Neural responses to reward, threat, and emotion regulation and transition to hazardous alcohol use.

AIMS: Reward processing and regulation of emotions are thought to impact the development of addictive behaviors. In this study, we aimed to determine whether neural responses during reward anticipation, threat appraisal, emotion reactivity, and cognitive reappraisal predicted the transition from low-level to hazardous alcohol use over a 12-month period. METHODS: Seventy-eight individuals aged 18-22 with low-level alcohol use [i.e. Alcohol Use Disorder Identification Test (AUDIT) score <7] at baseline were enrolled. They completed reward-based and emotion regulation tasks during magnetic resonance imaging to examine reward anticipation, emotional reactivity, cognitive reappraisal, and threat anticipation (in the nucleus accumbens, amygdala, superior frontal gyrus, and insula, respectively). Participants completed self-report measures at 3-, 6-, 9-, and 12-month follow-up time points to determine if they transitioned to hazardous use (as defined by AUDIT scores ≥8). RESULTS: Of the 57 participants who completed follow-up, 14 (24.6%) transitioned to hazardous alcohol use. Higher baseline AUDIT scores were associated with greater odds of transitioning to hazardous use (odds ratio = 1.73, 95% confidence interval 1.13-2.66, P = .005). Brain activation to reward, threat, and emotion regulation was not associated with alcohol use. Of the neural variables, the amygdala response to negative imagery was numerically larger in young adults who transitioned to hazardous use (g = 0.31), but this effect was not significant. CONCLUSIONS: Baseline drinking levels were significantly associated with the transition to hazardous alcohol use. Studies with larger samples and longer follow-up should test whether the amygdala response to negative emotional imagery can be used to indicate a future transition to hazardous alcohol use.

Neural response to threat and reward among young adults at risk for alcohol use disorder.

Alcohol use disorder (AUD) is heritable. Thus, young adults with positive family histories represent an at-risk group relative to those without a family history, and if studied at a time when both groups have similar levels of alcohol use, it provides an opportunity to identify neural processing patterns associated with risk for AUD. Previous studies have shown that diminished response to potential reward is associated with genetic risk for AUD, but it is unclear how threat may modulate this response. We used a modified Monetary Incentive Delay task during fMRI to examine neural correlates of the interaction between threat and reward anticipation in a sample of young adults with (n = 31) and without (n = 44) family histories of harmful alcohol use. We found an interaction (p = 0.048) between cue and group in the right nucleus accumbens where the family history positive group showed less differentiation to the anticipation of gaining $5 and losing $5 relative to gaining $0. The family history-positive group also reported less excitement for trials to gain $5 relative to gaining $0 (p < 0.001). Family history-positive individuals showed less activation in the left insula during both safe and threat blocks compared to family history-negative individuals (p = 0.005), but the groups did not differ as a function of threat (p > 0.70). Young adults with, relative to without, enriched risk for AUD may have diminished reward processing via both neural and behavioural markers to potential rewarding and negative consequences. Neural response to threat may not be a contributing factor to risk at this stage.

NEURAL RESPONSE TO THREAT AND REWARD AMONG YOUNG ADULTS AT RISK FOR ALCOHOL USE DISORDER.

Alcohol use disorder is 50% heritable; those with positive family histories represent an at-risk group within which we can test anticipation of threat and reward prior to development of harmful alcohol use. We examined neural correlates of the interaction between family history, threat anticipation (unpredictable threat), and monetary reward anticipation, in a sample of healthy young adults with (n=31) and without (n=44) family histories of harmful alcohol use. We used a modified Monetary Incentive Delay task with sustained threat of hearing a scream during fMRI. We examined the interaction between family history group, anticipation of threat, and anticipation of reward in the insula, nucleus accumbens, and medial prefrontal cortex. Family history positive individuals showed less activation in the left insula during both safe and threat blocks compared to family history negative individuals (p=0.005), but the groups did not differ as a function of unpredictable threat (p>0.70). We found an interaction (p=0.048) between cue and group in the right nucleus accumbens where the family history positive group showed less differentiation to the anticipation of gaining $5 and losing $5 relative to gaining $0. The family history positive group also reported less excitement for trials to gain $5 relative to gaining $0 (p<0.001). Prior to chronic heavy alcohol use, individuals with, relative to without, enriched risk may have diminished reward processing via both neural and behavioral markers to potential rewarding and negative consequences. Neural response to unpredictable threat may not be a contributing factor to risk at this stage.