Barrett

Barrett, The Honors College at Arizona State University proudly showcases the work of undergraduate honors students by sharing this collection exclusively with the ASU community.

Barrett accepts high performing, academically engaged undergraduate students and works with them in collaboration with all of the other academic units at Arizona State University. All Barrett students complete a thesis or creative project which is an opportunity to explore an intellectual interest and produce an original piece of scholarly research. The thesis or creative project is supervised and defended in front of a faculty committee. Students are able to engage with professors who are nationally recognized in their fields and committed to working with honors students. Completing a Barrett thesis or creative project is an opportunity for undergraduate honors students to contribute to the ASU academic community in a meaningful way.

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Early Life Stress: An Increased Risk of Schizophrenia through Activation of the Complement Component Pathway

Description
Schizophrenia is a debilitating psychiatric disorder with poorly understood genetic and environmental factors. An allelic variant of complement component 4 (C4), a protein first identified in innate immune response is strongly associated with schizophrenia. In the brain, activity of C4 leads to dendritic pruning, a process that may…

Schizophrenia is a debilitating psychiatric disorder with poorly understood genetic and environmental factors. An allelic variant of complement component 4 (C4), a protein first identified in innate immune response is strongly associated with schizophrenia. In the brain, activity of C4 leads to dendritic pruning, a process that may be causal in disease progression. Environmental factors, such as early life exposure to significant stressors also associate with increased risk of schizophrenia in later life. My hypothesis is that these factors do not act independently, but rather in tandem to influence disease etiology.
This hypothesis is supported by previous studies demonstrating that stress-induced elevation of glucocorticoids increases the transcription of C4. I propose that activated glucocorticoid receptors directly increase C4 protein expression as a transcription factor activator. Additionally, I propose that activated glucocorticoid receptors inhibit the expression of the transcription factor nuclear factor-light-chain-enhancer of activated B cells (NF-κB), thereby leading to decreased expression of the C4 inhibitor CUB and Sushi multiple domains 1 (CSMD1).
Glucocorticoid receptors and C4 are richly expressed in the hippocampus, a region critical in memory consolidation, spatial, and declarative memory. I propose that stress-induced upregulation of C4 activity in the hippocampus promotes excessive synaptic pruning, contributing to specific deficits and hippocampal shrinkage seen in schizophrenia. Stress exposure during fetal development and adolescence likely acts through the proposed mechanisms to increase hippocampal C4 activity and subsequent schizophrenia risk. These mechanisms may reveal novel interactions between environmental and genetic risk factors in the etiology of schizophrenia through complement activation.
ContributorsHoegh, Emily Marie (Author) / Orchinik, Miles (Thesis director) / Newbern, Jason (Committee member) / Talboom, Joshua (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05