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Medical Sciences

Virginia Commonwealth University

Theses and Dissertations

Schizophrenia

Publication Year

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Full-Text Articles in Medicine and Health Sciences

Exploring The Heteromeric Interface Of The 5-Ht2a-Mglu2 Receptor Complex, Mohamed Aarif Abdul Kareem Jan 2020

Exploring The Heteromeric Interface Of The 5-Ht2a-Mglu2 Receptor Complex, Mohamed Aarif Abdul Kareem

Theses and Dissertations

Schizophrenia is a serious mental disorder characteristic of several neurotransmitters including dopamine, serotonin, and glutamate being in imbalance. Early therapies focused solely on dopamine antagonism and second-generation antipsychotics focused on the dopamine and serotonin systems and their respective G protein coupled receptor (GPCR) proteins. Although debate for dimerization of certain classes of GPCR exist, the establishment of an mGlu2-5-HT2A heterocomplex, which is implicated in schizophrenia is of interest. Previous studies have used a mutation-based approach to identify transmembrane domain 4 (TM4) as the domain responsible in mGlu2 for mediating heteromerization before narrowing down the individual amino acids responsible for …


Validation Of Copy Number Variants Associated With Schizophrenia Risk In An Irish Population And Implications To Clinical Practice, Rachel L. Elves Jul 2013

Validation Of Copy Number Variants Associated With Schizophrenia Risk In An Irish Population And Implications To Clinical Practice, Rachel L. Elves

Theses and Dissertations

Schizophrenia is a complex disorder affecting 1% of the population and is highly heritable, but the majority of contributing genetic factors has remained elusive. Current risk estimates for clinical practice are primarily determined by family history and associated empirical risk. Copy number variants (CNVs) may hold the key to explaining the missing heritability in schizophrenia research; schizophrenia risk estimates as high as 30% have been found for the most-studied CNV associated with schizophrenia, 22q11. Currently, there are methods to identify CNVs though previously collected data from SNP microarrays that would facilitate these types of studies. To determine if algorithms that …


A Review Of Common And Rare Genetic Variants In Schizophrenia, Jonathan Luedders Jul 2011

A Review Of Common And Rare Genetic Variants In Schizophrenia, Jonathan Luedders

Theses and Dissertations

Genetic epidemiology has shown a large role for genetic influences on schizophrenia. However, the nature of the variants involved is debated. The common disease-common variant (CDCV) hypothesis suggests that schizophrenia is caused by common alleles with small effect sizes. According to the common disease-rare variant (CDRV) hypothesis, schizophrenia is caused by rare variants with large effect sizes. In recent years, evidence has been found for both common and rare variants in schizophrenia. Several SNPs have been associated with schizophrenia through genome-wide association studies (GWAS), supporting the CDCV hypothesis. In support of the CDRV hypothesis, individuals with schizophrenia have been found …


Expression Profiling And Functional Validation Of Micrornas Involved In Schizophrenia And Bipolar Disorder, Albert H. Kim Jul 2011

Expression Profiling And Functional Validation Of Micrornas Involved In Schizophrenia And Bipolar Disorder, Albert H. Kim

Theses and Dissertations

MicroRNAs (miRNAs) are a family of small non-coding RNAs that regulate gene expression at both the mRNA and protein levels. MiRNAs have been shown to affect neuronal differentiation, synaptosomal complex localization and synapse plasticity, all functions thought to be disrupted in schizophrenia. We investigated the expression of 667 miRNAs (miRBase v.13) in the prefrontal cortex of individuals with schizophrenia (SZ, N = 35) and bipolar disorder (BP, N =35) using a real-time PCR-based Taqman Low Density Array (TLDA). After extensive QC steps, 441 miRNAs were included in the final analyses. At a FDR of 10%, 22 miRNAs were identified as …


Genes And Symptoms Of Schizophrenia: Modifiers, Networks, And Interactions In Complex Disease, Sarah Bergen Sep 2009

Genes And Symptoms Of Schizophrenia: Modifiers, Networks, And Interactions In Complex Disease, Sarah Bergen

Theses and Dissertations

Understanding the genetic foundations of schizophrenia and the resultant symptom manifestations is an important step as we work toward development of new prevention and treatment strategies. This work has sought better understanding of this disease through use of three subject cohorts and two studies using simulated data exploring features of complex disease. First, we probed the symptoms of schizophrenia in subjects of African and European ancestry drawn from the Genetic Association Information Network (GAIN) schizophrenia study and found significant differences between groups, particularly in affective symptoms. The genetic basis of symptom variation was then explored in a selection of candidate …