Monocyte Epigenetic Age Acceleration is Linked to Non-Somatic Depressive Symptoms in Women with and Without HIV

Depression disproportionately affects women living with HIV, yet symptom heterogeneity and the lack of observable biomarkers can impede detection. Accelerated aging of monocytes-key innate immune cells-may contribute to depression, particularly in this population. A DNA methylation clock, MonoDNAmAge, estimates monocyte biological age and has shown evidence of epigenetic age acceleration (EAA) in women with HIV. Here, we examine MonoDNAmAge as a biomarker of depression in women with and without HIV, differentiating non-somatic from somatic symptom domains. DNA methylation data and Center for Epidemiologic Studies Depression Scale (CES-D) scores were available from 440 Women's Interagency HIV Study participants. Two biological age estimates (HorvathDNAmAge and MonoDNAmAge) were calculated and orthogonalized with chronological age. In the total sample and subsamples stratified by HIV status, we used multiple linear regression to assess how EAAMono and EAAHorvath were associated with depressive symptoms. Standardized β coefficients are reported. The sample included 261 women with HIV (mean chronological age = 43.7 (8.9) years; 38% Black; 48% Hispanic) and 179 women without HIV (mean chronological age = 39.5 (10.0) years; 31% Black; 49% Hispanic). In the overall sample, EAAMono was associated with the non-somatic depressive symptom domain (β = 0.125, p = 0.018), and anhedonia specifically (β = 0.354, p = 0.007), adjusting for HIV, race, and ethnicity. This pattern persisted in the subsample with HIV (β = 0.112, p = 0.085). EAAHorvath was not associated with depression severity or symptom domains. Monocyte aging may represent a sensitive biomarker of non-somatic depression symptoms in women with HIV. The dynamics of monocyte aging and depression warrant further study to clarify mechanistic links.