Document Type



Doctor of Philosophy



Date of Defense


Graduate Advisor

Robert Paul, Ph.D. ABPP-CN


Carissa Philippi, PhD

Sandra Langeslag, PhD

Beau Ances, MD. Ph.D. MS.

Jodi Heaps-Woodruff, PhD


This study examined the interactive effects of early life stress (ELS) and HIV on brain morphometry, diffusion-basis-spectrum-imaging (DBSI), risky decision-making, and sex-risk behavior. 122 people with HIV (PWH) and 113 people without HIV (PWoH), free of major psychiatric illness and neurological confounds, were stratified into high (≥ 3 events) vs. low (< 3 events) ELS [PWoH/low ELS (n = 57), PWoH/high ELS (n =56), PWH/low ELS (n = 43), PWH/high ELS (n = 79)] and underwent structural magnetic resonance imaging, DBSI, neuropsychological, and risky-behavior assessment; all PWH were virologically controlled. Compared to PWoH, PWH had smaller orbitofrontal cortex (OFC), parietal lobes, insula, caudate and anterior cingulate. No ELS effects were detected in volumetric measures. Significant interactions were found between HIV serostatus and ELS on the OFC and on cellularity of the inferior fronto-occipital fasciculus after multiple comparisons adjustment. Specifically, PWH/high ELS exhibited significantly smaller OFC and PWoH/high ELS show significantly larger OFC than the other groups. PWoH/high ELS exhibited higher DBSI cellularity (neuroinflammation proxy) of the inferior-occipital-fasciculus compared to PWoH/high ELS. Regardless of HIV status, executive function moderated the relationship between the OFC and sex-risk behavior such that individuals within the sample who performed above average on a measure of executive function and had a larger OFC reported fewer sex partners in past six months than individuals with smaller volumes. No interaction was found between HIV serostatus and ELS on risky behavior measures. Clustering analyses defined ELS subgroups in PWH that were determined by demographic characteristics, duration of infection, recent CD4+ T-cell count, nadir CD4+ T-cell count and high/low ELS.Even in PWH that are virologically controlled, without major current psychiatric comorbidities, there is evidence of a synergistic impact of ELS and HIV on OFC volumes. Higher volumes in the OFC were detrimental when associated with lower executive function scores or advantageous when associated with higher executive function. Findings suggest that ELS is associated with different brain signatures among PWoH and virally suppressed PWH. However, ELS was not directly associated with risky behaviors, and subgroups in PWH were characterized by demographic variables, past substance use and HIV clinical variables.