Defense Date
2026
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Integrative Life Sciences
First Advisor
Elizabeth Prom-Wormley
Second Advisor
Roseann Peterson
Abstract
Psychosis is a complex psychiatric phenotype characterized by substantial heterogeneity in symptom presentation, psychosis diagnosis, comorbidity patterns, and genetic architecture across diverse populations in the general population. Despite advances in psychiatric epidemiology and genomics, important gaps remain in understanding how psychosis symptoms and psychosis-related diagnoses manifest across racial and ethnic groups and how evolutionary genomic factors may contribute to disease risk and cross-ancestry genetic prediction. This dissertation, Characterizing Comorbidity in Psychosis in the General Population, integrates epidemiological, psychometric, and evolutionary genetic approaches to examine psychosis across diverse populations.
Aim 1 examined racial and ethnic differences in psychosis comorbidity patterns using data from the Collaborative Psychiatric Epidemiology Surveys (CPES). Multinomial logistic regression analyses were conducted to evaluate associations between psychosis symptoms and co-occurring mood, anxiety, and substance use disorders across racial and ethnic groups. Results demonstrated significant heterogeneity in psychosis presentation, with Black and Hispanic participants more likely to report isolated a psychosis diagnosis, while White participants more frequently demonstrated psychosis diagnosis comorbid with mood and anxiety disorders.
Aim 2 evaluated the latent structure and measurement invariance of psychosis symptoms across racial and ethnic groups using confirmatory factor analysis with categorical indicators. A two-factor model distinguishing hallucinations and delusions provided better fit than a single-factor model. Multi-group analyses supported configural and threshold-loading invariance across groups, suggesting that core psychosis symptom constructs were measured comparably despite observed differences in prevalence and symptom clustering.
A review synthesized the use of comparative genomics, conservation metrics, and population genetic approaches in understanding disease-associated variation and highlighted methodological challenges in applying evolutionary frameworks to complex psychiatric traits.
Aim 4 investigated the evolutionary and functional genetic architecture of psychosis-associated loci using summary statistics from Psychiatric Genomics Consortium (PGC) and Genomics Psychiatry Cohort datasets and population genetic data from the 1000 Genomes Project. Analyses incorporated conservation metrics including PhyloP, Tajima’s D, and sequence constraint measures to evaluate enrichment of psychosis-associated variation in evolutionarily conserved regions across ancestries. Results indicated that conserved genomic regions explained a disproportionate share of psychosis heritability, although enrichment patterns varied across populations and did not fully resolve limitations in cross-ancestry polygenic risk score portability.
Collectively, these findings demonstrate that psychosis symptoms and psychosis-related diagnoses in the general population reflect both shared and population-specific patterns of symptom structure, comorbidity, and genetic architecture. This work contributes to psychiatric genetics and mental health disparities research by integrating epidemiological and evolutionary approaches to better characterize psychosis across diverse populations and by identifying important considerations for future cross-ancestry genomic studies and polygenic risk prediction efforts.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-7-2026