Can Two Blood Markers Reveal the Hidden Cost of Chronic Stress? New Clues from Psychiatric and Proteomic Research

What if two simple blood tests could help detect a silent form of stress-related undernourishment—before you lose weight, become frail, or fall ill?

A growing body of research suggests that two emerging biomarkers—CCL11 and GDF15—may offer just that kind of early warning. These molecules, tied to immune and mitochondrial stress, are increasingly being linked to aging, chronic disease, and diminished resilience.

A recent study published in the Journal of Psychiatric Research (2025) adds to the momentum. Researchers assessed serum levels of CCL11 (a pro-inflammatory chemokine) and GDF15 (a mitochondrial stress signal) in over 550 individuals with schizophrenia, bipolar disorder, or major depressive disorder, comparing them to healthy controls.

They found:

• CCL11 levels were significantly higher in patients with schizophrenia and bipolar disorder.

• GDF15 levels were elevated across all psychiatric groups, and both markers rose with increasing numbers of hospitalizations—a proxy for illness burden and progression.

Why does this matter?

Because these markers may reflect more than just psychiatric pathology. They could be windows into the deeper biology of stress-related aging and vulnerability, across both brain and body.

From Brain and Immune Stress to Systemic Aging

This study echoes findings from large-scale proteomic research, which shows that the most age-sensitive proteins in human blood often originate from the brain, immune system, and mitochondria—not just the liver or metabolic tissues.

Studies like those by Oh, H. S.-H., (2025), Lehallier et al. (2019), and Wingo et al. (2023) have mapped thousands of circulating proteins across the human lifespan, identifying consistent signatures that predict functional decline and resilience loss.

These include:

• Neuroinflammatory signals like CCL11, linked to impaired memory and brain aging

• Stress-responsive mitokines like GDF15, associated with appetite loss, mitochondrial failure, and increased mortality risk

In other words, aging and chronic disease aren’t just about wear and tear—they’re about how well our systems adapt to stress, and whether energy is available for repair and regeneration.

Connecting the Dots: Toward ERM Recognition

In our clinical work, we’ve been developing the concept of Exposure-Related Malnutrition (ERM)—a subtle but progressive condition that arises when chronic stress, inflammation, and environmental exposures overwhelm the body’s capacity to maintain itself.

Unlike classical malnutrition, ERM doesn’t always show up as weight loss or low albumin.

Instead, it hides in the background:

• Brain fog, immune dysfunction, fatigue, poor wound healing

• Normal labs, but a sense that “the system is running on fumes”

That’s why biomarkers like CCL11 and GDF15 are so exciting. They appear to capture the very trade-offs that define ERM—when energy is diverted away from long-term maintenance toward short-term survival.

Looking Ahead: Practical Applications

Imagine being able to:

• Screen for early ERM in high-risk individuals—those with chronic stress, long COVID, overtraining, or complex illness

• Stage biological resilience based on patterns of immune and mitochondrial strain

• Track recovery as interventions restore energy balance and reduce inflammation

We’re not quite there yet—but the science is catching up. The study on psychiatric patients is a powerful proof of concept: even before frailty or organ dysfunction appear, the body sends molecular distress signals. We just need to learn how to listen.

🌱 Final Thought

Resilience is not a mystery—it’s a measurable, adaptable state of balance. With tools like CCL11 and GDF15, we may be one step closer to recognizing when that balance begins to slip, and more importantly, how to restore it.

🔬 Want to Learn More?

Teixeira, A. L., Czepielewski, L. S., de Lima, L. S., Sartori, J., Panizzutti, B., Brietzke, E., & Gama, C. S. (2025). The effect of the number of psychiatric hospitalizations and diagnosis in serum levels of CCL11 and GDF15 in individuals with stable schizophrenia, bipolar disorder, and major depressive disorder: The compass between neuro and somatoprogression. Journal of Psychiatric Research. Advance online publication. https://doi.org/10.1016/j.jpsychires.2024.113345

Oh, H. S.-H., Le Guen, Y., Rappoport, N., Urey, D. Y., Farinas, A., Rutledge, J., Channappa, D., Wagner, A. D., Mormino, E., Brunet, A., Greicius, M. D., & Wyss‑Coray, T. (2025). Plasma proteomics links brain and immune system aging with healthspan and longevity. Nature Medicine. Advance online publication. https://doi.org/10.1038/s41591-025-03798-1 

Adela, Ramu, Banerjee, Sanjay K., GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective, Journal of Diabetes Research, 2015, 490842, 14 pages, 2015. https://doi.org/10.1155/2015/490842