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Transcription profiling reveals mitochondrial, ubiquitin and signaling systems abnormalities in postmortem brains from subjects with a history of alcohol abuse or dependence
Author(s) -
Sokolov Boris P.,
Jiang Lixin,
Trivedi Niraj S.,
Aston Christopher
Publication year - 2003
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10631
Subject(s) - alcohol dependence , alcohol abuse , psychiatry , medicine , comorbidity , alcohol , psychology , clinical psychology , biology , biochemistry
Alcohol abuse is a common human disorder with high rate of comorbidity with other psychiatric disorders. To identify candidate mechanisms for alcohol abuse, the expression of 12,626 genes was measured in postmortem temporal cortex from 11 subjects with a history of alcohol abuse or dependence, with or without other psychiatric diagnoses and compared pairwise with the expression in 11 nonalcoholic subjects matched for the other psychiatric diagnoses and demographics. Genes were defined to have altered expression in alcohol abuse if: 1) the gene showed decreased expression in at least 10 of 11 subjects with alcohol abuse, or showed increased expression in at least 10 of 11 subjects with this diagnosis compared to matched non‐abusers ( P < 0.007, χ 2 test); or 2) the difference in the mean abuser/non‐abuser ratio for the gene from value of 1.0 was significant at P < 0.05 (one sample t ‐test). In subjects with a history of alcohol abuse or dependence, 163 genes were changed significantly. The most abundant and consistent changes were in gene families encoding mitochondrial proteins, the ubiquitin system, and signal transduction. These alterations indicate disturbances in energy metabolism and multiple signaling mechanisms in the temporal cortex of subjects with a history of alcohol abuse or dependence. We hypothesize that these mechanisms may be related to alcohol abuse traits or long‐term effects of alcohol. © 2003 Wiley‐Liss, Inc.