Biomedical Sciences ETDs

Publication Date

5-1-2010

Abstract

Alcohol dependence (AD) is a complex addictive disorder, affecting 5.4% of the general population during a lifetime (Kessler, 2005) and has a complex heterogenous phenotype, with behavioral, morphological, and genetic components. Alcohol use can cause gray matter and white matter tissue damage. The extent of alcoholisms effect on brain matter structure in young adults is less known. Assessement of low and high alcohol dependent individuals was derived from DSM-IV. FSL based Magnetic Resonance Imaging (MRI) and quantitative fiber tracking derived from diffusion tensor imaging (DTI) assessed morphological alterations of 6 gray matter structures involved in addiction and 10 white matter structures that show connectivity of these structures in 26 low AD and 19 high AD individuals. Candidate SNPs were chosen relating to synaptic plasticity and myelination (BDNF, NTRK2, NFKB1, MAG, OLIG2) and each individual was genotyped. Alcohol dependence affected the volumes of the caudate-putamen, the accumbens, the amygdala and the hippocampus. The uncinate fasciculus was also affected by level og AD, showing smaller mean diffusivity (MD), quantified separately for axial diffusivity (AxD), a marker of axonal intergrity, and radial diffusivity (RD), a marker of myelin integrity. Exploratory associations of AD, morphological alterations and SNPs, showed significant correlations and trends, but was not well defined due to a small subject population. The present research shows evidence that behavioral diseases are associated with identifiable neuroanatomic alterations, and do form relationships with specific SNPs. Additional information is needed when studying a specific, yet multifactorial disease, such as AD, but nonetheless, we advocate the use of neuroimaging measures in genetic studies.

Keywords

Alcohol Dependence, Neuroimaging, Magnetic Resonance Imaging, Diffusion Tensor Imaging, Genetics, Single Nucleotide Polymorphsims

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Advisor

Perrone-Bizzozero, Nora

Second Advisor

Hutchison, Kent

First Committee Member (Chair)

Allan, Andrea

Second Committee Member

Wilson, Michael

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