Norma Castro

Brain volume reductions in adolescent heavy drinkers.

Highlights • Pre-existing frontal brain volume differences were found in future drinkers.• Adolescent drinkers showed greater brain volume reduction post-alcohol initiation.• Volume reduction occurred in subcortical and temporal regions.• QUARC is a useful tool for quantifying longitudinal brain volume changes.

Atypical neural activity during inhibitory processing in substance-naïve youth who later experience alcohol-induced blackouts

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.

Cortical thickness in adolescent marijuana and alcohol users: A three-year prospective study from adolescence to young adulthood

Highlights • . Adolescent marijuana and alcohol users show thicker cortices compared to controls.• More cumulative marijuana use is associated with increased cortical thickness.• More cumulative alcohol use is associated with decreased cortical thickness.• Regular marijuana and alcohol use may have a deleterious impact on adolescent brain development.

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.

BOLD response to working memory not related to cortical thickness during early adolescence.

BACKGROUND Significant cortical thinning and neural resource allocation changes emerge during adolescence; however, little is known of how morphometric changes influence neural response to cognitive demands. This study used a novel multimodal imaging registration technique to examine the relationship between brain structure and function during adolescence. METHODS 156 healthy 12-14 year-olds (44% female) participants underwent structural and functional magnetic resonance imaging. Cortical surface reconstruction was performed via FreeSurfer, and neural activation was measured from a blood oxygen level dependent (BOLD) contrast during visual working memory (VWM) via AFNI. AFNI Surface Mapper aligned segmented volumetric and functional datasets to a common template space. Hierarchical linear regressions determined the effect of cortical thickness on VWM BOLD contrast in brain regions that activated during the VWM task, controlling for age, pubertal development, gender, IQ, and intracranial volume. RESULTS Power analyses suggest this study was able to detect small effect sizes. However, in no region was cortical thickness related to BOLD activation (ps>.01; R(2)Δ<.02). Gender did not moderate effects. CONCLUSIONS Cortical thickness, although variable across individuals, was not related to BOLD response, suggesting that structural and functional maturation do not have the same developmental trajectory during early adolescence. These findings are important, as imaging studies that report group differences in regards to cortical thickness should not necessarily assume co-occurring behavioral or functional changes. The methodology used in this study could be of interest to other developmental neuroimaging researchers using multimodal imaging to understand adolescent brain development.

Cannabis and alcohol use, and the developing brain

Abstract Sex hormones and white (and grey) matter in the limbic system, cortex and other brain regions undergo changes during adolescence. Some of these changes include ongoing white matter myelination and sexually dimorphic features in grey and white matter. Adolescence is also a period of vulnerability when many are first exposed to alcohol and cannabis, which appear to influence the developing brain. Neuropsychological studies have provided considerable understanding of the effects of alcohol and cannabis on the brain. Advances in neuroimaging have allowed examination of neuroanatomic changes, metabolic and neurotransmitter activity, and neuronal activation during adolescent brain development and substance use. In this review, we examine major differences in brain development between users and non‐users, and recent findings on the influence of cannabis and alcohol on the adolescent brain. We also discuss associations that appear to resolve following short‐term abstinence, and attentional deficits that appear to persist. These findings can be useful in guiding earlier educational interventions for adolescents, and clarifying the neural sequelae of early alcohol and cannabis use to the general public.

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.

Effects of Marijuana Use on Brain Structure and Function: Neuroimaging Findings from a Neurodevelopmental Perspective

Marijuana, behind only tobacco and alcohol, is the most popular recreational drug in America with prevalence rates of use rising over the past decade. A wide range of research has highlighted neurocognitive deficits associated with marijuana use, particularly when initiated during childhood or adolescence. Neuroimaging, describing alterations to brain structure and function, has begun to provide a picture of possible mechanisms associated with the deleterious effects of marijuana use. This chapter provides a neurodevelopmental framework from which recent data on brain structural and functional abnormalities associated with marijuana use is reviewed. Based on the current data, we provide aims for future studies to more clearly delineate the effects of marijuana on the developing brain and to define underlying mechanisms of the potential long-term negative consequences of marijuana use.

A multi-site proof-of-concept investigation of computerized approach-avoidance training in adolescent cannabis users*

BACKGROUND Few effective treatment options exist for cannabis-using youth. This pilot study aimed to test Approach-Avoidance Training to reduce cannabis use with non-treatment-seeking adolescents. METHODS Eighty cannabis-using non-treatment-seeking adolescents (average age 19) were recruited from San Diego, California and Charleston, South Carolina, and randomized to complete either six sessions of Cannabis Approach-Avoidance Task Training (CAAT-training) designed to reduce automatic approach biases for cannabis cues or CAAT-sham training. Change in two primary outcome variables was examined: 1) cannabis approach bias and 2) percent cannabis use days over study enrollment. Change in percent alcohol use days over study enrollment was explored as a secondary outcome. RESULTS A mixed models repeated measures analysis confirmed the group by time interaction effect for approach bias failed to reach statistical significance (p = .06). Significant group by time interaction effects (ps < 0.05) predicted percent days of cannabis and alcohol use over study enrollment. Participants randomized to the avoid cannabis condition (CAAT-training) reported 7% fewer days of cannabis use compared to 0% change for sham; unexpectedly, those in the avoid cannabis condition reported 10% percent more alcohol use days compared to 3% more for sham. CONCLUSIONS Computerized cognitive bias modification paradigms may have utility in reducing adolescent cannabis use. Future work should consider developing a paradigm that addresses both cannabis and alcohol, as well as alternative computerized approaches for coping with addictive behavior in conjunction with bias modification.

The effects of alcohol hangover on future drinking behavior and the development of alcohol problems

INTRODUCTION Alcohol hangover experiences in young adulthood have been shown to predict more subsequent alcohol problems. Hangover susceptibility appears to be partially heritable and related to family history of alcohol use disorders. However, very little is known about the developmental course of these associations and whether they are accounted for by an individuals drinking history. The goal of this study is to investigate the prospective and unique relationships between family history of alcohol use disorders, severity of alcohol hangover experiences in adolescence, and later alcohol use and related problems measured over 13years. METHODS Participants were first assessed on family history at age 12-14, prior to initiating drinking, and re-assessed annually on hangover severity, drinks per drinking day (DPDD), and alcohol-related problems throughout the 13-year follow-up period (n=205; 59% male). RESULTS In mixed effects negative binomial regression models, greater family history density scores predicted more future DPDD (Incidence Rate Ratio [IRR]=1.19, p=0.04), alcohol problems (IRR=1.64, p=0.05), and future hangover severity (IRR=1.24; p=0.01). In turn, greater hangover severity predicted more future DPDD (IRR=1.03; p=0.002) and alcohol problems (IRR=1.12, p<0.001), and hangover severity mediated the relationship between family history and alcohol use/problems. All models controlled for participant age, sex, and past drinking behavior (where relevant). CONCLUSIONS These results advance the alcohol hangover experience during late adolescence as a clinically relevant and uniquely informative marker of future alcohol use and problems, above and beyond that of prior personal or familial drinking history.