Date of Award

8-10-2021

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Psychology

First Advisor

Jessica Turner

Second Advisor

Jingyu Liu

Third Advisor

Tricia King

Fourth Advisor

Vince Calhoun

Abstract

Current diagnoses of schizophrenia (SZ) and bipolar disorder (BD) are classified by phenomenological principles and clinical descriptions. The boundaries of the disorders are merging with accumulating shared genetic and brain mechanisms being uncovered. Imaging genetics is a useful tool to understand the impact of genetic variations on the brain. It also enables capturing the behavioral implication of those genes and associated brain alterations.

This study aimed to reveal the associations among sets of genetic variations, structural brain abnormalities, and clinical symptom profiles shared in schizophrenia and bipolar disorders by imaging genetics and multivariate approaches. First, we mapped the symptom profiles onto brain patterns. Distinct structural brain patterns guided with symptom profiles represented by positive and negative syndrome scale (PANSS), through parallel independent component analysis (pICA) were extracted. Brain patterns related to positive symptoms, mood, and apathy were discovered in SZ and BD. Second, we investigated the relationships of symptoms and brain patterns regardless of diagnostic categories by projecting each disorder’s structural brain and PANSS patterns into the other disorder group (e.g., projecting patterns from schizophrenia to bipolar and vice versa) to reassess the associations. The projected brain patterns showed associations with broad symptoms rather than the original PANSS patterns. Finally, we explored the potential shared genetic mechanisms behind symptom-brain patterns by investigating the effect of polygenic risk scores (PRS) from the Psychiatric Genomics Consortium (PGC). Both SZ and BD PRS were significantly associated with the positive symptom-related brain patterns in SZ. Higher genetic risks contributed to more severe gray matter concentration (GMC) reductions in the temporal regions of SZ patients, and it may lead to worse positive symptoms. Correspondingly, in the BD, both SZ and BD PRS were significantly associated with the mood symptom-related brain patterns. Higher risks contributed to more severe gray matter concentration (GMC) reductions in the frontal-temporal-parietal circuits with worse mood symptoms. The polygenic effects behind the apathy component may be subtle. The results helped improve the understanding of categories of psychotic disorders starting from schizophrenia and bipolar disorder. It may essentially contribute to the more precise diagnosis and treatment for heterogeneous populations with psychosis.

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