Identifying neurobiological phenotypes associated with alcohol use disorder severity

Abstract

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.

Figure 1

Main effect of blood oxygen level-dependent (BOLD) response to alcohol cues−litchi cues, cluster corrected at z>8, p<0.05, for visualization purposes. The comparison of alcohol cues to litchi cues showed significant differences in anterior and posterior cingulate cortex, dorsal striatum, insula, thalamus, and brainstem.

Figure 2

Correlation of blood oxygen level-dependent (BOLD) response with measures of alcohol abuse severity. Examination of the correlation between the alcohol–litchi contrast image and four measures of alcohol use severity/alcohol exposure suggests that craving responses for alcohol cues engage regions associated with habit learning and motor control in more experienced drinkers and those who experience more problems as a result of alcohol use (a–d). (e) Differences in the alcohol vs litchi contrast between treatment seekers and non-treatment seekers. Treatment seekers showed greater differences between the two conditions in the precuneus, SMA, compared with non-treatment seekers. All images are threshold at z=3.09, cluster corrected p<0.05, except where noted. (a) AUDIT—Alcohol Use Disorder Identification Test; (b) ADS—Alcohol Dependence Scale; (c) ICS-FC—Impaired Control Scale, Failed Control subscale; (d) years of regular drinking; and (e) treatment seeking vs non-treatment seeking.