A stressful year leads to anxiety . Lasting isolation gives way to depression . An old trauma nags until it becomes paralyzing. Psychological and social experiences shape the brain, potentially leading to mental health issues. But the underlying mechanisms—how these experiences translate to physiological changes in the brain —remain poorly understood.
Now, psychological scientists may have found a missing link.
"We actually have biomarkers that really are showing links between psychological processes and people's physiology," said Christopher Fagundes, a professor of psychological sciences at Rice University.
In a review published in Current Directions in Psychological Science , Fagundes and his colleagues argue that the missing link might be mitochondria—those bean-shaped organelles from high school biology class.
Mitochondria are best known as the powerhouses of the cell for their role in generating energy. But they are now being recognized for many more roles, including their part in immune signaling, stress responses, and neural functioning. They are sensitive to environmental changes and social conditions, suggesting stress, loneliness, and trauma may target mitochondria, leading to downstream psychological effects. Alterations in mitochondrial function have been linked to anxiety, depression, post-traumatic stress disorder (PTSD), Alzheimer's disease, and other neurological disorders, as well as physical health outcomes such as cardiovascular diseases, diabetes, and certain cancers.
"The actual cellular machinery that links these experiences to disease really starts at the level of the mitochondria," said Fagundes, in an interview with the Observer. "Everything from the things we think of in terms of oxidative stress, to fatigue we feel, to the byproducts that come when stressors get out of control, it really is at the root of that."
The brain's high energy demand makes it particularly vulnerable to mitochondrial dysfunction. If mitochondria are less efficient, there is less energy for neurotransmission and plasticity, affecting processes that support mood regulation and memory . Variations in mitochondrial DNA—which helps control mitochondrial function—are associated with a greater risk for anxiety and depression.
Mitochondria may also be the link between stress, inflammation, and a number of mental health and cognitive disorders. Chronic stress gradually reduces mitochondrial efficiency, leading to disrupted energy balance, increased inflammation, and impaired brain signaling, which may help explain how stress can lead to fatigue, cognitive difficulties, and mood disturbances. Differences in mitochondrial function may also help explain why some people are more vulnerable to stress than others.
"A lot of the relationships that we've been thinking of—[between] inflammatory processes and these kinds of mental health outcomes—we should look toward alterations in mitochondria being a real mediator or [underlying] mechanism," said Fagundes.
The good news is that mitochondria are not only vulnerable to stressors but may be responsive to interventions that promote mitochondria resilience. If mitochondria are at the heart of this feedback loop, increasing their efficiency may help increase energy, reduce inflammation, and improve brain signaling.
Exercise, particularly endurance training, has the strongest and most consistent evidence for improving mitochondrial function. Aerobic exercise improves mitochondrial enzyme activity and mitochondrial number and may be one pathway linking exercise to improved mental and physical health (San-Millán, 2023).
Other interventions show potential. An intensive mindfulness program reduced anxiety and altered mitochondrial activity, but other stress markers remained unchanged (Gomutbutra et al., 2022). Psychotherapy increased mitochondria numbers in patients with PTSD, but these changes didn't correlate with symptom improvement (Hummel et al., 2023). Although mindfulness and psychotherapy may improve mitochondrial function, more studies are needed to support these preliminary results.
Combatting loneliness may also be a potential target to improve mitochondria and stave off other diseases.
"When people are lonely and socially isolated, a lot of times there seems to be this loop where then they have more anxiety to go out of the house," said Fagundes. "That is a recipe for negative alterations in the mitochondria, less energy, less resources to expend. So, when one does try to break that cycle, it's much more difficult."
As of now, few studies have examined the effects of improving social support on mitochondrial function. More research into this and other ways to improve mitochondria resilience—and the various roles mitochondria play in the brain—may be the key to better understanding and developing better treatment for a variety of mental and physical disorders.
As a field, "We've been talking a lot about things like inflammation. It tells us something is happening, but mitochondria help us explain why it's happening at the cellular level," said Fagundes. "If we focus more at the cellular level, we'll have a much deeper understanding of underlying processes."
References
Fagundes, C. P., Wu-Chung, E. L., & Heijnen, C. J. (2025). Psychological science at the cellular level: Mitochondria's role in health and behavior. Current Directions in Psychological Science.
Gomutbutra, P., Srikamjak, T., Sapinun, L., Kunaphanh, S., Yingchankul, N., Apaijai, N., Shinlapawittayatorn, K., Phuackchantuck, R., Chattipakorn, N., & Chattipakorn, S. (2022). Effect of intensive weekend mindfulness-based intervention on BDNF, mitochondria function, and anxiety. A randomized, crossover clinical trial. Comprehensive Psychoneuroendocrinology, 11, Article 100137.
Hummel, E. M., Piovesan, K., Berg, F., Herpertz, S., Kessler, H., Kumsta, R., & Moser, D. A. (2023). Mitochondrial DNA as a marker for treatment-response in posttraumatic stress disorder . Psychoneuroendocrinology, 148, Article 105993.
San-Millán, I. (2023). The key role of mitochondrial function in health and disease. Antioxidants, 12(4), Article 782.
