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 individual's 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.

Objective

Changes in gray matter volume and thickness are associated with adolescent alcohol and cannabis use, but the impact of these substances on surface area remains unclear. The present study expands on previous findings to examine the impact of alcohol and cannabis on surface area before and after use initiation.

Method

Scans for 69 demographically similar youth were obtained at baseline (ages 12-14 years; before substance use) and at 6-year follow-up (ages 17-21 years). Participants were classified into three groups based on substance use: alcohol use initiators (ALC, n = 23), alcohol and cannabis use initiators (ALC+CU, n = 23), and individuals with minimal substance use (<3 lifetime alcohol and 0 marijuana use episodes; CON, n = 23). For each hemisphere, group differences in surface area across time (pre- and post-substance use initiation) and significant group-by-time interactions were examined individually for 34 cortical regions using repeated measures analysis of covariance. A vertex-wise analysis assessed group differences in surface area percent change.

Results

A significant group-by-time interaction was found in three regions, bilateral medial orbitofrontal cortices and right insula. Although all regions showed decreases in surface area over time (ps < .05), a more substantial decrease was identified in the ALC group. Of note, the right medial orbitofrontal cortex survived the conservative vertex-wise analyses (p < .001), as a more substantial decrease was found in the ALC compared to the ALC+CU group in this region.

Conclusions

Surface area in the medial orbitofrontal cortex may be a useful intermediate phenotype for exploring the mechanisms underlying the effects of substance use on brain development.

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

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.

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.

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.

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.

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 (β = -.15) and visuospatial ability (β = -.19). More postdrinking effects (β = -.15) and greater drug use (β = -.11) predicted worse psychomotor speed. Processing speed was not predicted by substance involvement (ps > .05). Unexpectedly, more alcohol use predicted better working memory performance (β = .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.

Background

Neurodevelopment may be shaped by environmental factors such as alcohol intake. Over 20% of U.S. high school students begin drinking before age 14, and those who initiated drinking before age 14 are 4 times more likely to develop psychosocial, psychiatric, and substance use difficulties than those who began drinking after turning 20. Little is known, however, about how the age of alcohol use onset influences brain development.

Methods

This study prospectively examined the effects of alcohol use onset age on neurocognitive functioning in healthy adolescent drinkers (N = 215). Youth were administered a neuropsychological battery before substance use initiation (M = 13.6 years, SD = 0.8) and on average 6.8 years later (M = 20.2 years, SD = 1.5). Hierarchical linear regressions examined if earlier ages of onset for first and regular (i.e., weekly) alcohol use adversely influenced neurocognition, above and beyond baseline neurocognition, substance use severity, and familial and social environment factors.

Results

As hypothesized, an earlier age of first drinking onset (AFDO) predicted poorer performance in the domains of psychomotor speed and visual attention (ps<0.05, N = 215) and an earlier age of weekly drinking onset (AWDO) predicted poorer performances on tests of cognitive inhibition and working memory, controlling for baseline neuropsychological performance, drinking duration, and past-year marijuana use (ps<0.05, N = 127). No relationship between AFDO and AWDO was found with verbal learning and memory and visuospatial ability.

Conclusions

This is the first study to assess the association between age of adolescent drinking onset and neurocognitive performance using a comprehensive test battery. This study suggests that early onset of drinking increases risk for alcohol-related neurocognitive vulnerabilities and that initiation of any or weekly alcohol use at younger ages appears to be a risk factor for poorer subsequent neuropsychological functioning. Findings have important implications for public policies related to the legal drinking age and prevention programming. Further studies are needed to replicate these preliminary findings and better understand mediating processes and moderating conditions.

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.