Abstract

Background: Alcohol dependence (AD) is a chronic recurrent brain disease that causes a heavy disease burden worldwide, partly due to high relapse rates after detoxification. Verified biomarkers are not available for AD and its relapse, although the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) may play important roles in the mechanism of addiction. This study investigated AD- and relapse-associated functional connectivity (FC) of the NAc and mPFC with other brain regions during early abstinence.Methods: Sixty-eight hospitalized early-abstinence AD male patients and 68 age- and education-matched healthy controls (HCs) underwent resting-functional magnetic resonance imaging (r-fMRI). Using the NAc and mPFC as seeds, we calculated changes in FC between the seeds and other brain regions. Over a follow-up period of 6 months, patients were measured with the Alcohol Use Disorder Identification Test (AUDIT) scale to identify relapse outcomes (AUDIT ≥ 8).Results: Thirty-five (52.24%) of the AD patients relapsed during the follow-up period. AD displayed lower FC of the left fusiform, bilateral temporal superior and right postcentral regions with the NAc and lower FC of the right temporal inferior, bilateral temporal superior, and left cingulate anterior regions with the mPFC compared to controls. Among these FC changes, lower FC between the NAc and left fusiform, lower FC between the mPFC and left cingulate anterior cortex, and smoking status were independently associated with AD. Subjects in relapse exhibited lower FC of the right cingulate anterior cortex with NAc and of the left calcarine sulcus with mPFC compared to non-relapsed subjects; both of these reductions in FC independently predicted relapse. Additionally, FC between the mPFC and right frontal superior gyrus, as well as years of education, independently predicted relapse severity.Conclusion: This study found that values of FC between selected seeds (i.e., the NAc and the mPFC) and some other reward- and/or impulse-control-related brain regions were associated with AD and relapse; these FC values could be potential biomarkers of AD or for prediction of relapse. These findings may help to guide further research on the neurobiology of AD and other addictive disorders.

Highlights

  • Alcohol use disorder (AUD) is a major burden on public health

  • Partial correlation analyses yielded that respective functional connectivity (FC) values of the nucleus accumbens (NAc) with the left cingulate anterior cortex (r = −0.66, x = −6, y = 39, z = 0, PFWE < 0.001) (Figures 2A,C; Supplementary Table 5) and FC of medial prefrontal cortex (mPFC) with the right frontal superior gyrus (r = −0.67, x = 18, y = 3, z = 57, PFWE < 0.001) and with the left precentral (r = −0.64, x = −27, y = −15, z = 63, PFWE < 0.001) (Figures 2B,D,E; Supplementary Table 6) in the early-abstinence stage were negatively correlated with relapse severity based on the follow-up survey

  • According to the hypothesis that alcohol dependence (AD) is accompanied by an abnormal reward circuit and cognitive execution, which is mostly based on the findings of previous neuroimaging and neurobiological research, this study selected the NAc and mPFC as seeds to investigate resting-state FC associated with AD and its relapse after detoxification

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Summary

Introduction

Alcohol use disorder (AUD) is a major burden on public health. Alcohol may cause 5.3% of all deaths and 5.1% of disability-adjusted life years (DALYs) lost [3], and is the 3rd highest risk factor of disease and 7th highest risk factor when considering both deaths and DALYs together [4]. One of the main reasons for its large disease burden worldwide is that AD is a chronic encephalopathy with a high relapse rate [6]. Alcohol dependence (AD) is a chronic recurrent brain disease that causes a heavy disease burden worldwide, partly due to high relapse rates after detoxification. This study investigated AD- and relapse-associated functional connectivity (FC) of the NAc and mPFC with other brain regions during early abstinence

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