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Early adolescent drinking onset is linked to myriad negative consequences. Using the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) baseline to year 8 data, this study (1) leveraged best subsets selection and Cox Proportional Hazards regressions to identify the most robust predictors of adolescent first and regular drinking onset, and (2) examined the clinical utility of drinking onset in forecasting later binge drinking and withdrawal effects. Baseline predictors included youth psychodevelopmental characteristics, cognition, brain structure, family, peer, and neighborhood domains. Participants (N=538) were alcohol-naïve at baseline. The strongest predictors of first and regular drinking onset were positive alcohol expectancies (Hazard Ratios [HRs]=1.67-1.87), easy home alcohol access (HRs=1.62-1.67), more parental solicitation (e.g., inquiring about activities; HRs=1.72-1.76), and less parental control and knowledge (HRs=.72-.73). Robust linear regressions showed earlier first and regular drinking onset predicted earlier transition into binge and regular binge drinking (βs=0.57-0.95). Zero-inflated Poisson regressions revealed that delayed first and regular drinking increased the likelihood (Incidence Rate Ratios [IRR]=1.62 and IRR=1.29, respectively) of never experiencing withdrawal. Findings identified behavioral and environmental factors predicting temporal paths to youthful drinking, dissociated first from regular drinking initiation, and revealed adverse sequelae of younger drinking initiation, supporting efforts to delay drinking onset., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Unrelated to the work reported in this paper, Massimiliano de Zambotti reports a relationship with Noctrix Health Inc. that includes: funding grants. Massimiliano de Zambotti reports a relationship with Verily Life Sciences LLC that includes: funding grants. Massimiliano de Zambotti reports a relationship with Honda Motor Co Ltd that includes: funding grants. Massimiliano de Zambotti reports a relationship with Lisa Health, Inc that includes: employment and equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest None of the authors have biomedical financial interests or conflicts of interest with the reported data or their interpretation., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 < .05). TBI and left frontal pole activity interacted to predict alcohol sipping (OR = 0.507, 95% CI [0.303 - 0.846], p = .009) - increased activity predicted decreased odds of alcohol sipping for those with a TBI (OR = 0.516, 95% CI [0.314 - 0.850], p = .009), but not for those without (OR = 0.971, 95% CI [0.931 -1.012], p = .159). These findings suggest that for youth with a TBI, increased BOLD activity in the frontal pole, underlying working memory, may be uniquely protective against the early initiation of alcohol experimentation. Future work will examine TBI and alcohol misuse in the ABCD cohort across more time points and the impact of personality traits such as impulsivity on these associations., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest. Dr. Max provides expert testimony in cases of traumatic brain injury on an ad hoc basis for plaintiffs and defendants on a more or less equal ratio. This activity constitutes approximately 5% of his professional activities., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Evaluate 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., Methods: In 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., Results: Pandemic-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 <.001). Pandemic-related increases in inhalant use (p = .04) and prescription drug misuse (p < .001) were detectable in May 2020, shrunk over time, and were smaller but still detectable in May 2021(0.1%-0.2% vs. 0% pre-pandemic). Pandemic-related increases in nicotine use were detectable between May 2020 and March 2021 and no longer significantly different from prepandemic levels in May 2021 (0.5% vs. 0.2% prepandemic, p = .09). There was significant heterogeneity in pandemic-related change in substance use at some timepoints, with increased rates among youth identified as Black or Hispanic or in lower-income families versus stable or decreased rates among youth identified as White or in higher-income families., Discussion: Among youth ages 11.5-13.0 years old, rates of alcohol use remained dramatically reduced in May 2021 relative to prepandemic and rates of prescription drug misuse and inhalant use remained modestly increased. Differences remained despite the partial restoration of prepandemic life, raising questions about whether youth who spent early adolescence under pandemic conditions may exhibit persistently different patterns of substance use., (Copyright © 2023 Society for Adolescent Health and Medicine. All rights reserved.)

Our study characterized associations between three indicators of COVID-19's community-level impact in 20 geographically diverse metropolitan regions and how worried youth and their caregivers in the Adolescent Brain Cognitive Development℠ Study have been about COVID-19. County-level COVID-19 case/death rates and monthly unemployment rates were geocoded to participants' addresses. Caregivers' (vs. youths') COVID-19-related worry was more strongly associated with COVID-19's community impact, independent of sociodemographics and pre-pandemic anxiety levels, with these associations varying by location. Public-health agencies and healthcare providers should avoid adopting uniform "one-size-fits-all" approaches to addressing COVID-19-related emotional distress and must consider specific communities' needs, challenges, and strengths., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Temporal stability of individual differences is an important prerequisite for accurate tracking of prospective relationships between neurocognition and real-world behavioral outcomes such as substance abuse and psychopathology. Here we report age-related changes and longitudinal test-retest stability (TRS) for the Neurocognition battery of the Adolescent Brain and Cognitive Development (ABCD) study, which included the NIH Toolbox (TB) Cognitive Domain and additional memory and visuospatial processing tests administered at baseline (ages 9-11) and two-year follow-up. As expected, performance improved significantly with age, but the effect size varied broadly, with Pattern Comparison and the Crystallized Cognition Composite showing the largest age-related gain (Cohen's d:.99 and.97, respectively). TRS ranged from fair (Flanker test: r = 0.44) to excellent (Crystallized Cognition Composite: r = 0.82). A comparison of longitudinal changes and cross-sectional age-related differences within baseline and follow-up assessments suggested that, for some measures, longitudinal changes may be confounded by practice effects and differences in task stimuli or procedure between baseline and follow-up. In conclusion, a subset of measures showed good stability of individual differences despite significant age-related changes, warranting their use as prospective predictors. However, caution is needed in the interpretation of observed longitudinal changes as indicators of neurocognitive development., (Copyright © 2022. Published by Elsevier Ltd.)

The Adolescent Brain Cognitive Development (ABCD) SM study aims to retain a demographically diverse sample of youth and one parent across 21 sites throughout its 10-year protocol while minimizing selective (systematic) attrition. To evaluate the effectiveness of these efforts, the ABCD Retention Workgroup (RW) has employed a data-driven approach to examine, track, and intervene via three key metrics: (1) which youth completed visits late; (2) which youth missed visits; and (3) which youth withdrew from the study. The RW actively examines demographic (race, education level, family income) and site factors (visit satisfaction, distance from site, and enrollment in ancillary studies) to strategize efforts that will minimize disengagement and loss of participating youth and parents. Data showed that the most robust primary correlates of late visits were distance from study site, race, and parental education level. Race, lower parental education level, parental employment status, and lower family income were associated with higher odds of missed visits, while being enrolled in one of the ancillary studies was associated with lower odds of missed visits. Additionally, parents who were primary Spanish speakers withdrew at slightly higher rates. These findings provide insight into future targets for proactive retention efforts by the ABCD RW., (Copyright © 2022. Published by Elsevier Ltd.)

Purpose: Adolescence is characterized by dramatic physical, social, and emotional changes, making teens particularly vulnerable to the mental health effects of the COVID-19 pandemic. This longitudinal study identifies young adolescents who are most vulnerable to the psychological toll of the pandemic and provides insights to inform strategies to help adolescents cope better in times of crisis., Methods: A data-driven approach was applied to a longitudinal, demographically diverse cohort of more than 3,000 young adolescents (11-14 years) participating in the ongoing Adolescent Brain Cognitive Development Study in the United States, including multiple prepandemic visits and three assessments during the COVID-19 pandemic (May-August 2020). We fitted machine learning models and provided a comprehensive list of predictors of psychological distress in individuals., Results: Positive affect, stress, anxiety, and depressive symptoms were accurately detected with our classifiers. Female sex and prepandemic internalizing symptoms and sleep problems were strong predictors of psychological distress. Parent- and youth-reported pandemic-related psychosocial factors, including poorer quality and functioning of family relationships, more screen time, and witnessing discrimination in relation to the pandemic further predicted youth distress. However, better social support, regular physical activities, coping strategies, and healthy behaviors predicted better emotional well-being., Discussion: Findings highlight the importance of social connectedness and healthy behaviors, such as sleep and physical activity, as buffering factors against the deleterious effects of the pandemic on adolescents' mental health. They also point to the need for greater attention toward coping strategies that help the most vulnerable adolescents, particularly girls and those with prepandemic psychological problems., (Copyright © 2021. Published by Elsevier Inc.)

The Adolescent Brain Cognitive Development SM (ABCD) study is a longitudinal study of adolescent brain development and health that includes over 11,800 youth in the United States. The ABCD study includes broad developmental domains, and gender and sexuality are two of these with noted changes across late childhood and early adolescence. The Gender Identity and Sexual Health (GISH) workgroup recommends measures of gender and sexuality for the ABCD study, prioritizing those that are developmentally sensitive, capture individual differences in the experience of gender and sexuality, and minimize participant burden. This manuscript describes the gender and sexuality measures used in ABCD and provides guidance for researchers using these data. Data showing the utility of these measures and longitudinal trends are presented. Including assessment of gender and sexuality in ABCD allows for characterization of developmental trajectories of gender and sexuality, and the broad scope of ABCD data collection allows examination of identity development in an intersectional manner., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Advances in our understanding of risk and resilience factors in adolescent brain health and development increasingly demand a broad set of assessment tools that consider a youth's peer, family, school, neighborhood, and cultural contexts in addition to neurobiological, genetic, and biomedical information. The Culture and Environment (CE) Workgroup (WG) of the Adolescent Brain Cognitive Development (ABCD) Study curates these important components of the protocol throughout ten years of planned data collection. In this report, the CE WG presents an update on the evolution of the ABCD Study® CE protocol since study inception (Zucker et al., 2018), as well as emerging findings that include CE measures. Background and measurement characteristics of instruments present in the study since baseline have already been described in our 2018 report, and therefore are only briefly described here. New measures introduced since baseline are described in more detail. Descriptive statistics on all measures are presented based on a total sample of 11,000+ youth and their caregivers assessed at baseline and the following two years. Psychometric properties of the measures, including longitudinal aspects of the data, are reported, along with considerations for future measurement waves. The CE WG ABCD® components are an essential part of the overall protocol that permits characterization of the unique cultural and social environment within which each developing brain is transactionally embedded., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The Adolescent Brain Cognitive Development (ABCD) Study of 11,880 youth incorporates a comprehensive range of measures assessing predictors and outcomes related to mental health across childhood and adolescence in participating youth, as well as information about family mental health history. We have previously described the logic and content of the mental health assessment battery at Baseline and 1-year follow-up. Here, we describe changes to that battery and issues and clarifications that have emerged, as well as additions to the mental health battery at the 2-, 3-, 4-, and 5-year follow-ups. We capitalize on the recent release of longitudinal data for caregiver and youth report of mental health data to evaluate trajectories of dimensions of psychopathology as a function of demographic factors. For both caregiver and self-reported mental health symptoms, males showed age-related decreases in internalizing and externalizing symptoms, while females showed an increase in internalizing symptoms with age. Multiple indicators of socioeconomic status (caregiver education, family income, financial adversity, neighborhood poverty) accounted for unique variance in both caregiver and youth-reported externalizing and internalizing symptoms. These data highlight the importance of examining developmental trajectories of mental health as a function of key factors such as sex and socioeconomic environment., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Our brain is constantly shaped by our immediate environments, and while some effects are transient, some have long-term consequences. Therefore, it is critical to identify which environmental risks have evident and long-term impact on brain development. To expand our understanding of the environmental context of each child, the Adolescent Brain Cognitive Development (ABCD) Study® incorporates the use of geospatial location data to capture a range of individual, neighborhood, and state level data based on the child's residential location in order to elucidate the physical environmental contexts in which today's youth are growing up. We review the major considerations and types of geocoded information incorporated by the Linked External Data Environmental (LED) workgroup to expand on the built and natural environmental constructs in the existing and future ABCD Study data releases. Understanding the environmental context of each youth furthers the consortium's mission to understand factors that may influence individual differences in brain development, providing the opportunity to inform public policy and health organization guidelines for child and adolescent health., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The Adolescent Brain Cognitive Development ™ Study (ABCD Study®) is an open-science, multi-site, prospective, longitudinal study following over 11,800 9- and 10-year-old youth into early adulthood. The ABCD Study aims to prospectively examine the impact of substance use (SU) on neurocognitive and health outcomes. Although SU initiation typically occurs during teen years, relatively little is known about patterns of SU in children younger than 12., Methods: This study aims to report the detailed ABCD Study® SU patterns at baseline (n = 11,875) in order to inform the greater scientific community about cohort's early SU. Along with a detailed description of SU, we ran mixed effects regression models to examine the association between early caffeine and alcohol sipping with demographic factors, externalizing symptoms and parental history of alcohol and substance use disorders (AUD/SUD)., Primary Results: At baseline, the majority of youth had used caffeine (67.6 %) and 22.5 % reported sipping alcohol (22.5 %). There was little to no reported use of other drug categories (0.2 % full alcohol drink, 0.7 % used nicotine, <0.1 % used any other drug of abuse). Analyses revealed that total caffeine use and early alcohol sipping were associated with demographic variables (p's<.05), externalizing symptoms (caffeine p = 0002; sipping p = .0003), and parental history of AUD (sipping p = .03)., Conclusions: ABCD Study participants aged 9-10 years old reported caffeine use and alcohol sipping experimentation, but very rare other SU. Variables linked with early childhood alcohol sipping and caffeine use should be examined as contributing factors in future longitudinal analyses examining escalating trajectories of SU in the ABCD Study cohort., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Evaluate changes in early adolescent substance use during the coronavirus disease 2019 (COVID-19) pandemic using a prospective, longitudinal, nationwide cohort., Methods: Participants 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., Results: Past-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., Conclusions: Among 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., (Copyright © 2021 Society for Adolescent Health and Medicine. All rights reserved.)

Childhood adversity has been associated with elevated risk for psychopathology. We investigated whether development of functional brain networks important for executive function (EF) could serve as potential mediators of this association. We analyzed data of 475 adolescents, a subsample of the multisite longitudinal NCANDA (National Consortium on Alcohol and Neurodevelopment in Adolescence) cohort with completed measures of childhood trauma, resting-state functional brain connectivity data, and symptoms of internalizing and externalizing psychopathology at baseline and follow-up years 1-4. Using parallel process latent growth models, we found that childhood adversity was associated with increased risk for externalizing/internalizing behaviors. We specifically investigated whether functional connectivity of the dorsal anterior cingulate cortex (dACC) to brain regions within the cingulo-opercular (CO) network, a well-known EF network that underlies control of attention and self-regulation, mediates the association between adversity and symptoms of psychopathology. We found that childhood adversity, specifically child neglect was negatively associated with functional connectivity of the dACC within the CO network, and that this connectivity mediated the association between neglect and externalizing behaviors. Our study advances a mechanistic understanding of how childhood adversity may impact the development of psychopathology, highlighting the relevance of dACC functional networks particularly for externalizing psychopathology., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Driving under the influence of cannabis and alcohol represents a major safety concern due to the synergistic or additive effect of these substances of abuse. Hence, rapid road-site testing of these substances is highly desired to reduce risks of fatal accidents. Here we describe a wearable electrochemical sensing device for the simultaneous direct, decentralized, detection of salivary THC and alcohol. The new ring-based sensing platform contains a voltammetric THC sensor and an amperometric alcohol biosensor on the ring cap, along with the wireless electronics embedded within the ring case. Rapid replacement of the disposable sensing-electrode ring cap following each saliva assay is accomplished by aligning spring-loaded pins, mounted on the electronic board (PCB), with the current collectors of the sensing electrodes. The printed dual-analyte sensor ring cover is based on a MWCNT/carbon electrode for the THC detection along with a Prussian-blue transducer, coated with alcohol oxidase/chitosan reagent layer, for the biosensing of alcohol. THC and alcohol can thus be detected simultaneously in the same diluted saliva sample within 3 min, with no cross talk and no interferences from the saliva matrix. The new wearable ring sensor platform should enable law enforcement personnel to screen drivers in a single traffic stop and offers considerable promise for addressing growing concerns of drug-impaired driving., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The cerebellum is a target of alcoholism-related brain damage in adults, yet no study has prospectively tracked deviations from normal cerebellar growth trajectories in adolescents before and after initiating drinking., Methods: Magnetic resonance imaging tracked developmental volume trajectories of 10 cerebellar lobule and vermis tissue constituents in 548 no/low drinking youths age 12 to 21 years at induction into this 5-site, NCANDA (National Consortium on Alcohol and NeuroDevelopment in Adolescence) study. Over the 3- to 4-year longitudinal examination yielding 2043 magnetic resonance imaging scans, 328 youths remained no/low drinkers, whereas 220 initiated substantial drinking after initial neuroimaging., Results: Normal growth trajectories derived from no/low drinkers indicated that gray matter volumes of lobules V and VI, crus II, lobule VIIB, and lobule X declined faster with age in male youths than in female youths, whereas white matter volumes in crus I and crus II and lobules VIIIA and VIIIB expanded faster in female youths than in male youths; cerebrospinal fluid volume expanded faster in most cerebellar regions of male youths than female youths. Drinkers exhibited accelerated gray matter decline in anterior lobules and vermis, accelerated vermian white matter expansion, and accelerated cerebrospinal fluid volumes expansion of anterior lobules relative to youths who remained no/low drinkers. Analyses including both alcohol and marijuana did not support an independent role for marijuana in alcohol effects on cerebellar gray matter trajectories., Conclusions: Alcohol use-related cerebellar growth trajectory differences from normal involved anterior lobules and vermis of youths who initiated substantial drinking. These regions are commonly affected in alcohol-dependent adults, raising the possibility that cerebellar structures affected by youthful drinking may be vulnerable to age-alcohol interactions in later adulthood., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

How parents manifest symptoms of anxiety or depression may affect how children learn to modulate their own distress, thereby influencing the children's risk for developing an anxiety or mood disorder. Conversely, children's mental health symptoms may impact parents' experiences of negative emotions. Therefore, mental health symptoms can have bidirectional effects in parent-child relationships, particularly during moments of distress or frustration (e.g., when a parent or child makes a costly mistake). The present study used simultaneous functional magnetic resonance imaging (fMRI) of parent-adolescent dyads to examine how brain activity when responding to each other's costly errors (i.e., dyadic error processing) may be associated with symptoms of anxiety and depression. While undergoing simultaneous fMRI scans, healthy dyads completed a task involving feigned errors that indicated their family member made a costly mistake. Inter-brain, random-effects multivariate modeling revealed that parents who exhibited decreased medial prefrontal cortex and posterior cingulate cortex activation when viewing their child's costly error response had children with more symptoms of depression and anxiety. Adolescents with increased anterior insula activation when viewing a costly error made by their parent had more anxious parents. These results reveal cross-brain associations between mental health symptomatology and brain activity during parent-child dyadic error processing., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 d z  = 0.36) and medial prefrontal cortex (Cohen's d z  = 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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Relapse rates are consistently high for stimulant user disorders. In order to obtain prognostic information about individuals in treatment, machine learning models have been applied to neuroimaging and clinical data. Yet few efforts have been made to test these models in independent samples or show that they can outperform linear models. In this exploratory study, we examine whether machine learning models relative to linear models provide greater predictive accuracy and less overfitting., Method: This longitudinal study included 63 methamphetamine-dependent (training sample) and 29 cocaine-dependent (test sample) individuals who completed an MRI scan during residential treatment. Linear and machine learning models predicting relapse at a one-year follow up that were previously developed in the methamphetamine-dependent sample using neuroimaging and clinical variables were applied to the cocaine-dependent sample. Receiver operating characteristic analysis was used to assess performance using area under the curve (AUC) as the primary outcome., Results: Twelve individuals in the cocaine-dependent sample remained abstinent, and 17 relapsed. The linear models produced more accurate prediction in the training sample than the machine learning models but showed reduced performance in the testing sample, with AUC decreasing by 0.18. The machine learning models produced similar predictive performance in the training and test samples, with AUC changing by 0.03. In the test sample, neither the linear nor the machine learning model predicted relapse at rates above chance., Conclusions: Although machine learning algorithms may have advantages, in this study neither model's performance was sufficient to be clinically useful. In order to improve predictive models, stronger predictor variables and larger samples are needed., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Biospecimen collection in the Adolescent Brain Cognitive Development (ABCD) study - of hair samples, shed deciduous (baby) teeth, and body fluids - will serve dual functions of screening for study eligibility, and providing measures of biological processes thought to predict or correlate with key study outcomes on brain and cognitive development. Biosamples are being collected annually to screen for recency of drug use prior to the neuroimaging or cognitive testing visit, and to store for the following future studies: (1) on the effects of exposure to illicit and recreational drugs (including alcohol and nicotine); (2) of pubertal hormones on brain and cognitive developmental trajectories; (3) on the contribution of genomics and epigenomics to child and adolescent development and behavioral outcomes; and (4) with pre- and post-natal exposure to environmental neurotoxicants and drugs of abuse measured from novel tooth analyses. The present manuscript describes the rationales for inclusion and selection of the specific biospecimens, methodological considerations for each measure, future plans for assessment of biospecimens during follow-up visits, and preliminary ABCD data to illustrate methodological considerations., (Copyright © 2018. Published by Elsevier Ltd.)

The Adolescent Brain Cognitive Development (ABCD) study is designed to be the largest study of brain development and child health in the United States, performing comprehensive assessments of 11,500 children repeatedly for 10 years. An endeavor of this magnitude requires an organized framework of governance and communication that promotes collaborative decision-making and dissemination of information. The ABCD consortium structure, built upon the Matrix Management approach of organizational theory, facilitates the integration of input from all institutions, numerous internal workgroups and committees, federal partners, and external advisory groups to make use of a broad range of expertise to ensure the study's success., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

One of the objectives of the Adolescent Brain Cognitive Development (ABCD) Study (https://abcdstudy.org/) is to establish a national longitudinal cohort of 9 and 10 year olds that will be followed for 10 years in order to prospectively study the risk and protective factors influencing substance use and its consequences, examine the impact of substance use on neurocognitive, health and psychosocial outcomes, and to understand the relationship between substance use and psychopathology. This article provides an overview of the ABCD Study Substance Use Workgroup, provides the goals for the workgroup, rationale for the substance use battery, and includes details on the substance use module methods and measurement tools used during baseline, 6-month and 1-year follow-up assessment time-points. Prospective, longitudinal assessment of these substance use domains over a period of ten years in a nationwide sample of youth presents an unprecedented opportunity to further understand the timing and interactive relationships between substance use and neurocognitive, health, and psychopathology outcomes in youth living in the United States., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Retention efforts are critical to maintain relationships with research participants over time. This is especially important for the Adolescent Brain Cognitive Development (ABCD) study, where families are asked to stay engaged with the study throughout the course of 10 years. This high-degree of involvement is essential to longitudinally track child and adolescent development. At a minimum, we will connect with families every 6 months by telephone, and every year in person, with closer contact with the youth directly as they transition into adolescence. Differential retention, when related to non-random issues pertaining to demographic or risk features, can negatively impact the generalizability of study outcomes. Thus, to ensure high rates of retention for all participants, the ABCD study employs a number of efforts to support youth and families. This overview details the framework and concrete steps for retention., (Copyright © 2017. Published by Elsevier Ltd.)

The Adolescent Brain and Cognitive Development (ABCD) Study incorporates a comprehensive range of measures assessing predictors and outcomes related to both mental and physical health across childhood and adolescence. The workgroup developed a battery that would assess a comprehensive range of domains that address study aims while minimizing participant and family burden. We review the major considerations that went into deciding what constructs to cover in the demographics, physical health and mental health domains, as well as the process of selecting measures, piloting and refining the originally proposed battery. We present a description of the baseline battery, as well as the six-month interim assessments and the one-year follow-up assessments. This battery includes assessments from the perspectives of both the parent and the target youth, as well as teacher reports. This battery will provide a foundational baseline assessment of the youth's current function so as to permit characterization of stability and change in key domains over time. The findings from this battery will also be utilized to identify both resilience markers that predict healthy development and risk factors for later adverse outcomes in physical health, mental health, and substance use and abuse., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.)

Since the sample size of a typical neuroimaging study lacks sufficient statistical power to explore unknown genomic associations with brain phenotypes, several international genetic imaging consortia have been organized in recent years to pool data across sites. The challenges and achievements of these consortia are considered here with the goal of leveraging these resources to study addiction. The authors of this review have joined together to form an Addiction working group within the framework of the ENIGMA project, a meta-analytic approach to multisite genetic imaging data. Collectively, the Addiction working group possesses neuroimaging and genomic data obtained from over 10,000 subjects. The deadline for contributing data to the first round of analyses occurred at the beginning of May 2015. The studies performed on this data should significantly impact our understanding of the genetic and neurobiological basis of addiction., (© 2016 Elsevier B.V. All rights reserved.)

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.)

Background: Functional magnetic resonance imaging research suggests that major depressive disorder (MDD) in both adults and adolescents is marked by aberrant connectivity of the default mode network (DMN) during resting state. However, emotional dysregulation is also a key feature of MDD. No studies to date have examined emotion-related DMN pathology in adolescent depression. Comprehensively understanding the dynamics of DMN connectivity across brain states in individuals with depression with short disease histories could provide insight into the etiology of MDD., Methods: We collected functional magnetic resonance imaging data during an emotion identification task and during resting state from 26 medication-free adolescents (13-17 years old) with MDD and 37 well-matched healthy control subjects. We examined between-group differences in blood oxygenation level-dependent task responses and emotion-dependent and resting-state functional connectivity of the two primary nodes of the DMN: medial prefrontal cortex and posterior cingulate cortex (PCC). Additionally, we examined between-group differences in DMN functional connectivity and its relationship to depression severity and onset., Results: Relative to healthy control subjects, unmedicated adolescents with MDD demonstrated reduced medial prefrontal cortex and PCC emotion-related deactivation and greater medial prefrontal cortex and PCC emotion-dependent functional connectivity with precuneus, cingulate gyrus, and striatum/subcallosal cingulate gyrus. The PCC-subcallosal cingulate connectivity remained inflexibly elevated in the subjects with MDD versus healthy control subjects during resting state. Stronger PCC emotion-dependent functional connectivity was associated with greater depression severity and an earlier age of depression onset., Conclusions: Adolescent depression is associated with inflexibly elevated DMN connections. Given more recent evidence of DMN maturation throughout adolescence, our findings suggest that early-onset depression adversely affects normal development of functional brain networks., (Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Aims: Altered interoception, how the brain processes afferents from the body, may contribute to the urge to take drugs, and subsequently, the development of addiction. Although chronic stimulant dependent individuals exhibit attenuated brain responses to pleasant interoceptive stimuli, it is unclear whether this deficit exists early-on in the process of transition to stimulant addiction., Methods: To this end, we compared problem stimulant users (PSU; n=18), desisted stimulant users (DSU; n=15), and stimulant naïve comparison subjects (CTL; n=15) during functional magnetic resonance imaging (fMRI) while they anticipated and experienced pleasant soft touch (slow brushstroke to the palm and forearm)., Results: Groups did not differ in behavioral performance or visual analog scale ratings of soft touch stimuli. fMRI results indicated that PSU exhibited greater right anterior insula, left inferior frontal gyrus, and right superior frontal gyrus activation than DSU and CTL during the anticipation and experience of soft touch. Moreover, during the experience of soft touch, PSU demonstrated higher bilateral precentral gyrus/middle insula and right posterior temporal gyrus activation than DSU and CTL., Conclusions: In contrast to chronic stimulant dependence, individuals who have recently developed stimulant use disorders show exaggerated neural processing of pleasant interoceptive stimuli. Thus, increased processing of body-relevant information signaling pleasant touch in those individuals who develop problem use may be a predictive interoceptive biomarker. However, future investigations will need to determine whether the combination of probing pleasant interoception using neuroimaging is sufficiently sensitive and specific to help identify individuals at high risk for future problem use., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Nearly half of individuals with substance use disorders relapse in the year after treatment. A diagnostic tool to help clinicians make decisions regarding treatment does not exist for psychiatric conditions. Identifying individuals with high risk for relapse to substance use following abstinence has profound clinical consequences. This study aimed to develop neuroimaging as a robust tool to predict relapse., Methods: 68 methamphetamine-dependent adults (15 female) were recruited from 28-day inpatient treatment. During treatment, participants completed a functional MRI scan that examined brain activation during reward processing. Patients were followed 1 year later to assess abstinence. We examined brain activation during reward processing between relapsing and abstaining individuals and employed three random forest prediction models (clinical and personality measures, neuroimaging measures, a combined model) to generate predictions for each participant regarding their relapse likelihood., Results: 18 individuals relapsed. There were significant group by reward-size interactions for neural activation in the left insula and right striatum for rewards. Abstaining individuals showed increased activation for large, risky relative to small, safe rewards, whereas relapsing individuals failed to show differential activation between reward types. All three random forest models yielded good test characteristics such that a positive test for relapse yielded a likelihood ratio 2.63, whereas a negative test had a likelihood ratio of 0.48., Conclusions: These findings suggest that neuroimaging can be developed in combination with other measures as an instrument to predict relapse, advancing tools providers can use to make decisions about individualized treatment of substance use disorders., (Published by Elsevier Ireland Ltd.)

Background: Drug dependent individuals often make drug-taking decisions when they do not feel well. Yet, few studies have examined the influence of an aversive state on decision-making related neural processing., Methods: We investigate brain activation to decision-making during an aversive interoceptive challenge in methamphetamine users using functional magnetic resonance imaging (fMRI). Recently abstinent inpatients with methamphetamine use disorder (METH; n=20) and healthy comparison subjects (CTL; n=22) performed a two-choice prediction task at three fixed error rates (ER; 20%=reward, 50%=uncertainty, 80%=punishment) while anticipating and experiencing episodes of inspiratory breathing load during fMRI., Results: METH exhibited higher trait anxiety in conjunction with lower anterior insula (AI) and inferior frontal gyrus (IFG) activation than CTL across trials. METH also showed lower posterior insula (PI) and anterior cingulate cortex (ACC) activation than CTL during breathing load independent of ER. For the crucial ER by interoception interaction, METH displayed lower ACC activation to punishment/loss than CTL during breathing load. Within METH, lower trait anxiety was linked to AI/IFG attenuation across trials., Conclusions: AI/IFG attenuations in METH are suggestive of an executive functioning deficit, particularly in users with low anxiety, reflecting reduced resources allocated to choice selection. In contrast, PI/ACC reductions in METH appear specific to impairments in registering and evaluating interoceptive experiences. Taken together, inadequate activation of brain areas that are important for regulating when one does not feel well may be the neural basis for poor decision-making by METH., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Brain abnormalities in adolescent heavy drinkers may result from alcohol exposure, or stem from pre-existing neural features., Methods: This longitudinal morphometric study investigated 40 healthy adolescents, ages 12-17 at study entry, half of whom (n=20) initiated heavy drinking over the 3-year follow-up. Both assessments included high-resolution magnetic resonance imaging. FreeSurfer was used to segment brain volumes, which were measured longitudinally using the newly developed quantitative anatomic regional change analysis (QUARC) tool., Results: At baseline, participants who later transitioned into heavy drinking showed smaller left cingulate, pars triangularis, and rostral anterior cingulate volume, and less right cerebellar white matter volumes (p<.05), compared to continuous non-using teens. Over time, participants who initiated heavy drinking showed significantly greater volume reduction in the left ventral diencephalon, left inferior and middle temporal gyrus, and left caudate and brain stem, compared to substance-naïve youth (p<.05)., Conclusion: Findings suggest pre-existing volume differences in frontal brain regions in future drinkers and greater brain volume reduction in subcortical and temporal regions after alcohol use was initiated. This is consistent with literature showing pre-existing cognitive deficits on tasks recruited by frontal regions, as well as post-drinking consequences on brain regions involved in language and spatial tasks., (Published by Elsevier Ltd.)

Background: Although the interaction of brain volume with amphetamine-type stimulants (ATS) and cocaine has been investigated in chronically dependent individuals, little is known about structural differences that might exist in individuals who consume ATS and cocaine occasionally but are not dependent on these drugs., Methods: Regional brain volumes in 165 college aged occasional users of ATS (namely: amphetamine, methamphetamine, methylphenidate, and 3,4-methylenedioxymethamphetamine; MDMA) and cocaine were compared by voxel-based morphometry with 48 ATS/cocaine-naive controls., Results: Grey matter volume was significantly higher in the left ventral anterior putamen of occasional users, and lower in the right dorsolateral cerebellum and right inferior parietal cortex. A regression in users alone on lifetime consumption of combined ATS (namely: amphetamine, methamphetamine, methylphenidate and MDMA) and cocaine use revealed that individuals who used more ATS/cocaine had greater volume in the right ventromedial frontal cortex. A second regression on lifetime consumption of ATS with cocaine as a covariate revealed that individuals with a greater history of ATS use alone had more grey matter volume in the left mid-insula. Interestingly, structural changes in the ventromedial prefrontal cortex, insula and striatum have been consistently observed in volumetric studies of chronic ATS and cocaine dependence., Conclusion: The present results suggest that these three brain regions may play a role in stimulant use even in early occasional users., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

This article reviews the neurocognitive and neuroimaging literature regarding the effect of alcohol use on human adolescent brain structure and function. Adolescents who engage in heavy alcohol use, even at subdiagnostic levels, show differences in brain structure, function, and behavior when compared with non-drinking controls. Preliminary longitudinal studies have helped disentangle premorbid factors from consequences associated with drinking. Neural abnormalities and cognitive disadvantages both appear to predate drinking, particularly in youth who have a family history of alcoholism, and are directly related to the neurotoxic effect of alcohol use. Binge drinking and withdrawal and hangover symptoms have been associated with the greatest neural abnormalities during adolescence, particularly in frontal, parietal, and temporal regions., (© 2014 Elsevier B.V. All rights reserved.)

Background: Very few studies have been performed to understand the underlying neural substrates of adolescent major depressive disorder (MDD). Studies in depressed adults have demonstrated that the subgenual anterior cingulate cortex (sgACC) plays a pivotal role in depression and have revealed aberrant patterns of resting-state functional connectivity (RSFC). Here, we examine the RSFC of the sgACC in medication-naïve first-episode adolescents with MDD., Methods: Twenty-three adolescents with MDD and 36 well-matched control subjects underwent functional magnetic resonance imaging to assess the RSFC of the sgACC., Results: We observed elevated connectivity between the sgACC and the insula and between the sgACC and the amygdala in the MDD group compared with the control subjects. Decreased connectivity between the sgACC and the precuneus was also found in the MDD group relative to the control subjects. Within the MDD group, higher levels of depression significantly correlated with decreased connectivity between the sgACC and left precuneus. Increased rumination was significantly associated with reduced connectivity between sgACC and the middle and inferior frontal gyri in the MDD group., Conclusions: Our study is the first to examine sgACC connectivity in medication-naïve first-episode adolescents with MDD compared with well-matched control participants. Our results suggest aberrant functional connectivity among the brain networks responsible for salience attribution, executive control, and the resting-state in the MDD group compared with the control participants. Our findings raise the possibility that therapeutic interventions that can restore the functional connectivity among these networks to that typical of healthy adolescents might be a fruitful avenue for future research., (Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

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.)

Background: Attention-deficit/hyperactivity disorder (ADHD) and cannabis use are each associated with specific cognitive deficits. Few studies have investigated the neurocognitive profile of individuals with both an ADHD history and regular cannabis use. The greatest cognitive impairment is expected among ADHD Cannabis Users compared to those with ADHD-only, Cannabis use-only, or neither., Methods: Young adults (24.2 ± 1.2 years) with a childhood ADHD diagnosis who did (n=42) and did not (n=45) report past year ≥ monthly cannabis use were compared on neuropsychological measures to a local normative comparison group (LNCG) who did (n=20) and did not (n=21) report past year regular cannabis use. Age, gender, IQ, socioeconomic status, and past year alcohol and smoking were statistical covariates., Results: The ADHD group performed worse than LNCG on verbal memory, processing speed, cognitive interference, decision-making, working memory, and response inhibition. No significant effects for cannabis use emerged. Interactions between ADHD and cannabis were non-significant. Exploratory analyses revealed that individuals who began using cannabis regularly before age 16 (n=27) may have poorer executive functioning (i.e., decision-making, working memory, and response inhibition), than users who began later (n=32); replication is warranted with a larger sample., Conclusions: A childhood diagnosis of ADHD, but not cannabis use in adulthood, was associated with executive dysfunction. Earlier initiation of cannabis use may be linked to poor cognitive outcomes and a significantly greater proportion of the ADHD group began using cannabis before age 16. Regular cannabis use starting after age 16 may not be sufficient to aggravate longstanding cognitive deficits characteristic of ADHD., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: Although substantial literature has reported regional cerebral blood flow (rCBF) abnormalities in adults with depression, these studies commonly necessitated the injection of radioisotopes into subjects. The recent development of arterial spin labeling (ASL), however, allows noninvasive measurements of rCBF. Currently, no published ASL studies have examined cerebral perfusion in adolescents with depression. Thus, the aim of the present study was to examine baseline cerebral perfusion in adolescent depression using a newly developed ASL technique: pseudocontinuous arterial spin labeling (PCASL)., Method: A total of 25 medication-naive adolescents (13-17 years of age) diagnosed with major depressive disorder (MDD) and 26 well-matched control subjects underwent functional magnetic resonance imaging. Baseline rCBF was measured via a novel PCASL method that optimizes tagging efficiency., Results: Voxel-based whole brain analyses revealed significant frontal, limbic, paralimbic, and cingulate hypoperfusion in the group with depression (p < .05, corrected). Hyperperfusion was also observed within the subcallosal cingulate, putamen, and fusiform gyrus (p < .05, corrected). Similarly, region-of-interest analyses revealed amygdalar and insular hypoperfusion in the group with depression, as well as hyperperfusion in the putamen and superior insula (p < .05, corrected)., Conclusions: Adolescents with depression and healthy adolescents appear to differ on rCBF in executive, affective, and motor networks. Dysfunction in these regions may contribute to the cognitive, emotional, and psychomotor symptoms commonly present in adolescent depression. These findings point to possible biomarkers for adolescent depression that could inform early interventions and treatments, and establishes a methodology for using PCASL to noninvasively measure rCBF in clinical and healthy adolescent populations., (Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Mechano-receptive C-fiber (MR-CF) stimulation via slow stroking of C-fiber rich skin areas can be used to probe the relationship between reward and interoception. Individuals with substance use disorders show impaired reward processing, and dysfunctional interoceptive processing of MR-CF may contribute to this dysfunction. This study predicted that methamphetamine dependent (MD) individuals would exhibit altered responses to MR-CF stimulation in brain regions important for interoception., Methods: Recently abstinent MD (n=25) and comparison (CTL, n=17) subjects received a pleasant interoceptive stimulus ("Soft Touch" consisting of a slow brush stroke) to the palm or forearm during functional magnetic resonance imaging. Subjects were provided with cues signaling stimulation to examine anticipatory and stimulus-related processing. Subjective responses were measured using visual analog scales (VAS)., Results: Groups were similar on behavioral performance and ratings of the interoceptive stimuli, yet MD exhibited lower anterior insula, dorsal striatum, and thalamus activation than CTL, across anticipation and soft touch conditions. The lower the anterior insula activation, the faster the reaction time across conditions in MD, whereas the opposite pattern was evident in CTL. Striatal activation in MD was greater than CTL during anticipation, but lower during soft touch. Greater striatal attenuation was associated with higher VAS pleasantness ratings of soft touch., Conclusions: MD expend fewer brain processing resources during soft touch, a form of positively-valenced interoceptive stimuli, in brain areas that are important for both interoception and reward. Future studies will ascertain if sustained abstinence from methamphetamine use can normalize aberrant neural interoceptive processing., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Alcohol-induced blackouts are associated with the development of alcohol abuse and dependence, so it is important to consider potential neurobiological risk factors for experiencing this problem prior to the onset of substance use. This study examines whether neural activity during inhibitory processing might be atypical in substance-naïve youth who later experience alcohol-induced blackouts., Methods: We examined inhibitory processing during fMRI with a go/no-go task that requires withholding a prepotent response in substance-naïve youth who would later transition into heavy drinking (n=40) and youth who remain abstinent (n=20). After approximately 5 years of annual follow-up assessments, youth were classified as nondrinkers (n=20), and heavy drinking youth were classified as having experienced an alcohol-induced blackout (blackout+; n=20) or not (blackout-; n=20). Groups were matched on demographic variables, and youth who experienced blackouts were matched on follow-up substance use., Results: Prior to initiating substance use, blackout+ youth showed greater activation during inhibitory processing than nondrinkers and blackout- youth in frontal and cerebellar brain regions. Mean activation during correct inhibitory responses relative to go responses in the left and right middle frontal gyri at baseline predicted future blackout experience, after controlling for follow-up externalizing behaviors and lifetime alcohol consumption., Conclusions: Substance-naïve adolescents who later experience alcohol-induced blackouts show increased neural effort during inhibitory processing, as compared to adolescents who go on to drink at similar levels but do not experience blackouts and healthy, nondrinking controls, suggesting a neurobiological vulnerability to alcohol-induced memory impairments., (Published by Elsevier Ireland Ltd.)