Mollie A. Monnig

Adolescent Substance Abuse: The Effects of Alcohol and Marijuana on Neuropsychological Performance

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 to 18), recruited in 3 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 (DPDD), 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 DPDD predicted poorer performance on Attention and Executive Function composites, and more frequent use of marijuana 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.

Perturbation of the glutamate-glutamine system in alcohol dependence and remission.

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 (1H-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 1H-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 1H-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.

Hippocampus volume and episodic memory in schizophrenia.

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.

Diffusion Tensor Imaging of White Matter Networks in Individuals with Current and Remitted Alcohol Use Disorders and Comorbid Conditions

Individuals with alcohol use disorders show white matter abnormality relative to normal samples, but 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 1 year (AUD-R; n = 9), and healthy control participants (HC; n = 15) matched to alcohol groups on age and smoking status underwent MRI. Diffusion tensor imaging (DTI) data were analyzed using tract-based spatial statistics (TBSS). Compared with 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.

Neurometabolite concentration and clinical features of chronic alcohol use: a proton magnetic resonance spectroscopy study.

Chronic, heavy alcohol consumption may affect the concentration of neurometabolites assessed with proton magnetic resonance spectroscopy ((1)H-MRS). We investigated the largest sample reported to date (N=213) with the primary goal of determining how specific clinical features impact neurometabolite concentrations in an anterior cingulate gray matter voxel. This community-dwelling sample included both treatment-seeking and non-treatment-seeking individuals. A healthy control group (N=66) was matched for age and education. In multivariate analyses predicting neurometabolite concentrations, the heavy drinking group had greater concentrations overall. An age by group interaction was noted, as group difference across neurometabolites increased with age. More years drinking, but not more drinks per drinking day (DPDD), predicted greater concentrations of choline-containing compounds (Cho), creatine-phosphocreatine (Cre), glutamate-glutamine (Glx), and N-acetyl-aspartate (NAA). The effects of other clinical variables (depression, cigarette smoking, marijuana use) were negligible. After controlling for DPDD and years drinking, treatment-seeking status had no impact on neurometabolites. In the very oldest portion of the sample (mean age=50), however, a negative relationship was seen between NAA and years drinking. These results suggest that the nature of neurometabolite abnormalities in chronic heavy drinkers may vary as a function of duration of abuse.

Associations of White Matter Microstructure with Clinical and Demographic Characteristics in Heavy Drinkers.

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.

Alcohol use predicts elevation in inflammatory marker soluble CD14 in men living with HIV

ABSTRACT Independently, HIV infection and heavy alcohol use increase microbial translocation (MT) of gut products into systemic circulation. MT and consequent immune response have been linked to chronic inflammation and a host of negative health outcomes in individuals living with HIV. However, previous research has not systematically investigated the immune correlates of heavy drinking specifically within the HIV-positive population. This pilot study investigated MT and immune activation as a function of alcohol use in 21 HIV-positive men who met NIAAA criteria for heavy drinking. Participants averaged 46.7 ± 8.5 (mean ± standard deviation) years of age, 12.2 ± 9.2 years since HIV diagnosis, 337 ± 158 CD4 nadir, and 643 ± 245 current CD4 count. All participants were virologically suppressed on antiretroviral therapy. Data on alcohol use and immune function were collected at baseline and three-month follow-up. Plasma concentrations of markers of MT and immune activation (lipopolysaccharide (LPS), soluble CD14 (sCD14), endotoxin core antibody immunoglobulin M (EndoCAb)) were measured using enzyme-linked immunosorbent assays. Generalized estimating equation models tested alcohol use variables as predictors of LPS, sCD14, and EndoCAb levels. Greater quantity and frequency of drinking significantly predicted higher sCD14 levels (p’s < .01). Conversely, longer duration of abstinence from alcohol significantly predicted lower sCD14 levels (p < .001). These results remained significant after controlling for age, HIV duration, smoking status, current CD4 count, CD4 nadir, and antiretroviral drug type. In addition, participants with ≥50% relative reduction in drinks per week showed a significant decrease (p < .05) in sCD14 from baseline to three-month follow-up. This pilot study provides preliminary evidence that heavy drinking may increase a key inflammatory marker in HIV-infected individuals with suppressed infection.

White matter integrity is associated with alcohol cue reactivity in heavy drinkers

Neuroimaging studies have shown that white matter damage accompanies excessive alcohol use, but the functional correlates of alcohol‐related white matter disruption remain unknown. This study applied tract‐based spatial statistics (TBSS) to diffusion tensor imaging (DTI) data from 332 heavy drinkers (mean age = 31.2 ± 9.4; 31% female) to obtain averaged fractional anisotropy (FA) values of 18 white matter tracts. Statistical analyses examined correlations of FA values with blood‐oxygenation‐level‐dependent (BOLD) response to an alcohol taste cue, measured with functional magnetic resonance imaging (fMRI). FA values of nine white matter tracts (anterior corona radiata, body of corpus callosum, cingulate gyrus, external capsule, fornix, inferior frontooccipital fasciculus, posterior corona radiata, retrolenticular limb of internal capsule, and superior longitudinal fasciculus) were significantly, negatively correlated with BOLD activation in medial frontal gyrus, parahippocampal gyrus, fusiform gyrus, cingulum, thalamus, caudate, putamen, insula, and cerebellum. The inverse relation between white matter integrity and functional activation during the alcohol taste cue provides support for the hypothesis that lower white matter integrity in frontoparietal and corticolimbic networks is a factor in loss of control over alcohol consumption.

Latent growth classes of alcohol-related blackouts over the first 2 years of college.

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 5 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 decrease; 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 decrease; 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 2 groups were distinguished by relatively moderate (moderate 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 precollege 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. (PsycINFO Database Record

Effects of smoking and alcohol use on neurocognitive functioning in heavy drinking, HIV-positive men who have sex with men.

ABSTRACT High rates of cognitive impairment persist in human immunodeficiency virus (HIV) infection, despite improved health outcomes and reduced mortality through widespread use of antiretroviral therapy (ART). Heavy alcohol use and cigarette smoking are potential contributors to neurocognitive impairment in people living with HIV (PLWH), yet few studies have examined their influence concurrently. Here we investigated the effects of self-reported alcohol use and smoking on learning, memory, processing speed, verbal fluency, and executive function in 124 HIV-positive men who have sex with men [age (mean ± SD) = 42.8 ± 10.4 years], engaged with medical care. All participants were heavy drinkers. Duration of HIV infection averaged 9.9 ± 7.6 years, and 92.7% were on a stable ART regimen. Participants completed a neuropsychological battery and assessment of past 30-day substance use. Average number of drinks per drinking day (DPDD) was 5.6 ± 3.5, and 33.1% of participants were daily smokers. Rates of neurocognitive impairment were the highest in learning (50.8%), executive function (41.9%), and memory (38.0%). Multiple regression models tested DPDD and smoking status as predictors of neurocognitive performance, controlling for age and premorbid intelligence. Smoking was significantly, negatively related to verbal learning (p = .046) and processing speed (p = .001). DPDD was a significant predictor of learning (p = .047) in a model that accounted for the interaction of DPDD and smoking status. As expected, premorbid intelligence significantly predicted all neurocognitive scores (ps < .01), and older age was associated with slower processing speed (ps < .01). In conclusion, smoking appears to be associated with neurocognitive functioning deficits in PLWH beyond the effects of heavy drinking, aging, and premorbid intelligence. Smoking cessation interventions have the potential to be an important target for improving functional outcomes in heavy drinking PLWH.