This simple blood test might detect depression before symptoms appear

 

Blood tests that track how certain white blood cells age may help identify depression by focusing on emotional and cognitive symptoms rather than physical ones.

The research, published in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, moves scientists closer to finding a reliable biological marker for depression, a condition that affects nearly one in five adults in the United States.

Blood-Based Clues Could Improve Depression Diagnosis

Today, depression is diagnosed based on what patients report about their symptoms. Doctors may order lab tests to rule out other illnesses, but there is still no objective biological test that can confirm depression or detect it early.

Part of the challenge is that depression does not look the same for everyone. While some people experience physical (or somatic) symptoms such as fatigue, appetite changes, or restlessness, others mainly struggle with emotional and cognitive effects. These can include hopelessness, difficulty thinking clearly, or anhedonia -- the inability to feel pleasure and loss of interest in previously enjoyed activities.

"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."

Depression, Immune Health, and HIV

Depression is especially common among people with immune-related conditions such as HIV. This higher risk may stem from a combination of chronic inflammation, social stigma, and economic challenges. Women living with HIV are particularly affected, and depression can interfere with their ability to stay engaged in care and consistently take antiretroviral medications.

"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.

Studying Biological Aging With Epigenetic Clocks

To better understand the biology behind depression, researchers examined signs of accelerated aging in the body. Biological age, which does not always match a person's chronological age, can be estimated using "epigenetic clocks." These tools measure chemical changes to DNA that occur over time.

The study included 440 women -- 261 living with HIV and 179 without HIV -- from the Women's Interagency HIV Study. Depression symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D), a 20-item questionnaire that evaluates both somatic and non-somatic symptoms.

Blood samples were also analyzed to measure biological aging using two types of epigenetic clocks. One assessed aging across multiple cell types and tissues, while the other focused specifically on monocytes, a type of white blood cell involved in immune responses. Monocytes play an important role in HIV infection and are often elevated in people with depression.

Aging Immune Cells Linked to Emotional Symptoms

The findings showed that aging in monocytes was strongly associated with non-somatic symptoms of depression. These included anhedonia, feelings of hopelessness, and a sense of failure, in both women with and without 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," said Perez.

In contrast, the broader epigenetic clock that measured multiple cell types did not show a link to depression symptoms.

Toward Earlier Detection and Personalized Treatment

Perez emphasized that more research is needed before these findings can be used in clinical care. Still, the results point to a future where depression could be detected earlier and more precisely through biological testing.

Such advances could eventually support more personalized treatment approaches, including identifying which medications are most likely to work for a specific individual.

"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."

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.

The research was supported by the National Institute of Mental Health (F32MH129151, P30MH075673) and the National Institute on Minority Health and Health Disparities (K08MD019998).

Journal Reference:

1. 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, Leah H Rubin. Monocyte Epigenetic Age Acceleration is Linked to Non-Somatic Depressive Symptoms in Women with and Without HIV. The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, 2026; DOI: 10.1093/gerona/glag083

Courtesy:

New York University. "This simple blood test might detect depression before symptoms appear." ScienceDaily. ScienceDaily, 4 May 2026. <www.sciencedaily.com/releases/2026/05/260504023827.htm>.

 

 

 

 

 

MIT scientists discover millions of “silent synapses” in the adult brain

 

MIT neuroscientists have uncovered a surprising feature of the adult brain. It contains millions of "silent synapses," which are immature connections between neurons that remain inactive until they are needed to help form new memories.

For many years, scientists believed these silent synapses existed only during early development, when the brain is rapidly learning about the world. But the MIT team found that in adult mice, roughly 30 percent of synapses in the brain's cortex are still silent. This suggests the adult brain holds a large reserve of unused connections that can be activated when new information arrives.

Researchers say this hidden pool of synapses may explain how the brain continues to learn throughout life without disrupting existing memories.

"These silent synapses are looking for new connections, and when important new information is presented, connections between the relevant neurons are strengthened. This lets the brain create new memories without overwriting the important memories stored in mature synapses, which are harder to change," says Dimitra Vardalaki, an MIT graduate student and the lead author of the study.

Mark Harnett, an associate professor of brain and cognitive sciences, is the senior author of the paper, published in Nature. Kwanghun Chung, an associate professor of chemical engineering at MIT, is also an author.

Rethinking How Memory Works in the Adult Brain

Silent synapses were first identified decades ago, mostly in young animals. During early development, they are thought to help the brain absorb large amounts of new information about the environment. In mice, scientists believed these synapses disappeared by about 12 days of age (equivalent to the first months of human life).

However, some researchers suspected they might persist into adulthood. Clues came from studies of addiction, which is often considered a form of maladaptive learning. These studies hinted that silent synapses could reappear or remain in the adult brain.

Theoretical work by neuroscientists Stefano Fusi and Larry Abbott also suggested the brain needs a mix of flexible and stable synapses. Some connections must be easy to change to support new learning, while others must remain steady to preserve long-term memories.

A Chance Discovery Using Advanced Imaging

The MIT team was not initially searching for silent synapses. They were following up on earlier work showing that dendrites, the branch-like extensions of neurons, process signals differently depending on their location.

To explore this further, the researchers measured neurotransmitter receptors along dendrites using a technique called eMAP (epitope-preserving Magnified Analysis of the Proteome). This method physically expands brain tissue, allowing scientists to label proteins and view them in extremely high detail.

During this imaging, the researchers noticed something unexpected.

"The first thing we saw, which was super bizarre and we didn't expect, was that there were filopodia everywhere," Harnett says.

Filopodia are tiny protrusions that extend from dendrites. Although they had been observed before, their function was unclear because they are so small and difficult to study with traditional tools.

Filopodia and the Signature of Silent Synapses

Using the eMAP technique, the team found filopodia across multiple regions of the adult mouse brain, including the visual cortex, at levels far higher than previously reported. These structures contained NMDA receptors but lacked AMPA receptors.

This detail is crucial. Active synapses typically have both receptor types, which work together to transmit signals using the neurotransmitter glutamate. NMDA receptors alone cannot pass electrical signals under normal conditions because they are blocked by magnesium ions. Without AMPA receptors, these connections remain electrically inactive, which is why they are called "silent."

Turning Silent Synapses On

To test whether these filopodia function as silent synapses, the researchers used a modified patch clamping technique. This allowed them to measure electrical activity at individual filopodia while simulating the release of glutamate.

They found that glutamate alone did not produce a signal unless the NMDA receptors were experimentally unblocked. This provided strong evidence that these structures behave as silent synapses.

The team then showed it is possible to activate, or "unsilence," these connections. By pairing glutamate release with an electrical signal from the neuron, AMPA receptors accumulated at the synapse. This transformed the silent connection into a fully functional one capable of transmitting signals.

Importantly, this process was much easier than modifying already active synapses.

"If you start with an already functional synapse, that plasticity protocol doesn't work," Harnett says. "The synapses in the adult brain have a much higher threshold, presumably because you want those memories to be pretty resilient. You don't want them constantly being overwritten. Filopodia, on the other hand, can be captured to form new memories."

A Brain That Is Both Flexible and Stable

These findings support the idea that the brain balances flexibility and stability by maintaining a reserve of highly adaptable synapses.

"This paper is, as far as I know, the first real evidence that this is how it actually works in a mammalian brain," Harnett says. "Filopodia allow a memory system to be both flexible and robust. You need flexibility to acquire new information, but you also need stability to retain the important information."

What This Means for Aging and Brain Health

The researchers are now investigating whether similar silent synapses exist in human brains. They also want to understand how these connections change with age or in neurological conditions.

"It's entirely possible that by changing the amount of flexibility you've got in a memory system, it could become much harder to change your behaviors and habits or incorporate new information," Harnett says. "You could also imagine finding some of the molecular players that are involved in filopodia and trying to manipulate some of those things to try to restore flexible memory as we age."

More recent neuroscience research has continued to explore how synaptic plasticity supports lifelong learning. Studies on aging brains suggest that reduced synaptic flexibility may contribute to memory decline, while work in neurodegenerative diseases like Alzheimer's points to disruptions in synapse formation and function. There is also growing interest in targeting synaptic mechanisms to improve cognitive resilience and learning capacity later in life.

Together, these findings paint a picture of the brain as far more dynamic than once believed. Rather than being fixed, it appears to maintain a hidden запас of connections, ready to be activated when new experiences demand it.

The research was funded by the Boehringer Ingelheim Fonds, the National Institutes of Health, the James W. and Patricia T. Poitras Fund at MIT, a Klingenstein-Simons Fellowship, and Vallee Foundation Scholarship, and a McKnight Scholarship.

Journal Reference:

1. Dimitra Vardalaki, Kwanghun Chung, Mark T. Harnett. Filopodia are a structural substrate for silent synapses in adult neocortex. Nature, 2022; 612 (7939): 323 DOI: 10.1038/s41586-022-05483-6

Courtesy:

Massachusetts Institute of Technology. "MIT scientists discover millions of “silent synapses” in the adult brain." ScienceDaily. ScienceDaily, 6 May 2026. <www.sciencedaily.com/releases/2026/05/260504211848.htm>.