannabis cues. CONCLUSIONS: Despite reducing cannabis use in the larger sample, CAAT-training did not alter neural cannabis cue-reactivity in the sub-study compared to CAAT-sham. More research is needed to understand neural mechanisms underlying AAT-related changes in substance use.

Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects.

OBJECTIVE: Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes. METHOD: Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings. RESULTS: Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent control subjects. CONCLUSIONS: The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine.

Investigating a novel fMRI cannabis cue reactivity task in youth.

OBJECTIVE: Adult and adolescent studies suggest increased motivational responses to cannabis cues among regular cannabis users. However, functional magnetic resonance imaging (fMRI) studies have not explored neural activation in response to visual cannabis cues among adolescents in the United States. Gaining a better understanding of the neural circuits related to cue-elicited craving during adolescence may shed light on the neural basis for the development of problematic cannabis use that could ultimately be targeted for interventions. METHODS: 41 non-treatment-seeking youth (ages 17-21; mean age = 18.83; 46.3% female) who reported regular cannabis use underwent fMRI scanning involving a visual cannabis cue task and completed self-report and biological measures. Whole-brain activation was examined for cannabis cues compared to non-cannabis cues, and for active versus passive cannabis cues. Associations between self-reported substance use and task activation were examined. RESULTS: Cannabis images were identifiable to adolescents and were rated as more rewarding than matched non-cannabis images (p < .05). Greater activation was found for the cannabis cues compared to non-cannabis cues in bilateral posterior cingulate, cuneus, fusiform, precuneus, inferior temporal and parahippocampal gyri, as well as left thalamus, medial frontal and superior frontal gyri. Cue-elicited activation was not significantly associated with self-reported cannabis use (ps > 0.05). No differences were observed for the active versus passive cue contrast. CONCLUSIONS: Cannabis-using youth show more activation to cannabis cues than non-cannabis cues in brain regions underlying incentive salience, reward, and visual attention. This task could be useful for future studies examining neural underpinnings of reward processes in adolescent cannabis users.

Blunted Frontostriatal Blood Oxygen Level-Dependent Signals Predict Stimulant and Marijuana Use.

BACKGROUND: Occasional recreational stimulant (amphetamine and cocaine) use is an important public health problem among young adults because 16% of those who experiment develop stimulant use disorder. This study aimed to determine whether behavioral and/or neural processing measures can forecast the transition from occasional to problematic stimulant use. METHODS: Occasional stimulant users completed a Risky Gains Task during functional magnetic resonance imaging and were followed up 3 years later. Categorical analyses tested whether blood oxygen level-dependent (BOLD) responses differentiated occasional stimulant users who became problem stimulant users (n = 35) from those who desisted from stimulant use (n = 75) at follow-up. Dimensional analyses (regardless of problem stimulant user or desisted stimulant use status; n = 144) tested whether BOLD responses predicted baseline and follow-up stimulant and marijuana use. RESULTS: Categorical results indicated that relative to those who desisted from stimulant use, problem stimulant users 1) made riskier decisions after winning feedback; 2) exhibited lower frontal, insular, and striatal BOLD responses to win/loss feedback after making risky decisions; and 3) displayed lower thalamic but greater temporo-occipital BOLD responses to risky losses than to risky wins. In comparison, dimensional results indicated that lower BOLD signals to risky choices than to safe choices in frontal, striatal, and additional regions predicted greater marijuana use at follow-up. CONCLUSIONS: Taken together, blunted frontostriatal signals during risky choices may quantify vulnerability to future marijuana consumption, whereas blunted frontostriatal signals to risky outcomes mark risk for future stimulant use disorder. These behavioral and neural processing measures may prove to be useful for identifying ultra-high risk individuals prior to onset of problem drug use.

Effects of sleep on substance use in adolescents: a longitudinal perspective.

Substance use (SU) and sleep problems appear interrelated, but few studies have examined the influence of adolescent sleep patterns on development of SU disorders. This study prospectively examined the influence of sleep habits on subsequent SU in youth who later transitioned into heavy drinking. At time 1 (T1), participants (n = 95) were substance-naive 12- to 14-year-olds. Path-analytic models examined whether the effects of T1 risk factors (familial SU disorder, inhibition control, and externalizing and internalizing traits) on time 3 (M = 19.8 years old) tobacco, alcohol, and cannabis were mediated by time 2 (M = 15.1 years old) sleep chronotype, daytime sleepiness, and erratic sleep/wake behaviors. Significant direct path effects of T1 risk factors and time 2 sleep behaviors on time 3 SU were found, Ps < 0.05. In models that examined the effect of each individual sleep behavior separately on SU, more erratic sleep/wake and greater daytime sleepiness predicted higher lifetime use events for all substances (Ps < 0.01). Higher evening chronotype tendencies predicted lower tobacco and higher alcohol and cannabis lifetime use events (Ps < 0.01). Erratic sleep/wake behaviors mediated the effect of inhibitory control on subsequent SU; less erratic sleep/wake behaviors predicted better inhibition control ( ß̂= -0.20, P < 0.05). Early-mid adolescent psychiatric health and sleep behaviors prior to drinking onset predicted greater SU 5 years later. Participants were substance-naïve at baseline, allowing for the examination of temporal order in the relationship between sleep problems and alcohol use. Early adolescent sleep problems may be an important risk factor for SU in later life.

Structural brain anomalies in healthy adolescents in the NCANDA cohort: relation to neuropsychological test performance, sex, and ethnicity.

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.

Adolescent cortical thickness pre- and post marijuana and alcohol initiation.

Cortical thickness abnormalities have been identified in youth using both alcohol and marijuana. However, limited studies have followed individuals pre- and post initiation of alcohol and marijuana use to help identify to what extent discrepancies in structural brain integrity are pre-existing or substance-related. Adolescents (N=69) were followed from ages 13 (pre-initiation of substance use, baseline) to ages 19 (post-initiation, follow-up). Three subgroups were identified, participants that initiated alcohol use (ALC, n=23, >20 alcohol use episodes), those that initiated both alcohol and marijuana use (ALC+MJ, n=23, >50 marijuana use episodes) and individuals that did not initiate either substance regularly by follow-up (CON, n=23, <3 alcohol use episodes, no marijuana use episodes). All adolescents underwent neurocognitive testing, neuroimaging, and substance use and mental health interviews. Significant group by time interactions and main effects on cortical thickness estimates were identified for 18 cortical regions spanning the left and right hemisphere (ps<0.05). The vast majority of findings suggest a more substantial decrease, or within-subjects effect, in cortical thickness by follow-up for individuals who have not initiated regular substance use or alcohol use only by age 19; modest between-group differences were identified at baseline in several cortical regions (ALC and CON>ALC+MJ). Minimal neurocognitive differences were observed in this sample. Findings suggest pre-existing neural differences prior to marijuana use may contribute to initiation of use and observed neural outcomes. Marijuana use may also interfere with thinning trajectories that contribute to morphological differences in young adulthood that are often observed in cross-sectional studies of heavy marijuana users.

Learning and Memory in Adolescent Moderate, Binge, and Extreme-Binge Drinkers.

BACKGROUND: Binge drinking has been linked to neurocognitive disadvantages in youth, but it is unclear whether drinking at particularly heavy levels uniquely affects neurocognitive performance. This study prospectively examined (1) whether initiating moderate, binge, or extreme-binge drinking in adolescence differentially influences subsequent learning and memory performances, and (2) whether dosage of alcohol consumption is linearly associated with changes in learning and memory over 6 years of adolescence. METHODS: Participants, who later transitioned into drinking, were administered verbal learning and memory (VLM) assessments at project intake prior to the onset of substance use (age 12 to 16 years), and at follow-up approximately 6 years later (N = 112). Participants were grouped based on alcohol involvement at follow-up as follows: moderate (≤4 drinks per occasion), binge (5+ drinks per occasion), or extreme-binge (10+ drinks per occasion) drinkers. RESULTS: Despite equivalent performances prior to onset of drinking, extreme-binge drinkers performed worse than moderate drinkers on verbal learning, and cued and free short delayed recall (ps < 0.05); binge drinkers did not differ from the other groups. No distinct thresholds in alcohol quantity to differentiate the 3 groups were detected, but estimated peak blood alcohol concentrations were linearly associated with verbal learning (ß^ = -0.24), and immediate (ß^ = -0.27), short delay free (ß^ = -0.28) and cued (ß^ = -0.30), and long delay free (ß^ = -0.24) and cued (ß^ = -0.27) recall (ps < 0.05). CONCLUSIONS: Drinking quantity during adolescence appears to adversely affect VLM in a dose-dependent manner. The acquisition of new verbal information may be particularly affected, notably for those who initiated drinking 10+ drinks in an occasion. Although classification of drinkers into categories remains critical in the study of alcohol, it is important to consider that subtle differences may exist within drinking categories.

The National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA): A Multisite Study of Adolescent Development and Substance Use.

OBJECTIVE: During 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. METHOD: A 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. RESULTS: The 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. CONCLUSIONS: NCANDA 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.

Bayesian neural adjustment of inhibitory control predicts emergence of problem stimulant use.

Bayesian ideal observer models quantify individuals' context- and experience-dependent beliefs and expectations about their environment, which provides a powerful approach (i) to link basic behavioural mechanisms to neural processing; and (ii) to generate clinical predictors for patient populations. Here, we focus on (ii) and determine whether individual differences in the neural representation of the need to stop in an inhibitory task can predict the development of problem use (i.e. abuse or dependence) in individuals experimenting with stimulants. One hundred and fifty-seven non-dependent occasional stimulant users, aged 18-24, completed a stop-signal task while undergoing functional magnetic resonance imaging. These individuals were prospectively followed for 3 years and evaluated for stimulant use and abuse/dependence symptoms. At follow-up, 38 occasional stimulant users met criteria for a stimulant use disorder (problem stimulant users), while 50 had discontinued use (desisted stimulant users). We found that those individuals who showed greater neural responses associated with Bayesian prediction errors, i.e. the difference between actual and expected need to stop on a given trial, in right medial prefrontal cortex/anterior cingulate cortex, caudate, anterior insula, and thalamus were more likely to exhibit problem use 3 years later. Importantly, these computationally based neural predictors outperformed clinical measures and non-model based neural variables in predicting clinical status. In conclusion, young adults who show exaggerated brain processing underlying whether to 'stop' or to 'go' are more likely to develop stimulant abuse. Thus, Bayesian cognitive models provide both a computational explanation and potential predictive biomarkers of belief processing deficits in individuals at risk for stimulant addiction.

Effects of Emerging Alcohol and Marijuana Use Behaviors on Adolescents' Neuropsychological Functioning Over Four Years.

OBJECTIVE: Adolescence is a period of neuromaturation concomitant with increased substance involvement. Most substance use studies of adolescents have focused on categorical classifications (e.g., dependent vs. nondependent), but little is known about the influence of specific substance use behaviors on cognitive functioning in youth. METHOD: This study prospectively evaluated the quantitative effects of different substance use behaviors on neuropsychological functioning. A cognitive test battery was administered at baseline (ages 12-14 years), before substance use initiation, and at follow-up (M = 4.0 years, SD = 2.0) to evaluate changes in verbal memory, visuospatial ability, psychomotor speed, processing speed, and working memory. Robust regressions examined substance use behaviors as predictors of neuropsychological functioning (N = 234). RESULTS: Several substance use behaviors predicted follow-up neuropsychological functioning above and beyond effects of baseline performance on the same measure (ps < .05). Specifically, more alcohol use days predicted worse verbal memory (ß = -.15) and visuospatial ability (ß = -.19). More postdrinking effects (ß = -.15) and greater drug use (ß = -.11) predicted worse psychomotor speed. Processing speed was not predicted by substance involvement (ps > .05). Unexpectedly, more alcohol use predicted better working memory performance (ß = .12). CONCLUSIONS: The frequency and intensity of adolescent alcohol use may be more intricately linked to neuropsychological outcomes than previously considered. The low prevalence of substance use disorder in the sample suggests that subdiagnostic users may still experience adverse effects to verbal memory, visuospatial functioning, and psychomotor speed after initiating intense or frequent alcohol use.

Under pressure: adolescent substance users show exaggerated neural processing of aversive interoceptive stimuli.

AIMS: Adolescents with substance use disorders (SUD) exhibit hyposensitivity to pleasant internally generated (interoceptive) stimuli and hypersensitivity to external rewarding stimuli. It is unclear whether similar patterns exist for aversive interoceptive stimuli. We compared activation in the insular cortex and other brain regions during the anticipation and experience of aversive stimuli between adolescents with SUD and those without. DESIGN: Cross-sectional experimental study with two groups. PARTICIPANTS: Adolescents (ages 15-17 years) with an alcohol or marijuana SUD (n=18) and healthy comparison subjects (CON, n=15). Participants were recruited by distributing flyers at local high schools. SETTING: Keck Imaging Center, University of California San Diego, CA, USA. MEASUREMENTS: Behavioral and neural responses to a continuous performance task with inspiratory breathing load recorded during an fMRI session. Questionnaires assessed life-time drug use, anxiety, sensation-seeking, impulsivity, affect and bodily awareness. Visual analog scales assessed drug craving and breathing load responses. FINDINGS: Across subjects, experience of breathing load elicited greater bilateral anterior and posterior insula (AI and PI, respectively) activation than anticipation (F(1,31)=4.16, P<0.05). SUD exhibited greater left AI and bilateral PI activation during breathing load than anticipation, compared with CON (F(1,31)=4.16, P<0.05). In contrast, CON showed greater activation during anticipation than breathing load in left PI, compared with SUD (F(1,31)=4.16, P<0.05). CONCLUSIONS: Adolescents with alcohol and marijuana substance use disorders may be hypersensitive to aversive interoceptive stimuli.

Neuropsychological performance in adolescent marijuana users with co-occurring alcohol use: A three-year longitudinal study.

OBJECTIVE: The effect of adolescent marijuana use on brain development remains unclear despite relaxing legal restrictions, decreased perceived harm, and increasing use rates among youth. The aim of this 3-year prospective study was to evaluate the long-term neurocognitive effects of adolescent marijuana use. METHOD: Adolescent marijuana users with concomitant alcohol use (MJ + ALC, n = 49) and control teens with limited substance use histories (CON, n = 59) were given neuropsychological and substance use assessments at project baseline, when they were ages 16-19. They were then reassessed 18 and 36 months later. Changes in neuropsychological measures were evaluated with repeated measures analysis of covariance (ANCOVA), controlling for lifetime alcohol use, and examined the effects of group, time, and group by time interactions on cognitive functioning. RESULTS: MJ + ALC users performed significantly worse than controls, across time points, in the domains of complex attention, memory, processing speed, and visuospatial functioning (ps <.05). Earlier age of marijuana use onset was associated with poorer processing speed and executive functioning by the 3-year follow-up (ps ≤.02). CONCLUSIONS: Frequent marijuana use throughout adolescence and into young adulthood appeared linked to worsened cognitive performance. Earlier age of onset appears to be associated with poorer neurocognitive outcomes that emerge by young adulthood, providing further support for the notion that the brain may be uniquely sensitive to frequent marijuana exposure during the adolescent phase of neurodevelopment. Continued follow-up of adolescent marijuana users will determine the extent of neural recovery that may occur if use abates.