Energy: Stress Shapes the Brains Power Supply, Nutrition Helps It Reset
- Moira Newiss
- Aug 29
- 10 min read
When we talk about stress, we usually picture racing thoughts, tense muscles, or a pounding heart. But stress doesn’t just live in our minds — it reaches all the way down to our cells. At the very core of this biology are mitochondria, the tiny powerhouses that generate energy for life itself.
Over the past decade, Dr. Martin Picard and colleagues at Columbia University in the US the have pioneered the field of mitochondrial psychobiology, showing how mitochondria act as central hubs linking psychological experiences to physical health. His work helps us understand how stress translates into disease, and why disorders as varied as chronic fatigue syndrome, depression, bipolar disorder, and schizophrenia may all share a common root: brain energy failure.
Simply put, we have mitochondria in our cells, they play a key role not only making the energy our body uses but also acting as a command and control centre or an information processing hub. Mitochondria are tiny little organelles in our cells and tissues that need a lot of energy can have millions of them per cell e.g. neurons. They are constantly communicating with each other and with other cells in our body through chemical messages, or molecules, that they make and release depending on what is going on in their environment.
Stress Through the Lens of Energy
Picard suggests that mitochondria are not passive fuel suppliers but active sensors and integrators of stress. This means that when we experience stress (and stress can be physical, emotional, mental or environmental) our mitochondria adjust how they produce energy and what messages they send around the body. Basically they are actively listening and deciding what is best for us, all the time, despite us being unaware of it.
The messages that they send out ripple through the body, influencing:
Hormones and neuroendocrine function (e.g., cortisol release and thyroid function)
Metabolism (blood sugar regulation, fat storage, insulin sensitivity)
Immunity (inflammatory and anti-inflammatory responses)
Gene expression (epigenetic changes turning on and off different genes which can shape long-term resilience or vulnerability)
In other words, mitochondria translate stress into biological responses that shape how we feel, think, and adapt.
The Stress–Mitochondria Feedback Loop
In a landmark 2015 study, Picard’s team demonstrated that mitochondrial function directly modulates the body’s responses to psychological stress. They showed that:
Stress changes mitochondrial shape, movement, and energy output.
Mitochondria in turn regulate how strongly the brain–endocrine–immune system reacts to stress.
This creates a feedback loop: stress alters mitochondria, and mitochondria determine how the body experiences stress.
When mitochondria are healthy and resilient, the system adapts. But when they are fragile or overloaded, stress tips the balance toward fatigue, inflammation, and illness.
From Fatigue to Mental Disorders: A Shared Energy Problem
This mitochondrial view helps explain why stress-related disorders show up across the spectrum of both body and mind.
Chronic Fatigue Syndrome (ME/CFS)
Patients experience crippling fatigue not relieved by rest and post-exertional crashes.
Research suggests impaired ATP production, oxidative stress, and distress signals from mitochondria such as mitochondrial DNA fragments in circulation.
Stressful events (infection, trauma, psychological strain) are often triggers, consistent with Picard’s idea of failed mitochondrial recalibration after stress.
Depression
Mitochondrial abnormalities have been documented in neurons and immune cells: less ATP, impaired glucose metabolism, and oxidative damage.
Chronic stress drives energy shortfalls and inflammation, both strongly tied to depressive symptoms.
Patients often show fatigue, slowed cognition, and sleep disturbances — all signs of bioenergetic strain.
Depression
Bipolar Disorder
Brain imaging studies reveal unstable energy metabolism in cortical and limbic circuits.
Phosphorous MRS shows abnormalities in high-energy phosphates (ATP, phosphocreatine).
Mitochondrial dysfunction is thought to contribute to the swings between manic overactivation and depressive shutdown.
Schizophrenia
PET imaging consistently finds hypofrontality — reduced glucose metabolism in the prefrontal cortex.
Post-mortem and cellular studies show mitochondrial enzyme and structural deficits.
This “energy drought” in control circuits may underlie cognitive and emotional dysregulation.
My own view is that this might help explain why so many people with Chronic Fatigue Syndrome have other diagnoses like depression or anxiety and vice versa, people with depression have severe fatigue. I have lost count of the number of times that clients I have worked with recount tales of how they simply felt that something was wrong with their energy production, it wasn't simply a case of it 'all being in their mind' but rather that there was some physical link, something wrong with their metabolism. And when people get better they often use energy related anecdotes, like "it was as though a light bulb turned on again".
So evidence is starting to point to the fact that there might be a cross cutting theme, linking these conditions together, a picture emerges: stress taxes mitochondria, impaired mitochondria fail to fuel the brain, and brain energy failure drives symptoms.
Why Do We See Different Symptoms?
This integrative view dissolves the false divide between “mental” and “physical” illness. Chronic fatigue syndrome has often been dismissed as psychological, while depression and schizophrenia have been stigmatised as “not real diseases.” But mitochondrial psychobiology shows that all are deeply biological, rooted in the way our cells generate and manage energy under stress.
1. Where the Energy Deficit Hits (Tissue-Specific Vulnerability)
Mitochondria are distributed unevenly across the body. The brain and muscles are among the most energy-hungry tissues.
If stress-related mitochondrial dysfunction is more pronounced in peripheral tissues (muscles, immune system, autonomic regulation) → symptoms may cluster as chronic fatigue syndrome (low energy output, immune dysregulation, post-exertional malaise).
If dysfunction predominates in neurons, glia, and brain circuits → symptoms manifest as psychiatric illness (impaired neurotransmission, disrupted brain network communication).
The “location” of the bioenergetic shortfall may shape the symptoms and as a result the diagnosis.
2. Thresholds and Compensation
Mitochondria can compensate for stress up to a point. The “energy reserve” varies by person due to:
Genetics (e.g., mitochondrial DNA variants, nuclear-encoded mitochondrial genes)
Developmental programming (prenatal stress, early adversity)
Lifestyle and metabolic health (diet, sleep, toxins, infections)
Someone with more systemic metabolic reserve might only show localized symptoms (e.g., cognitive dysfunction, mood swings), while someone with lower reserves tips into whole-body exhaustion (ME/CFS).
3. Inflammatory Pathways
Mitochondria don’t just make ATP — they also release signals like mtDNA fragments and ROS (reactive oxygen species) that activate the immune system.
In CFS/ME, evidence suggests chronic low-grade immune activation driving fatigue, pain, and malaise.
In psychosis and depression, neuroinflammation is increasingly implicated, where inflammatory cytokines alter neurotransmission and network function.
Which immune pathways are engaged may bias outcomes toward fatigue vs. psychosis or other mental illness.
4. Neurocircuitry Prioritisation
Different psychiatric disorders show characteristic patterns of energy hypometabolism:
Schizophrenia → prefrontal cortex hypometabolism (“hypofrontality”)
Bipolar → limbic–cortical energy instability
Depression → network-specific energy shortfalls + inflammationIf mitochondrial dysfunction interacts with stress in these circuits, psychiatric symptoms emerge; if the brain is spared but muscles/immune system are hit harder, fatigue dominates.
5. The Stress History & Type
Not all stress is the same.
Acute infection or physical trauma may bias toward ME/CFS-type fatigue syndromes.
Chronic psychosocial stress, trauma, or developmental adversity may bias toward psychiatric outcomes.
Sometimes, individuals experience both, especially when systemic energy failure affects multiple organ systems.
These different factors may help explain why one person gets fatigue and another develops psychosis. This is why the bioenergetic model of stress is so powerful: it doesn’t say stress always causes one disease. It explains how stress + mitochondria dysfunction can yield many different outcomes, depending on where the energy system falters. At the moment this remains my personal theory but I think that might be where researchers like Picard are focused in the future.
Supporting Resilience
All of the above does suggest that there are shared strategies that can be used to support resilience which might include:
Protecting circadian rhythms (light exposure, sleep hygiene)
Physical activity within tolerance (to stimulate mitochondrial renewal) and this might be more about pacing in a chronic fatigue situation
Nutritional strategies (including ketogenic diets, where there is growing evidence for serious mental illness)
Stress-reduction practices (breathing, meditation, social connection, spending time in nature)
Other metabolic therapies (such as saunas, supplements and sleep support)
Can the Ketogenic Diet Help?
If stress and mitochondrial dysfunction lie at the root of fatigue and mental illness, then therapies that restore energy metabolism could make a real difference. One of the most promising approaches is the ketogenic diet (KD) — a high-fat, very low-carbohydrate diet that shifts the body’s primary fuel from glucose to ketones.
Why Ketones Support Mitochondria
Ketones (β-hydroxybutyrate, acetoacetate) are not just an alternative fuel — they are mitochondrial enhancers:
Efficient fuel: Ketones generate more ATP per unit oxygen than glucose, improving cellular energy yield.
Redox balance: They reduce oxidative stress and stabilize mitochondrial membranes.
Mitochondrial biogenesis: Ketosis stimulates the creation of new, healthy mitochondria.
Anti-inflammatory effects: Ketones act as signaling molecules that calm overactive immune pathways.
Evidence in Fatigue and Mental Illness
Epilepsy: The ketogenic diet has been used for nearly a century to treat drug-resistant epilepsy, highlighting its stabilizing effects on brain energy.
Chronic fatigue & ME/CFS: Pilot studies suggest ketogenic or low-carb approaches may reduce fatigue, improve mitochondrial efficiency, and stabilize blood sugar and energy supply.
Depression & Bipolar Disorder: Early clinical reports and trials show improvements in mood stability, energy, and cognition. A feasibility study in bipolar disorder (University of Edinburgh, 2023) showed promising effects, with larger randomized trials now underway.
Schizophrenia: Case studies and small trials suggest KD may reduce psychotic symptoms, possibly by normalizing brain hypometabolism and reducing inflammation.
The ketogenic diet doesn’t just suppress symptoms — it targets the root cause: brain energy failure. By providing ketones as a stable, efficient energy source, KD helps mitochondria meet the demands of stress, stabilize neuronal networks, and reduce the metabolic chaos that drives fatigue and psychiatric symptoms.
A New Paradigm: The Bioenergetic Model of Health and Disease
Picard’s research invites us to reframe health itself as an energetic state. Stress is not just a mental strain, but an energetic challenge. Illness, whether physical or psychiatric, it can be understood as a failure of energy regulation at the cellular level.
Mitochondria sit at the center of this story, not only by supplying our energy fuel but as the comman and control centre, sending, processing and communication about our environment to all the tissues of our body, they are how our life experience gets written into our biology. By supporting mitochondrial resilience, using lifestyle practice and metabolic therapies like the ketogeonic diet, we can help restore the energy of both body and mind.
If you want a practical guide to start improving your brain energy then download my FREE Ten Top Tips To Improve Your Brain Energy E-book.
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You can also book a free 30-minute call with me to find out how I can help support you to achieve your health goals.
Disclaimer: Before changing your diet or lifestyle and taking any supplements always seek the advice of your doctor or another suitably qualified professional such as a nutritional therapist. The content of this blog is for informational purposes only and is not a substitute for professional medical advice. Always seek the advice of your doctor with regards to any questions you have about a medical condition.
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