Disrupted ventromedial prefrontal function, alcohol craving, and subsequent relapse risk
Dongju Seo, Cheryl M Lacadie, Keri Tuit, Kwang-Ik Hong, R Todd Constable, Rajita Sinha, Dongju Seo, Cheryl M Lacadie, Keri Tuit, Kwang-Ik Hong, R Todd Constable, Rajita Sinha
Abstract
Importance: Alcohol dependence is a chronic relapsing illness; stress, alcohol-related cues, and neutral-relaxing states significantly influence craving and relapse risk. However, neural mechanisms underlying the association between these states and alcohol craving and relapse risk remain unclear.
Objectives: To identify neural correlates associated with alcohol craving and relapse outcomes in 45 treatment-engaged, 4- to 8-week abstinent alcohol-dependent (AD) patients, and to compare brain responses of 30 demographically matched AD patients and 30 healthy control subjects during stress, alcohol, and neutral-relaxing cues.
Design: Functional magnetic resonance imaging study while participants were engaging in brief individualized script-driven imagery trials of stress, alcohol cues, and neutral-relaxing scenarios, and a prospective clinical outcome design to assess alcohol relapse 90 days postdischarge from inpatient treatment in the AD group.
Settings: Inpatient treatment setting in a community mental health center and hospital-based research unit.
Patients: Forty-five recovering AD patients in inpatient treatment for examining relapse, and 30 healthy control subjects demographically matched to 30 AD patients (subgroup of the relapse sample) for group comparisons.
Intervention: Twelve-step recovery-based addiction treatment for the patient group.
Main outcomes and measures: Brain response, alcohol craving, and relapse outcome measures (time to relapse and relapse severity).
Results: Increased ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex (ACC) activation during neutral-relaxing trials was correlated with high alcohol cue-induced and stress-induced craving in early recovering AD patients (x = 6, y = 43, z = -6; P < .01, whole-brain corrected). This vmPFC/ACC hyperactivity significantly predicted subsequent alcohol relapse, with a hazards ratio greater than 8 for increased relapse risk. Additionally, vmPFC/ACC hyperactivation during neutral trials and reduced activity during stress trials were each predictive of greater days of alcohol used after relapse (P < .01, whole-brain corrected). In contrast, matched control subjects showed the reverse pattern of vmPFC/ACC responses to stress, alcohol cues, and relaxed trials (F = 6.42; P < .01, whole-brain corrected).
Conclusions and relevance: Findings indicate that disrupted vmPFC/ACC function plays a role in jeopardizing recovery from alcoholism and may serve as a neural marker to identify those at risk for alcohol relapse.
Conflict of interest statement
Conflict of Interest Disclosures: Dr Sinha is on the scientific advisory board for Embera Neurotherapeutics.
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