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.
Recent research has suggested that marijuana use is associated with volumetric and shape differences in subcortical structures, including the nucleus accumbens and amygdala, in a dose-dependent ...fashion. Replication of such results in well controlled studies is essential to clarify the effects of marijuana. To that end, this retrospective study examined brain morphology in a sample of adult daily marijuana users (n = 29) versus nonusers (n = 29) and a sample of adolescent daily users (n = 50) versus nonusers (n = 50). Groups were matched on a critical confounding variable, alcohol use, to a far greater degree than in previously published studies. We acquired high-resolution MRI scans, and investigated group differences in gray matter using voxel-based morphometry, surface-based morphometry, and shape analysis in structures suggested to be associated with marijuana use, as follows: the nucleus accumbens, amygdala, hippocampus, and cerebellum. No statistically significant differences were found between daily users and nonusers on volume or shape in the regions of interest. Effect sizes suggest that the failure to find differences was not due to a lack of statistical power, but rather was due to the lack of even a modest effect. In sum, the results indicate that, when carefully controlling for alcohol use, gender, age, and other variables, there is no association between marijuana use and standard volumetric or shape measurements of subcortical structures.
Although numerous studies provide general support for the importance of genetic factors in the risk for alcohol use disorders (AUDs), candidate gene and genome-wide studies have yet to identify a set ...of genetic variations that explain a significant portion of the variance in AUDs. One reason is that alcohol-related phenotypes used in genetic studies are typically based on highly heterogeneous diagnostic categories. Therefore, identifying neurobiological phenotypes related to neuroadaptations that drive the development of AUDs is critical for the future success of genetic and epigenetic studies. One such neurobiological phenotype is the degree to which exposure to alcohol taste cues recruits the basal ganglia, prefrontal cortex, and motor areas, all of which have been shown to have a critical role in addictive behaviors in animal studies. To that end, this study was designed to examine whether cue-elicited responses of these structures are associated with AUD severity in a large sample (n=326) using voxelwise and functional connectivity measures. Results suggested that alcohol cues significantly activated dorsal striatum, insula/orbitofrontal cortex, anterior cingulate cortex, and ventral tegmental area. AUD severity was moderately correlated with regions involved in incentive salience such as the nucleus accumbens and amygdala, and stronger relationships with precuneus, insula, and dorsal striatum. The findings indicate that AUDs are related to neuroadaptations in these regions and that these measures may represent important neurobiological phenotypes for subsequent genetic studies.
Background and Aims
Chronic alcohol use is associated with lower gray matter volume, and we reported recently that alcohol use showed negative associations with widespread gray matter (GM) volume ...even among young adults. The current study aimed to test the strength of association between (1) alcohol use and GM volume; (2) alcohol use and white matter (WM) integrity; (3) cannabis use and GM volume; and (4) cannabis use and WM integrity among adults and adolescents.
Design and Setting
General linear models within large pooled cross‐sectional samples of adolescents and adults who had participated in studies collecting substance use and neuroimaging data in the southwestern United States.
Participants
The current analysis included adults aged 18–55 years (n = 853) and adolescents aged 14–18 years (n = 439) with a range of alcohol and cannabis use.
Measurements
The dependent variable was GM volume or WM integrity, with key predictors of alcohol use Alcohol Use Disorders Identification Test (AUDIT) score and cannabis use (past 30‐day use).
Findings
Alcohol use showed large clusters of negative associations (ηp2 = 0.028–0.145, P < 0.001) with GM volume among adults and to a lesser extent (one cluster; ηp2 = 0.070, P < 0.05) among adolescents. Large clusters showed significant associations (ηp2 = 0.050–0.124, P < 0.001) of higher alcohol use with poorer WM integrity, whereas adolescents showed no significant associations between alcohol use and WM. No associations were observed between structural measures and past 30‐day cannabis use in adults or adolescents.
Conclusions
Alcohol use severity is associated with widespread lower gray matter volume and white matter integrity in adults, and with lower gray matter volume in adolescents.
Background
Altered functional connectivity in critical networks has been associated with chronic alcohol abuse. In turn, changes in connectivity in executive control networks (ECNs) may undermine the ...ability to control alcohol consumption. It was hypothesized that network connectivity would be reduced in individuals with problematic alcohol use (ALC) compared with controls and that diminished network connectivity would be associated with greater failure to control drinking.
Methods
Resting‐state functional magnetic resonance imaging was analyzed to identify 14 previously identified intrinsic connectivity networks (ICNs) using a priori regions of interest in cases ranging from binge drinkers to those with severe alcohol use disorder, as well as control subjects. Analyses tested for differences in network connectivity strength between 255 ALC cases and 87 age‐ and gender‐matched controls. Further, structural equation analysis, using 383 ALC cases, tested whether functional connectivity strength mediated the relationship between years of regular drinking and alcohol problems.
Results
The age‐ and gender‐matched analysis showed that ALC had significantly lower network connectivity strength than controls in the left executive control (LECN), basal ganglia, and primary visual networks. For all ALC, LECN connectivity strength is negatively correlated with failed control and alcohol disorder severity. Edges connecting parietal regions with dorsolateral prefrontal, middle frontal, and temporal regions within the LECN drove these relationships. A positive association between years of drinking and severity of alcohol problems was mediated by reduced ECN connectivity.
Conclusions
This study reports relationships between network strength and problematic alcohol use, suggesting that chronic drinking negatively impacts brain connectivity, specifically in the LECN. Altered functional connectivity, related to chronic alcohol abuse, may contribute to the etiology of alcohol dependence and relapse.
Background: Current work in motivational interviewing (MI) has supported the role of in‐session client and therapist language in predicting postintervention substance use outcomes. In particular, a ...relationship has been found between specific therapist language (e.g., MI‐consistent behaviors), specific types of client speech (e.g., change talk; CT and counterchange talk; CCT), and subsequent drinking outcomes. One hypothesis to explain this phenomenon is that CT is an indication of a neurocognitive shift that happens during the course of a psychosocial intervention. And, it is possible that this shift is responsible for catalyzing and maintaining changes in drinking behaviors following MI interventions. To investigate this question, the effect of CT on blood oxygen level–dependent (BOLD) response during the presentation of alcohol cues was evaluated using functional magnetic resonance imaging.
Methods: To examine changes in neural response to alcohol cues following client language, 10 adults with alcohol dependence (50% men; 40% Caucasian; 40% Hispanic; M age = 42.6; M years of education = 13.3) were presented with CT and CCT derived from their prescan MI session during the presentation of alcohol cues.
Results: Following CCT, there was significant neural response to alcohol cues in several key reward areas (cluster‐corrected p < 0.05, z > 2.3; orbitofrontal cortex, nucleus accumbens, anterior insula, posterior insula, caudate, and putamen). On the contrary, there were no areas of significant reward activation following CT.
Conclusions: These results indicate that CT may be effectively inhibiting activation in brain regions that respond to the salience of alcohol cues. These findings provide preliminary biological support of the psychosocial literature findings, highlighting the critical importance of change talk during psychosocial interventions.
Chronic exposure to alcohol and other drugs of abuse has been associated with deleterious consequences, including functional connectivity deficits within neural networks associated with executive ...control. Altered functional connectivity within the executive control network (ECN) might underlie the progressive inability to control consumption of alcohol and other drugs as substance use disorders progress. Genetic and epigenetic factors have been associated with substance use disorders (SUDs). For example, dopamine receptor 2 (DRD2) functioning has been associated with alcohol use disorder (AUD) and related phenotypes, including correlates of executive functioning. The present study aims to explore the relationship between a continuous measure of alcohol‐related problems, epigenetic markers (methylation) within the DRD2 gene, and functional connectivity within the ECN among a sample of polysubstance users. A community sample of 658 subjects, whose consumption of alcohol, nicotine, and cannabis span across a spectrum of quantity and frequency of use, were obtained across previous studies in polysubstance using populations. Resting state functional magnetic resonance imaging was analyzed to identify intrinsic connectivity networks using a priori regions of interest. Methylation measurement of functionally relevant sites within the DRD2 gene was achieved via pyrosequencing. Regression‐based models, including mediation and moderation models, tested the association between DRD2 methylation, functional connectivity within intrinsic neural networks (including the ECN), and severity of alcohol problems. Results suggest that average DRD2 methylation was negatively associated with right ECN (RECN) and left ECN (LECN) connectivity, but not associated with other networks tested, and DRD2 methylation was significantly associated with alcohol problems severity. Mediation models were not supported, although moderation models suggested that connectivity between edges within the RECN moderated the relationship between DRD2 methylation and AUD severity. Results support a theoretical model in which epigenetic factors are associated with neurobiological correlates of alcohol consumption among a sample of polysubstance users.
The figure depicts a working model of the role of epigenetics in neural network changes in response to chronic alcohol consumption. The current investigation provides cross‐sectional evidence that severity of alcohol problems is associated with DRD2 methylation in the periphery, which is in turn associated with decreased executive control network connectivity among a sample of polysubstance users.
PDF
