Undergraduate Honors Theses

Thesis Defended

Spring 2016

Document Type

Thesis

Type of Thesis

Departmental Honors

Department

Psychology & Neuroscience

First Advisor

Dr. Kent Hutchison

Second Advisor

Dr. Angela Bryan

Third Advisor

Dr. Alison Vigers

Abstract

Abstract

Background: Alcohol use disorder (AUD) is a significant health problem in the U.S. Specifically, AUD is associated with memory problems and other cognitive defects. DNA methylation of CpG sites and other epigenetic factors have been found to play an important role in the development of Alcohol Use Disorders (AUD). Because of this, it was hypothesized that individuals with AUD would show differential methylation in neurotrophic factors, specifically, the BDNF gene, as compared to controls.

Methods: Precuneus brain tissue from 49 Alcohol Use Disorder cases and 47 controls were obtained from the New South Wales and Victorian Tissue Resource Centre. DNA from each sample was extracted, and methylation levels were analyzed using Infinium HumanMethylation450 BeadChip. 450,000 CpG sites were interrogated between AUD cases and controls; however, only 97 CpG sites in the Brain-derived neurotrophic factor (BDNF) gene were analyzed.

Results: Of the 97 CpG sites in the BDNF gene, only 4 displayed significant methylation differences between AUD cases and controls with the employment of a Bonferroni p-value correction. To obtain more accurate results of overall methylation, CpG sites were grouped according to gene loci (Promoter, 5’UTR, first exon, gene body, and 3’UTR). Only the gene body of the BDNF gene approached significance (p=0.093) for a difference in methylation between AUD cases and controls with AUD cases being slightly hypomethylated.

Conclusion: No BDNF gene regions were found to be differentially methylated in the AUD group. This could be due to the small and homogenous sample. However, one CpG region in the gene body approached statistical significance. Overall, gene body methylation is important for splicing kinetics. This may lead to different BDNF mRNA transcripts being produced between AUD cases and controls which can affect the half-life of BDNF mRNA. Future research is needed to examine this possibility in a larger study.