A study of 440 participants from the Women’s Interagency HIV Study found that accelerated epigenetic aging in monocytes—an immune cell type—tracked more closely with emotional and cognitive depression symptoms such as hopelessness and loss of pleasure than with physical symptoms like fatigue. The work, published in The Journals of Gerontology: Series A, adds evidence that cell-type-specific aging measures could contribute to future biological tools to complement symptom-based depression screening, though researchers say more validation is needed before clinical use.
A blood-based measure of “biological aging” in a specific immune cell type may be associated with particular depression symptoms, according to research released by New York University and published in The Journals of Gerontology: Series A: Biological Sciences and Medical Sciences.
The researchers analyzed DNA methylation patterns—chemical modifications to DNA commonly used in so-called epigenetic clocks—to estimate age acceleration in monocytes, a type of white blood cell involved in immune responses. In the analysis, faster monocyte epigenetic aging was linked to non-somatic (emotional and cognitive) symptoms of depression, including anhedonia (loss of pleasure), hopelessness and feelings of failure.
The study drew on data from 440 women in the Women’s Interagency HIV Study (WIHS), including 261 women living with HIV and 179 women without HIV. Depression symptoms were measured using the Center for Epidemiologic Studies Depression Scale (CES-D), a 20-item questionnaire that includes both somatic symptoms (such as fatigue and appetite changes) and non-somatic symptoms.
Researchers compared two kinds of epigenetic aging measures: one designed to reflect aging across multiple cell types and tissues, and another designed to estimate monocyte-specific biological age. The report said the broader, multi-cell-type clock was not associated with depression symptoms in the same way, while the monocyte-focused measure showed the strongest relationship with non-somatic symptom scores.
“Depression is not a one-size-fits-all disorder -- it can look really different from person to person, which is why it's so important to consider varied presentations and not just a clinical label,” said Nicole Beaulieu Perez, an assistant professor at NYU Rory Meyers College of Nursing, in the university’s release.
Perez also highlighted why focusing on symptom subtype may matter for people with chronic illness, including HIV.
“This is particularly interesting because people with HIV often have physical symptoms like fatigue that are attributed to their chronic illness rather than a depression diagnosis. But this flips that on its head because we found that these measures are associated with mood and cognitive symptoms, not somatic symptoms,” she said.
The NYU release described depression as more common among people with immune-related conditions such as HIV and attributed elevated risk to factors including chronic inflammation, stigma and economic challenges—pressures that can also affect engagement in care and medication adherence.
The researchers cautioned that the findings do not establish a diagnostic test for depression and that further research is needed before such measures could be used clinically. Still, they argued that biological measures might one day complement patient-reported symptoms and help move toward earlier and more tailored care.
“I think about the adage, 'What gets measured gets managed.' An aspirational goal in mental health would be to combine subjective experience with objective biological testing,” Perez said.
