Scientists have discovered that aging immune cells may hold a hidden blood-based clue to detecting depression.
Scientists have discovered that the biological aging of certain white blood cells may provide an important clue to depression, potentially opening the door to a blood test that could help identify the condition.
The study found that measuring how quickly these immune cells age can help predict emotional and cognitive symptoms of depression, including hopelessness and loss of pleasure. Interestingly, the same biological markers were not associated with physical symptoms such as fatigue or changes in appetite.
Published in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, the findings could bring scientists closer to developing an objective biological marker for depression, a mental health condition that affects nearly one in five US adults.
Why Depression Is So Difficult to Detect
Doctors currently diagnose depression primarily by evaluating symptoms reported by patients. Although blood tests may help eliminate other possible medical explanations, there is still no established biological test that can reliably identify depression or detect its earliest signs.
Part of the challenge is that depression does not affect everyone in the same way. Some people develop physical (or somatic) symptoms, including exhaustion, reduced appetite, or agitation. Others experience changes in thinking and mood, such as persistent hopelessness or anhedonia, a condition characterized by an inability to experience pleasure or maintain interest in activities that were once enjoyable.
“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 study author Nicole Beaulieu Perez, assistant professor at NYU Rory Meyers College of Nursing. “Our study reveals unique biological underpinnings of mental health that are often obscured by broad diagnostic categories.”
Why Researchers Studied Women With HIV
Depression occurs more frequently among people living with certain conditions that affect the immune system, including HIV. Several overlapping factors may contribute to this increased risk, such as ongoing inflammation, social stigma, and socioeconomic challenges.
Women living with HIV face particularly high rates of depression. When depression goes untreated or unrecognized, it can interfere with their ability to participate in medical care and consistently take antiretroviral medications, which are essential for managing HIV.
“For women with HIV who may be experiencing depression, we want to better understand what’s going on and catch it earlier so that it doesn’t harm their whole overall health,” said Perez.
To investigate possible biological connections between depression and HIV, the research team focused on accelerated biological aging. Previous studies have linked this process to both conditions.
Unlike chronological age, which simply counts the years since a person was born, biological age reflects changes occurring within the body over time. Researchers can estimate biological age using tools known as “epigenetic clocks,” which analyze chemical changes to DNA. These modifications can influence how genes function without altering the underlying genetic code.
Blood Samples Reveal a Surprising Depression Link
The researchers examined information from 440 participants in the Women’s Interagency HIV Study, including 261 women living with HIV and 179 women without the infection.
To evaluate depression, they used the Center for Epidemiologic Studies Depression Scale (CES-D), a standardized 20-item questionnaire designed to assess both physical and nonphysical symptoms.
Blood samples were then analyzed using two different epigenetic clocks. One estimated biological aging across multiple types of cells and tissues, while the other focused specifically on monocytes, a type of white blood cell involved in the body’s immune defenses.
Monocytes help the immune system respond to infections and other threats. They are especially important in HIV infection, and previous research has found elevated monocyte levels in people experiencing depression.
The results revealed a notable difference between the two aging measures.
Biological aging in monocytes was associated with nonphysical depression symptoms, particularly anhedonia, hopelessness, and feelings of failure. This relationship appeared in women both with and without HIV.
However, the same aging measure was not associated with physical symptoms of depression.
“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,” said Perez.
The broader epigenetic clock, which measured aging across multiple cell and tissue types, showed no association with depression symptoms.
These differences suggest that examining biological aging in specific immune cells may reveal connections to mental health that are missed when researchers measure aging more generally.
Could a Blood Test Transform Depression Diagnosis?
Although the findings are promising, Perez emphasized that additional research is necessary before measurements of immune cell aging can become part of routine depression diagnosis or treatment.
The study identifies a potential biomarker, but it does not establish a clinically validated blood test for depression. Researchers will need to investigate the relationship further and determine how reliably these biological signals can identify depression across different populations.
Eventually, such a test could complement traditional mental health assessments, potentially helping clinicians recognize depression sooner and tailor treatment to individual patients.
One possible application would be using a person’s biological profile to help predict which antidepressant medication is most likely to be effective. This could reduce some of the uncertainty involved in finding appropriate treatment.
“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,” said Perez. “Our findings bring us a step closer to this goal of precision mental health care, especially for high-risk populations, by providing a biological framework that could guide future diagnosis and treatment.”
Reference: “Monocyte epigenetic age acceleration is linked to non-somatic depressive symptoms in women with and without HIV” by Nicole Beaulieu Perez, Ke Xu, Yanxun Xu, Lang Lang, Kathryn Anastos, Maria L Alcaide, Mardge Cohen, Sadeep Shrestha, Andrew Edmonds, Jacquelyn Meyers, Seble Kassaye, Igho Ofotokun, Gypsyamber D’Souza, Bradley Aouizerat and Leah H Rubin, 11 May 2026, The Journals of Gerontology: Series A.
DOI: 10.1093/gerona/glag083
Additional study authors include Ke Xu of Yale University; Yanxun Xu, Lang Lang, Gypsyamber D’Souza, and Leah Rubin of Johns Hopkins University; Kathryn Anastos of Albert Einstein College of Medicine; Maria Alcaide of the University of Miami Miller School of Medicine; Mardge Cohen of Stroger Hospital of Cook County Health System; Sadeep Shrestha of the University of Alabama at Birmingham; Andrew Edmonds of UNC Chapel Hill; Jacquelyn Meyers of Downstate Health Sciences University; Seble Kassaye of Georgetown University; Igho Ofotokun of Emory University; and Bradley Aouizerat of NYU.
Funding for the research was provided by the National Institute of Mental Health (F32MH129151, P30MH075673) and the National Institute on Minority Health and Health Disparities (K08MD019998).
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