Graduation Year
2024
Document Type
Thesis
Degree
M.S.P.H.
Degree Name
MS in Public Health (M.S.P.H.)
Degree Granting Department
Public Health
Major Professor
Monica Uddin, Ph.D.
Committee Member
Derek Wildman, Ph.D.
Committee Member
Chengqi Wang, Ph.D.
Keywords
depression, epigenetics, differential methylation, community-based cohorts
Abstract
Major depressive disorder (MDD) is a common and debilitating disorder that affects millions of people worldwide. MDD is a multifactorial disease with no established mechanism currently able to explain all facets of the disease or its etiology. Feedback loop mechanisms have been posited to explain the interactions of psychological and physical components of the disease etiology. Epigenetics, specifically DNA-methylation analyses, can shed light on the interaction between the within-person environment resulting from MDD symptomology, the persistence of the disease, and factors influencing remission. Here, a differentially methylated region analysis was conducted using samples derived from whole blood to interrogate the distinctions in epigenetic modifications among individuals currently experiencing, never having experienced, and in a state of remission from MDD in a predominantly African-American discovery cohort. The study participants (n=31 currently have MDD, n=41 remitted MDD, and n=72 have never had MDD) are a subsample from a larger prospective, longitudinal study, the Detroit Neighborhood Health Study. The replication cohort used to validate results consisted of a subsample of participants from the Grady Trauma Project (current MDD (n = 31), remitted MDD (n=41), and never having had MDD (n=72), using both targeted and de novo analyses. Differentially methylated region analyses were completed investigating three disease state comparisons: never vs. current, never vs. remitted, and current vs. never. A total of 134 DMRs were found among these comparisons in the discovery cohort, 11 of which were found within the replication cohort. Five DMRs, BCOR, SLFN12, CPT1B, PM20D1, and PRDM8, were differentially methylated among all three disease state comparisons. Gene set enrichment analysis was performed for significant DMRs in the DNHS cohort, implicating pathways related to regulatory pathways, metabolism, bone health, energy synthesis, neuroinflammation signaling, and the immune response. Several DMRs within both the never vs. remitted and never vs. current analyses were found to have effect sizes of opposite directions, which may suggest changes characteristic of remission. One gene in particular, PRDM8, was present across all three discovery analyses and, notably, exhibited consistent effect size directionality between the discovery analysis group and its associated replication group (never vs. current). These findings help to better inform our understanding of the interplay between epigenetic regulation and the physiological systems involved in MDD and underscore the importance of epigenetic regulation in MDD progression and remission, prompting further inquiry.
Scholar Commons Citation
Mullins, Lanie KateLynn, "A Differentially Methylated Region Analysis Between Three Disease States of Major Depressive Disorder in Primarily African-American Cohorts" (2024). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/10226
