Abstract

Dissimilar gene expression patterns in depressive subjects with a history of alcohol use

Medina A, Burke S, Bunney WE, Myers RM, Schatzberg AF, Barchas JD, Akil H, Jones EG, Watson SJ
Society for Neuroscience. 2011.

Alcohol consumption is a common behavior among Major Depression Disorder (MDD) patients. According to the National Epidemiologic Survey on Alcohol and Related conditions, about 11% of MDD patients also suffer from alcohol dependence comorbidity and 20% of alcohol dependent individuals experience comorbid depression. In this study we used microarray technology to compare the gene expression patterns of controls, MDD subjects with a history of heavy drinking (MDDa+) and MDD non-drinkers (MDDa-). Materials and methods: Fresh frozen hippocampus samples from 9 healthy, alcohol- free controls, 8 MDD subjects with history of heavy alcohol consumption at the time of death (MDDa+) and 6 MDD with no history of drinking (MDDa-) were dissected and sectioned at 10 um on a cryostat. The sections were anatomically aligned using a combination of in situ hybridization and classic histological techniques to select homologous levels of the hippocampus and laser capture microdissection was used to collect the tissue. Samples were processed using Illumina Human HT-12 v4.0 arrays (illumina Inc, Hayward, CA). Control versus disease expression differences were assessed using Student’s t-test. The resulting p values were then loaded in to Ingenuity Pathway Analysis (IPA, Ingenuity Systems, Redwood City, CA) to identify compromised cellular pathways for each disease group.

Results: IPA analysis of the MDDa+ group rendered 543 network eligible molecules altered compared to control, whereas for the MDDa- group 461 molecules where different from control. 246 altered molecules were common to both disease groups. Conclusion: Our study suggests that gene expression differs between MDDa+ and MDDa- subjects and both groups differ from controls. Although some altered genes are common to both MDD groups, IPA results suggest functional differences between these two groups.