Childhood trauma in women with HIV is associated with increased mitochondrial respiration despite reduced mitochondrial DNA copy number.

Early life stress (ELS) is highly prevalent among women with HIV (WWH) and contributes to risk for brain health disorders. Mitochondria represent key regulators of cellular stress processes and may represent a key mechanism linking ELS to biological vulnerability. While mitochondrial dysfunction has been associated with ELS in other populations, it remains unknown whether ELS is related to multidimensional mitochondrial health in WWH. Thus, we examined associations between ELS and mitochondrial health metrics in WWH. Sixty-one WWH completed the Childhood Trauma Questionnaire (CTQ) and provided blood samples. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated and used to assess mitochondrial bioenergetic function (Seahorse Cell Mito Stress Test), mitochondrial DNA copy number (mtDNAcn, qPCR), mtDNA integrity (qPCR), cell free mitochondrial DNA (cf-mtDNA, qPCR), and static mitochondrial protein expression (western blots). Linear regression models were used to evaluate associations between CTQ scores and mitochondrial outcomes. Higher CTQ scores were associated with increased basal respiration (β = 0.824, p = 0.012, q = 0.028), maximal respiration (β = 3.716, p = 0.014, q = 0.028), and spare respiratory capacity (β = 2.844, p = 0.026, q = 0.031). Conversely, higher CTQ scores were associated with lower mtDNAcn (β = - 2.369, p = 0.009, q = 0.018). No associations were observed with mtDNA integrity, cf-mtDNA, or mitochondrial protein expression. These findings demonstrate a divergent mitochondrial phenotype in WWH exposed to ELS, characterized by increased respiratory activity despite reduced mtDNA copy number. Mitochondrial health is potentially an integral consideration for understanding the link between ELS and biological vulnerability.