Loss of control of alcohol use and severity of alcohol dependence in non-treatment-seeking heavy drinkers are related to lower glutamate in frontal white matter.

BACKGROUND: The development and maintenance of alcohol use disorders (AUD) have been hypothesized to be associated with an imbalance of glutamate (GLU) homeostasis. White matter (WM) loss, especially in anterior brain regions, has been reported in alcohol dependence, which may involve disturbances in both myelin and axonal integrity. Frontal lobe dysfunction plays an important role in addiction, because it is suggested to be associated with the loss of control over substance use. This study investigated magnetic resonance spectroscopy (MRS)-detectable Glu levels in frontal WM of non-treatment-seeking heavy drinkers and its associations with AUD symptoms. METHODS: Single-voxel MR spectra optimized for Glu assessment (TE 80 ms) were acquired at 3T from a frontal WM voxel in a group of heavy drinking, non-treatment-seeking subjects in comparison with a group of subjects with only light alcohol consumption. RESULTS: The results corroborate previous findings of increased total choline in heavy drinking subjects. A negative association of Glu levels with severity of alcohol dependence and especially loss of control over time and amount of alcohol intake was observed. CONCLUSIONS: In contrast to the rather unspecific rise in choline-containing compounds, low Glu in frontal WM may be specific for the shift from nondependent heavy drinking to dependence and does not reflect a simple effect of the amount of alcohol consumption alone.

Initial, habitual and compulsive alcohol use is characterized by a shift of cue processing from ventral to dorsal striatum.

AIMS: During the development of drug addiction, initial hedonic effects decrease when substance use becomes habitual and ultimately compulsive. Animal research suggests that these changes are represented by a transition from prefrontal cortical control to subcortical striatal control and within the striatum from ventral to dorsal domains of the striatum, but only limited evidence exists in humans. In this study we address this hypothesis in the context of alcohol dependence. DESIGN, SETTING AND PARTICIPANTS: Non-abstinent heavy social drinkers (n = 21, 5.0 ± 1.5 drinks/day, 13 of them were alcohol-dependent according to DSM-IV) and light social drinkers (n = 10, 0.4 ± 0.4 drinks/day) were examined. MEASUREMENTS: We used a cue-reactivity functional magnetic resonance imaging (fMRI) design during which pictures of alcoholic beverages and neutral control stimuli were presented. FINDINGS: In the dorsal striatum heavy drinkers showed significant higher activations compared to light drinkers, whereas light social drinkers showed higher cue-induced fMRI activations in the ventral striatum and in prefrontal areas compared to heavy social drinkers [region of interest analyses, P < 0.05 false discovery rate (FDR)-corrected]. Correspondingly, ventral striatal activation in heavy drinkers correlated negatively with obsessive-compulsive craving, and furthermore we found a positive association between cue-induced activation in the dorsal striatum and obsessive-compulsive craving in all participants. CONCLUSIONS: In line with our hypothesis we found higher cue-induced activation of the ventral striatum in social compared to heavy drinkers, and higher dorsal striatal activation in heavy drinkers. Increased prefrontal activation may indicate that social drinkers activate cortical control when viewing alcohol cues, which may prevent the development of heavy drinking or alcohol dependence. Our results suggest differentiating treatment research depending on whether alcohol use is hedonic or compulsive.

Increased activation of the ACC during a spatial working memory task in alcohol-dependence versus heavy social drinking.

BACKGROUND: Activation of the anterior cingulate cortex (ACC) in a spatial working memory task has been associated with risk factors for alcohol use disorders such as low alcohol effects and positive alcohol expectations in adolescents. To transfer these results into adults, we used the same task in adults. METHODS: During functional magnetic resonance imaging, 12 light social, 7 heavy social, and 11 non-abstinent-dependent alcohol drinkers performed a spatial working memory task and completed measures of automatic alcohol-related thoughts and behavior (Obsessive-Compulsive Drinking Scale-OCDS), alcohol use of the last 90 days, and general intelligence. RESULTS: Behavioral performance in the spatial working memory task was not significantly different in all 3 groups. Controlling for differences in general intelligence alcohol-dependent participants showed a higher task-related activation of the dorsal ACC (dACC) in comparison with light and heavy social drinkers. Measures of the OCDS were positively correlated with the activation in the left hippocampus and right thalamus in all participants. CONCLUSIONS: Our results support the findings of increased dACC activation during a spatial working memory task as a risk factor for alcohol dependence. Increased task-related activation in the dACC was only observed in alcohol-dependent participants and not in heavy social drinkers with comparable alcohol consumption. Furthermore, the absence of behavioral performance differences between groups as well as an association between dACC activation and working memory performance indicates subtle working memory deficits. Low capacity of working memory has been linked to more automatic and less self-regulated behavior in studies on natural reward processing. Therefore, additional neural activation during performance of the non-alcohol-related working memory task in participants with higher OCDS values in the left hippocampus and the right thalamus may be a consequence of decreased neural capacity because of distracting alcohol-related thoughts.