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.
- Authors
- Nikolova, Y S; Knodt, A R; Radtke, S R; Hariri, A R
- Year
- 2016
- Journal
- Molecular psychiatry
- PMID
- 26122584
- DOI
- 10.1038/mp.2015.85
- PMCID
- PMC4696925
Prior work suggests that there may be two distinct pathways of alcohol use disorder (AUD) risk: one associated with positive emotion enhancement and behavioral impulsivity, and another 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 blood-oxygen-level-dependent functional magnetic resonance imaging in a sample of 759 undergraduate students (426 women, mean age 19.65±1.24 years) 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 AUD diagnosis at the time of neuroimaging but also subsequent problem drinking reported 3 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.
(a) Statistical parametric map illustrating mean bilateral threat-related amygdala reactivity (left: x=−22, y=−6, z=−18, t=38.64, p<0.000001, kE=167; right: x=28, y=−4, z=−20, t=42.97, p<0.000001, kE=198). (b) Statistical parametric map illustrating mean bilateral reward-related VS reactivity (left: x=−12, y=8, z=−8, t=13.12, p<0.000001, kE=303; right: x=12, y=10, z=−8, t=12.63, p<0.000001, kE=290). Activation clusters in (a) and (b) are overlaid onto canonical structural brain images in the coronal plane.
Amygdala and VS reactivity jointly moderated the relation between recent life stress and problem drinking. Slopes represent beta coefficient estimates reflecting the strength of the relation between LESS and AUDIT scores (a–b) or AUD diagnosis (c–d) at varying levels of amygdala and VS activity. High levels of stress were associated with larger increases in AUDIT scores for participants with a combination of (a) low VS (-1SD) and high amygdala (+1SD) reactivity or (b) high VS and low amygdala reactivity. High levels of stress were also associated with larger increases in the likelihood of having a concurrent AUD diagnosis for those with low VS and high amygdala reactivity (c), but not with those with high VS and low amygdala reactivity (d), for whom this relationship was only observed at 2.5 SD >mean (data not shown). Simple slopes are adjusted for gender, age, race/ethnicity and CTQ.
Conceptual depiction of the path analytic models tested to evaluate anxious/depressive symptomatology and delay discounting as mediators of the relation between stress and problem drinking at different levels of amygdala and VS reactivity.
Results from path analytic moderated mediation models using (a) anxious/depressive symptoms and (b) delay discounting as mediators between LESS and AUDIT at varying levels of VS and amygdala reactivity. Raw regression coefficients are presented for each path, along with standard errors in parentheses. Covariates in both models include gender, age, race/ethnicity (dummy coded) and CTQ. MASQ AD was additionally controlled for in (a). For the sake of brevity, individual covariates and their associated paths are not depicted. Variance in the mediators and AUDIT scores unaccounted for by the model are denoted as e1 and e2, respectively.**p<0.001*p<0.05#p<0.1
Amygdala and VS reactivity jointly moderated the relation between recent life stress and problem drinking three months following initial study completion. Slopes represent beta coefficient estimates reflecting the strength of the relation between LESS and AUDIT scores, measured at the three month follow-up assessment, as a function of varying levels of amygdala and VS activity assessed at baseline. High levels of stress were associated with larger increases in AUDIT scores for participants with a combination of low VS (-1SD) and high amygdala (+1SD) reactivity (a), but not for those with a combination of high VS and low amygdala reactivity (b). Simple slopes are adjusted for gender, age, race/ethnicity and CTQ.
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