Patterns of Gene Expression in the Frontal Cortex Discriminate Alcoholic from Nonalcoholic Individuals

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 31; no. 7; pp. 1574 - 1582
• Main Authors: JIANWEN LIU, LEWOHL, Joanne M, HARRIS, R. Adron, LYER, Vishwanath R, DODD, Peter R, RANDALL, Patrick K, MAYFIELD, R. Dayne
• Format: Journal Article
• Language: English
• Published: New York, NY Nature Publishing 01.07.2006; Nature Publishing Group
• Subjects: Addictive behaviors; Adult; Adult and adolescent clinical studies; Aged; Aged, 80 and over; Alcoholism; Alcoholism - metabolism; Alcoholism - pathology; Alcoholism - physiopathology; Alcoholism and acute alcohol poisoning; Biological and medical sciences; Case-Control Studies; Female; Frontal Lobe - physiology; Gene Expression - physiology; Gene Expression Profiling - methods; Gene Expression Regulation - physiology; Humans; Male; Medical sciences; Middle Aged; Oligonucleotide Array Sequence Analysis - methods; Postmortem Changes; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; RNA, Messenger - metabolism; Toxicology; Human; neural disease; Alcoholism; Central nervous system; DNA chip; Frontal cortex; Gene expression; Adhesion; In vitro; Encephalon; human brain; microarray; cell adhesion
• DOI: 10.1038/sj.npp.1300947
• ISSN: 0893-133X

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 (approximately 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.