1. ¹Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX, USA
2. ²Genomics Research Centre, School of Health Sciences, Griffith University, Qld, Australia
3. ³Section of Molecular Genetics and Microbiology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, USA
4. ⁴Department of Biochemistry, University of Queensland, Qld, Australia
5. ⁵Charleston Alcohol Research Center, Medical University of South Carolina, Charleston, SC, USA

Correspondence: Dr RD Mayfield, Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, 2500 Speedway, MBB 1.124, Austin, TX 78712, USA. Tel: +1 512 232 2512; Fax: +1 512 232 2525; E-mail: dayne.mayfield@mail.utexas.edu

Received 8 March 2005; Revised 10 August 2005; Accepted 16 September 2005; Published online 2 November 2005.

Abstract

Alcohol dependence is characterized by tolerance, physical dependence, and craving. The neuroadaptations underlying these effects of chronic alcohol abuse are likely due to altered gene expression. Previous gene expression studies using human post-mortem brain demonstrated that several gene families were altered by alcohol abuse. However, most of these changes in gene expression were small. It is not clear if gene expression profiles have sufficient power to discriminate control from alcoholic individuals and how consistent gene expression changes are when a relatively large sample size is examined. In the present study, microarray analysis (47 000 elements) was performed on the superior frontal cortex of 27 individual human cases (14 well characterized alcoholics and 13 matched controls). A partial least squares statistical procedure was applied to identify genes with altered expression levels in alcoholics. We found that genes involved in myelination, ubiquitination, apoptosis, cell adhesion, neurogenesis, and neural disease showed altered expression levels. Importantly, genes involved in neurodegenerative diseases such as Alzheimer's disease were significantly altered suggesting a link between alcoholism and other neurodegenerative conditions. A total of 27 genes identified in this study were previously shown to be changed by alcohol abuse in previous studies of human post-mortem brain. These results revealed a consistent re-programming of gene expression in alcohol abusers that reliably discriminates alcoholic from non-alcoholic individuals.