Background Adolescence is a period in which cognition and brain undergo dramatic parallel development. Whereas chronic use of alcohol and marijuana is known to cause cognitive impairments in adults, far less is known about the effect of these substances of abuse on adolescent cognition, including possible interactions with developmental processes. Methods Neuropsychological performance, alcohol use, and marijuana use were assessed in 48 adolescents (ages 12–18), recruited in three groups: a healthy control group (HC, n = 15), a group diagnosed with substance abuse or dependence (SUD, n = 19), and a group with a family history positive for alcohol use disorder (AUD) but no personal substance use disorder (FHP, n = 14). Age, drinks per drinking day, percentage days drinking, and percentage days using marijuana were considered as covariates in a MANCOVA in which 6 neuropsychological composites (Verbal Reasoning, Visuospatial Ability, Executive Function, Memory, Attention, and Processing Speed) served as dependent variables. Results More drinks per drinking day predicted poorer performance on Attention and Executive Function composites, and more frequent use of marijuana use was associated with poorer Memory performance. In separate analyses, adolescents in the SUD group had lower scores on Attention, Memory, and Processing Speed composites, and FHP adolescents had poorer Visuospatial Ability. Conclusions In combination, these analyses suggest that heavy alcohol use in adolescence leads to reduction in attention and executive functioning and that marijuana use exerts an independent deleterious effect on memory. At the same time, premorbid deficits associated with family history of AUD appeared to be specific to Visuospatial Ability.

Atrophy of brain white matter (WM) often is considered a signature injury of alcohol use disorders (AUDs). However, investigations into AUD-related changes in WM volume have yielded complex findings that are difficult to synthesize in a narrative review. The objective of this study was to obtain an averaged effect size (ES) for WM volume reduction associated with AUD diagnosis and to test potential moderators of ES. Study inclusion criteria were: 1) English language; 2) peer-reviewed; 3) published before December 2011; 4) use of MRI; 5) human participants; 6) inclusion of AUD group; 7) inclusion of non-AUD comparison group; 8) reporting or testing of total or cerebral WM volume. Moderators included study design, MRI methodology, and AUD characteristics. Nineteen studies with a total of 1,302 participants (70% male) were included, and calculated ES were confirmed by the corresponding author for 12 studies. The magnitude of the averaged ES adjusted for small sample bias (Hedges’ g) for WM reduction in AUDs was .304 (standard error = .134, range = −.57–1.21). Hierarchical linear modeling indicated that the overall ES differed significantly from 0, t(18) = 2.257, p = .037, and that the distribution of the 19 ES showed significant heterogeneity beyond sampling error, χ2(18) = 52.400, p < .001. Treatment-seeking status and length of abstinence were significant moderators of ES distribution. These results are suggestive of WM recovery with sustained abstinence and point to the need for further investigation of factors related to treatment-seeking status.

Prescription psychostimulants produce rapid changes in mood, energy, and attention. These drugs are widely used and abused. However, their effects in human neocortex on glutamate and glutamine (pooled as Glx), and key neurometabolites such as N-acetylaspartate (tNAA), creatine (tCr), choline (Cho), and myo-inositol (Ins) are poorly understood. Changes in these compounds could inform the mechanism of action of psychostimulant drugs and their abuse potential in humans. We investigated the acute impact of two FDA-approved psychostimulant drugs on neurometabolites using magnetic resonance spectroscopy (H MRS). Single clinically relevant doses of d-amphetamine (AMP, 20 mg oral), methamphetamine (MA, 20 mg oral; Desoxyn®), or placebo were administered to healthy participants (n = 26) on three separate test days in a placebo-controlled, double-blinded, within-subjects crossover design. Each participant experienced all three conditions and thus served as his/her own control. H MRS was conducted in the dorsal anterior cingulate cortex (dACC), an integrative neocortical hub, during the peak period of drug responses (140-150 m post ingestion). D-amphetamine increased the level of Glu (p = .0001), Glx (p = .003), and tCr (p = .0067) in the dACC. Methamphetamine increased Glu in females, producing a significant crossover interaction pattern with gender (p = .02). Drug effects on Glu, tCr, and Glx were positively correlated with subjective drug responses, predicting both the duration of AMP liking (Glu: r = +.49, p = .02; tCr: r = +.41, p = .047) and the magnitude of peak drug high to MA (Glu: r = +.52, p = .016; Glx: r = +.42, p = .049). Neither drug affected the levels of tNAA, Cho, or Ins after correction for multiple comparisons. We conclude that d-amphetamine increased the concentration of glutamate, Glx, and tCr in the dACC in male and female volunteers 2/ hours after drug consumption. There was evidence that methamphetamine differentially affects dACC Glu levels in women and men. These findings provide the first experimental evidence that specific psychostimulants increase the level of glutamatergic compounds in the human brain, and that glutamatergic changes predict the extent and magnitude of subjective responses to psychostimulants.

As acute ethanol exposure inhibits N-methyl-D-aspartate glutamate (Glu) receptors, sudden withdrawal from chronic alcohol use may lead to an increased activation of these receptors with excitotoxic effects. In the longer term, brain levels of Glu and its metabolites, such as glutamine (Gln), are likely to be chronically altered by alcohol, possibly providing a measure of overall abnormal Glu-Gln cycling. However, few studies have assessed concentrations of these metabolites in clinical populations of individuals with alcohol use disorders. Glu and Gln levels were compared in groups of 17 healthy controls and in 13 participants with alcohol dependence. Within the alcohol-dependent group, seven participants had current alcohol use disorder (AUD), and six had AUD in remission for at least 1 year (AUD-R). Neurometabolite concentrations were measured with proton magnetic resonance spectroscopy ((1)H-MRS) in a predominantly gray matter voxel that included the bilateral anterior cingulate gyri. Tissue segmentation provided an assessment of the proportion of gray matter in the (1)H-MRS voxel. The Drinker Inventory of Consequences (DrInC) and Form-90 were administered to all participants to quantify alcohol consequences and use. Glu level was lower and Gln level was higher in the AUD and AUD-R groups relative to the control group; creatine, choline, myo-inositol, and total N-acetyl groups, primarily N-acetylaspartate did not differ across groups. These results were not confounded by age, sex, or proportion of gray matter in the (1)H-MRS voxel. Neurometabolite concentrations did not differ between AUD and AUD-R groups. Subsequent regressions in the combined clinical group, treating voxel gray matter proportion as a covariate, revealed that total score on the DrInC was positively correlated with Gln but negatively correlated with both Glu and gray matter proportion. Regression analyses, including DrInC scores and smoking variables, identified a marginal independent effect of smoking on Gln. The current findings of higher Gln and lower Glu in the combined AUD and AUD-R groups might indicate a perturbation of the Glu-Gln cycle in alcohol use disorders. The absence of differences in mean Glu and Gln between the AUD and AUD-R groups suggests that altered Glu-Gln metabolism may either predate the onset of abuse or persist during prolonged abstinence.

Individuals with alcohol use disorders show white matter abnormality relative to normal samples, yet differences in white matter profiles have not yet been investigated as a function of abstinence. Individuals with current alcohol use disorders (AUD-C; n = 10), individuals with alcohol use disorders in remission for at least one year (AUD-R; n = 9), and healthy control participants (HC; n = 15) matched to alcohol groups on age and smoking status underwent magnetic resonance imaging (MRI). Diffusion tensor imaging (DTI) data were analyzed using tract-based spatial statistics (TBSS). Compared to HC, AUD-C showed reduced axial diffusivity in bilateral frontal and temporal white matter. In AUD-R, lower fractional anisotropy relative to HC was widespread in bilateral parietal regions. A combined AUD-C and AUD-R group had decreased fractional anisotropy primarily in the fornix and thalamus. In conclusion, AUD-R manifested damage in parietal regions integral to processing of visuospatial information and self-awareness, whereas AUD-C showed abnormal diffusivity in fronto-temporal regions that regulate impulsivity, attention, and memory. As a combined group, AUD individuals exhibited abnormality in subcortical areas associated with sensory processing and memory. White matter differences in individuals with AUD may be attributable to premorbid vulnerability or persisting effects of alcohol abuse, but the pattern of abnormality across groups suggests that these abnormalities may be secondary to alcohol use.

Damage to the brain’s white matter is a signature injury of alcohol use disorders (AUDs), yet understanding of risks associated with clinical and demographic characteristics is incomplete. This study investigated alcohol problem severity, recent drinking behavior, and demographic factors in relation to white matter microstructure in heavy drinkers. Magnetic resonance imaging (MRI) scans, including diffusion tensor imaging (DTI), were collected from 324 participants (mean age = 30.9 ± 9.1 years; 30% female) who reported five or more heavy drinking episodes in the past 30 days. Drinking history and alcohol problem severity were assessed. A common white matter factor was created from fractional anisotropy (FA) values of five white matter tracts: body of corpus callosum, fornix, external capsule, superior longitudinal fasciculus, and cingulate gyrus. Previous research has implicated these tracts in heavy drinking. Structural equation modeling (SEM) analyses tested the hypothesis that, after controlling for duration of alcohol exposure, clinical and behavioral measures of alcohol use severity would be associated with lower white matter factor scores. Potential interactions with smoking status, gender, age, treatment-seeking status, and depression or anxiety symptoms also were tested. Controlling for number of years drinking, greater alcohol problem severity and recent drinking frequency were significantly associated with lower white matter factor scores. The effect of drinking frequency differed significantly for men and women, such that higher drinking frequency was linked to lower white matter factor scores in women but not in men. In conclusion, alcohol problem severity was a significant predictor of lower white matter FA in heavy drinkers, after controlling for duration of alcohol exposure. In addition, more frequent drinking contributed to lower FA in women but not men, suggesting gender-specific vulnerability to alcohol neurotoxicity.

Previous studies of schizophrenia have suggested a linkage between neuropsychological (NP) deficits and hippocampus abnormality. The relationship between hippocampus volume and NP functioning was investigated in 24 patients with chronic schizophrenia and 24 matched healthy controls. Overall intracranial, white and gray matter, and anterior (AH) and posterior (PH) hippocampus volumes were assessed from magnetic resonance images (MRI). NP domains of IQ, attention, and executive function were also evaluated with respect to volumetric measures. It was hypothesized that AH and PH volumes and episodic memory scores would be positively associated in controls and that the schizophrenia group would depart from this normative pattern. NP functioning was impaired overall and AH volume was smaller in the schizophrenia group. In the controls, the hippocampus-memory relationships involved AH and PH, and correlations were significant for verbal memory measures. In the schizophrenia group, positive correlations were constrained to PH. Negative correlations emerged between AH and verbal and visual memory measures. For both groups, cortical volume negatively correlated with age, but a negative correlation between age and hippocampus volume was found only in the schizophrenia group. In this sample of adults with schizophrenia, atypical relationships between regional hippocampus volumes and episodic memory ability were found, as was an atypical negative association between hippocampus volume and age.

Alcohol-related blackouts are common among college student drinkers. The present study extends prior work by examining latent growth classes of blackouts and several predictors of class membership. Participants (N=709 college drinkers) completed a baseline survey at college entry and biweekly online assessments throughout freshman and sophomore years. Results revealed five latent growth class trajectories, reflecting varying experiences of blackouts at the beginning of college and differential change in blackouts over time. The largest class represented a relatively low risk group (LOW DECR; 47.3%) characterized by endorsement of no or very low likelihood of blackouts, and decreasing likelihood of blackouts over time. Another decreasing risk group (HIGH DECR; 11.1%) initially reported a high proportion of blackouts and had the steepest decrease in blackout risk over time. A small percentage showed consistently high likelihood of blackouts over time (HIGH STABLE; 4.1%). The remaining two groups were distinguished by relatively moderate (MOD STABLE; 14.9%) and lower (LOW STABLE; 22.6%) likelihood of blackouts, which remained stable over time. Comparisons between classes revealed that students with greater perceived peer drinking, perceived peer approval of drinking, and enhancement motives upon entry to college tended to be in higher-risk groups with consistent experiences of blackouts over time, whereas blackout likelihood decreased over time for students with greater conformity motives. Findings suggest that pre-college preventive interventions may be strengthened by considering not only factors related to current risk for blackouts and other alcohol-related consequences, but also those factors related to persistence of these behaviors over time.