Divergent responses of the amygdala and ventral striatum predict stress-related problem drinking in young adults: possible differential markers of affective and impulsive pathways of risk for alcohol use disorder

Abstract

Prior work suggests there may be two distinct pathways of alcohol use disorder (AUD) risk: one associated with positive emotion enhancement and behavioral impulsivity, and one associated with negative emotion relief and coping. We sought to map these two pathways onto individual differences in neural reward and threat processing assessed using BOLD fMRI in a sample of 759 undergraduate students (426 women, mean age 19.65±1.24) participating in the Duke Neurogenetics Study. We demonstrate that problem drinking is highest in the context of stress and in those with one of two distinct neural phenotypes: 1) a combination of relatively low reward-related activity of the ventral striatum (VS) and high threat-related reactivity of the amygdala; or 2) a combination of relatively high VS activity and low amygdala reactivity. In addition, we demonstrate that the relationship between stress and problem alcohol use is mediated by impulsivity, as reflected in monetary delay discounting rates, for those with high VS-low amygdala reactivity, and by anxious/depressive symptomatology for those with the opposite neural risk phenotype. Across both neural phenotypes, we found that greater divergence between VS and amygdala reactivity predicted greater risk for problem drinking. Finally, for those individuals with the low VS-high amygdala risk phenotype we found that stress not only predicted the presence of a DSM-IV diagnosed AUD at the time of neuroimaging, but also subsequent problem drinking reported three months following study completion. These results offer new insight into the neural basis of AUD risk and suggest novel biological targets for early individualized treatment or prevention.

Evidence for GABA‐A receptor dysregulation in gambling disorder: correlation with impulsivity

“…Based upon our previous findings in alcohol and opiate dependence for the [ 11 C]Ro15‐4513 PET analysis, we selected right hippocampus and NAc as a priori ROIs, and we chose two additional a priori ROIs based upon their established role in impulse control: OFC and amygdala (Goldstein and Volkow 2002; Jentsch and Taylor 1999; Ko et al 2015; Nikolova et al 2016). As previous work (Clark et al 2012; Michalczuk et al 2011) has shown that NU, as a mood‐related subgroup of impulsivity, is most strongly associated with GD, we chose to test for correlations between UPPS‐P NU and a priori selected brain regions.…”

Neuroimaging tests for clinical psychiatry: Are we there yet?

“…In 759 emerging adults (average age 19.6 ± 1.2 years), 2 distinct markers of stress-related problem drinking were identified. 15 One group exhibited elevated threat-induced activations of the amygdala coupled with reduced reward-related activations of the ventral striatum. The second group exhibited the converse pattern: elevated reward-related activations in the ventral striatum and diminished threat-induced activations in the amygdala.…”

Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery

“…1 Threat-related reactivity of the amygdala, for example, is strongly associated with negatively reinforced problem drinking. 10 Connectivity between the amygdala and the hippocampus is associated with maladaptive emotional processing, 11 and alterations in hippocampal network activation and connectivity have been shown to predict relapse. 12 The prefrontal cortex has extensive connections with subcortical structures that regulate emotional processing, including the amygdala.…”

“…We sought to determine the effects of naltrexone at standard dose (50 mg) during negative emotional processing between groups dependent on alcohol alone, dependent on alcohol and drugs (both in abstinence) and healthy control volunteers. On the basis of previous research showing altered activation in limbic and cortical networks during negative emotional processing in substance-dependent individuals, 1,[10][11][12][13][14][15] including the processing of evocative 16 and negative emotional images, 38,39 we hypothesized that the dependent groups would show increased activation in the amygdala, the mPFC and the hippocampus in response to aversive images. In light of preclinical evidence, 29 we further hypothesized that these effects would be modulated by naltrexone depending on the degree of childhood adversity experienced.…”