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Relationship Between Liver Function and Brain Shrinkage in Patients with Alcohol Dependence

Authors

  • Chun-Hsin Chen,

    1. From the Laboratory of Clinical and Translational Studies (C-HC, JW, RM, RR, MH, DWH), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Department of Psychiatry (CHC), Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan; and Department of Psychiatry (CHC), School of Medicine, Taipei Medical University, Taipei, Taiwan.
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  • Jonathan Walker,

    1. From the Laboratory of Clinical and Translational Studies (C-HC, JW, RM, RR, MH, DWH), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Department of Psychiatry (CHC), Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan; and Department of Psychiatry (CHC), School of Medicine, Taipei Medical University, Taipei, Taiwan.
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  • Reza Momenan,

    1. From the Laboratory of Clinical and Translational Studies (C-HC, JW, RM, RR, MH, DWH), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Department of Psychiatry (CHC), Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan; and Department of Psychiatry (CHC), School of Medicine, Taipei Medical University, Taipei, Taiwan.
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  • Robert Rawlings,

    1. From the Laboratory of Clinical and Translational Studies (C-HC, JW, RM, RR, MH, DWH), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Department of Psychiatry (CHC), Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan; and Department of Psychiatry (CHC), School of Medicine, Taipei Medical University, Taipei, Taiwan.
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  • Markus Heilig,

    1. From the Laboratory of Clinical and Translational Studies (C-HC, JW, RM, RR, MH, DWH), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Department of Psychiatry (CHC), Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan; and Department of Psychiatry (CHC), School of Medicine, Taipei Medical University, Taipei, Taiwan.
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  • Daniel W. Hommer

    1. From the Laboratory of Clinical and Translational Studies (C-HC, JW, RM, RR, MH, DWH), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Department of Psychiatry (CHC), Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan; and Department of Psychiatry (CHC), School of Medicine, Taipei Medical University, Taipei, Taiwan.
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Reprint requests: Daniel W. Hommer, MD, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 10 Center Drive, Building 10-CRC – Hatfield Clinical Research Center, Room 1-5330, Bethesda, MD 20892; Tel.: 301-402-6094; Fax: 301-402-0445; E-mail: danh@mail.nih.gov

Abstract

Background:  Oxidative stress has been proposed as one of the mechanisms of alcohol-induced brain shrinkage and alcohol-induced hepatotoxicity. The aim of this study was to assess the correlations between liver function and brain volume (BV) measurements in patients with alcohol dependence.

Methods:  We recruited 124 patients with alcohol dependence and 111 healthy control subjects from National Institute of Health, National Institute on Alcohol Abuse and Alcoholism inpatient alcohol treatment program. Gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), as well as hematocrit (Hct) and albumin were assayed shortly after admission. Magnetic resonance imaging examination was conducted in both groups (after 3-week abstinence in the patient group). We used stepwise linear regression analyses to determine the variables most strongly correlated with brain shrinkage.

Results:  Patients with alcohol dependence had lower BV, and greater brain shrinkage as measured by gray matter ratio (GMR), white matter ratio (WMR), brain ratio (BR), and higher cerebrospinal fluid ratio ratio (CSFR) compared with their healthy counterparts. Age and sex were significantly correlated with some BV measurements in both patient and control groups. Body mass index (BMI) was significantly correlated with CSFR, BR, GMR, and WMR; Hct with CSFR and BR; serum GGT level with BV, CSFR, BR, GMR, and WMF in the patient group. No biological variables were correlated with BV indices in the control group. In gender-stratified analysis, age was significantly correlated with brain shrinkage in male patients but not in female patients. Serum GGT level in male and female patients, Hct in male patients, and AST levels in female patients were significantly correlated with brain shrinkage.

Conclusions:  Our results showed that the higher levels of liver function indices, especially GGT, correlated with BV shrinkage as measured using CSFR, BR, GMR, and WMR in patients with alcohol dependence but not in controls. Serum GGT level outweighed aging effect on brain shrinkage in female patients.

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