Monocyte Epigenetic Age Links to Depression Symptom Subtypes, With Nicole Perez, PhD

New data from the Women’s Interagency HIV Study (WIHS) suggest that monocyte-specific epigenetic aging may help distinguish biologically distinct subtypes of depression, particularly those characterized by non-somatic symptoms such as anhedonia and hopelessness. The findings contribute to a growing precision psychiatry effort aimed at moving beyond global diagnostic labels toward symptom-level biology.

The study included 440 participants, including 261 women living with HIV, with a mean age of 43.7 years. Investigators assessed epigenetic age acceleration (EAA) using 2 approaches: a monocyte-derived clock and a multi-tissue epigenetic clock (Horvath). Associations were evaluated across depressive symptom domains measured by the Center for Epidemiologic Studies Depression Scale (CES-D), rather than total scores alone.

Monocyte epigenetic age acceleration was significantly associated with non-somatic depressive symptoms (P = .018), with the strongest signals observed for anhedonia (P = .007) and hopelessness (P = .007). No associations were found for somatic symptoms, including fatigue or sleep disturbance, and the Horvath multi-tissue clock showed no significant associations with either total or domain-specific depressive symptoms.

In the third part of our interview, Nicole Beaulieu Perez, PhD, RN, PMHNP-BC, assistant professor at NYU Rory Meyers College of Nursing, described next steps before a marker like monocyte epigenetic age acceleration could be considered clinically actionable. She emphasized the need for replicated trials and to understand the dynamics of monocyte age acceleration in the monocyte-derived clock.

“Can we actually change it?” she wondered. “Is it more static? Is it more dynamic, and what is it actually going to take? Is it something that we can reasonably do with pharmacology or with lifestyle behavioral interventions? How malleable is it?”

Perez added that while epigenetics is often considered more malleable than genetic sequence and known to change over the course of life in response to environmental influences, its clinical manipulation remains unclear. It is not yet known how malleable epigenetic marks are or what the appropriate timing or dosing would be to meaningfully manipulate them.

“This is not a study that is going to change practice today,” Perez said. “We hope that it will offer a roadmap for other precision mental health studies and for us to really start thinking differently about these very broad diagnostic categories.”

Watch parts 1 and 2 of the interview with Perez here: Monocyte Aging Links to Non-Somatic Depression Symptoms, With Nicole Perez, PhD and Monocyte Clock Detects Depression Signals, With Nicole Perez, PhD, respectively.

Perez has no reported disclosures.

References

Perez NB, Xu K, Xu Y, et al. Monocyte Epigenetic Age Acceleration is Linked to Non-Somatic Depressive Symptoms in Women with and Without HIV. J Gerontol A Biol Sci Med Sci. Published online March 24, 2026. doi:10.1093/gerona/glag083