Psychiatry and Psychology Commons^™

Examination Of Common And Rare Variant Genetic Architecture Of Psychiatric Disorders, Mohammad Ahangari

Theses and Dissertations

Psychiatric disorders are often heterogenous in their manifestation and genome-wide association studies have identified many common risk variants involved in their polygenic architectures with varying degrees of pleiotropy. In recent years, large-scale biobanks have also begun sequencing the genome of their participants to elucidate the role of rare risk variation in the genetic architecture of complex phenotypes, including psychiatric traits. This dissertation sought to better understand the role of both common and rare risk variation in the genetic architecture of psychiatric disorders with a particular focus on schizophrenia and alcohol problems. In the first three analyses, we focused on characterizing …

Molecular Brain Adaptations To Ethanol: Role Of Glycogen Synthase Kinase-3 Beta In The Transition To Excessive Consumption, Andrew D. Van Der Vaart

Theses and Dissertations

Alcoholism is a complex neuropsychiatric disease that is characterized by compulsive alcohol use and intensifying cravings and withdrawals, often culminating in physiologic dependency. Fundamental alterations in brain chemistry underlie the transition from initial ethanol exposure to repetitive excessive use. Key mediators of this adaptation include changes in gene expression and signal transduction. Here we investigated gene expression pathways in prefrontal cortex and nucleus accumbens following acute or chronic ethanol treatment, to identify genes with potentially conserved involvement in the long-term response of the corticolimbic system to repeated ethanol exposure. We investigated Gsk3b, which encodes glycogen synthase kinase 3-beta, as a …

The Dual Faces Of Misery, Arden Moscati

Theses and Dissertations

Major Depression (MD) and Generalized Anxiety Disorder (GAD) are psychiatric disorders that arise from dysfunction of the core human capacities for emotion. Sapience is inextricably bound up with the potential for feelings of regret, worry and concern. When these emotions lead to clinically significant impairment or distress, they may result in one or both of the disorders of MD and GAD. The occurrence of MD and GAD in the same person, known as comorbidity, is remarkably high; substantially higher than would be expected by chance.

MD and GAD have been studied since the mid-20^th century, resulting in a substantial …

Identifying Functional Variation In Schizophrenia Gwas Loci By Pooled Sequencing, Erik Loken

Theses and Dissertations

Schizophrenia demonstrates high heritability in part accounted for by common simple nucleotide variants (SNV), rare copy number variants (CNV) and, most recently, rare SNVs Although heritability explained by rare SNVs and CNVs is small compared to that explained by common SNVs, rare SNVs in functional sequences may identify specific disease mechanisms. However, current exome methods do not capture a large proportion of potentially functional bases where rare variation may impact disease risk: as much as two-thirds of conserved sequences lie outside the exome in non-coding regions of cross-species evolutionary constraint. We reasoned that the candidate loci from the Psychiatric Genomics …