From Chemical Imbalance to Metabolic Breakthrough: A New Path for Mental Health

Mark Hyman

Sep 15, 2025

Episode description

Many psychiatric labels—like bipolar disorder and schizophrenia—can obscure underlying biology, and symptom checklists often fail to explain or heal what’s really going on. Emerging evidence reframes mental illness as a problem of brain energy, mitochondria, and inflammation—shaped by insulin signaling, circadian rhythm disruption, the gut–brain axis, toxins, infections, and nutrient status. Metabolic interventions such as ketogenic nutrition, already established for epilepsy, show promise for rebalancing neurotransmitters, lowering neuroinflammation, and improving overall brain function. With depression now a leading cause of disability, shifting from “manage the symptoms” to “fix the biology” could dramatically improve outcomes where standard drugs fall short.

In this episode, Dr. Christopher Palmer, Dr. Todd LePine, Dr. Iain Campbell and I explore how rethinking mental illness as a metabolic and inflammatory disorder of the brain—rather than just a chemical imbalance—could transform the treatment and prevention of conditions like depression, bipolar disorder, and schizophrenia.

Dr. Chris Palmer is a psychiatrist and researcher working at the interface of metabolism and mental health. He is the Director of the Department of Postgraduate and Continuing Education at McLean Hospital and an Assistant Professor of Psychiatry at Harvard Medical School. For over 25 years, he has held leadership roles in psychiatric education, conducted research, and worked with people who have treatment-resistant mental illnesses. He has been pioneering the use of the medical ketogenic diet in the treatment of psychiatric disorders - conducting research in this area, treating patients, writing, and speaking around the world on this topic. More broadly, he is interested in the roles of metabolism and metabolic interventions on brain health.

Dr. Todd LePine graduated from Dartmouth Medical School and is Board Certified in Internal Medicine, specializing in Integrative Functional Medicine. He is an Institute for Functional Medicine Certified Practitioner. Prior to joining The UltraWellness Center, he worked as a physician at Canyon Ranch in Lenox, MA, for 10 years. Dr. LePine’s focus at The UltraWellness Center is to help his patients achieve optimal health and vitality by restoring the natural balance to both the mind and the body. His areas of interest include optimal aging, bio-detoxification, functional gastrointestinal health, systemic inflammation, autoimmune disorders, and the neurobiology of mood and cognitive disorders. 

Dr. lain Campbell is the first academic research fellow to specialise in Metabolic Psychiatry as the Baszucki Research Fellow in Metabolic Psychiatry at the University of Edinburgh. He has a PhD in Global Health from the University of Edinburgh and is a principal investigator on a pilot trial of a ketogenic diet for bipolar disorder. He is a workstream lead and co-investigator on the first publicly funded research

Episode description

Many psychiatric labels—like bipolar disorder and schizophrenia—can obscure underlying biology, and symptom checklists often fail to explain or heal what’s really going on. Emerging evidence reframes mental illness as a problem of brain energy, mitochondria, and inflammation—shaped by insulin signaling, circadian rhythm disruption, the gut–brain axis, toxins, infections, and nutrient status. Metabolic interventions such as ketogenic nutrition, already established for epilepsy, show promise for rebalancing neurotransmitters, lowering neuroinflammation, and improving overall brain function. With depression now a leading cause of disability, shifting from “manage the symptoms” to “fix the biology” could dramatically improve outcomes where standard drugs fall short.

In this episode, Dr. Christopher Palmer, Dr. Todd LePine, Dr. Iain Campbell and I explore how rethinking mental illness as a metabolic and inflammatory disorder of the brain—rather than just a chemical imbalance—could transform the treatment and prevention of conditions like depression, bipolar disorder, and schizophrenia.

Dr. Chris Palmer is a psychiatrist and researcher working at the interface of metabolism and mental health. He is the Director of the Department of Postgraduate and Continuing Education at McLean Hospital and an Assistant Professor of Psychiatry at Harvard Medical School. For over 25 years, he has held leadership roles in psychiatric education, conducted research, and worked with people who have treatment-resistant mental illnesses. He has been pioneering the use of the medical ketogenic diet in the treatment of psychiatric disorders - conducting research in this area, treating patients, writing, and speaking around the world on this topic. More broadly, he is interested in the roles of metabolism and metabolic interventions on brain health.

Dr. Todd LePine graduated from Dartmouth Medical School and is Board Certified in Internal Medicine, specializing in Integrative Functional Medicine. He is an Institute for Functional Medicine Certified Practitioner. Prior to joining The UltraWellness Center, he worked as a physician at Canyon Ranch in Lenox, MA, for 10 years. Dr. LePine’s focus at The UltraWellness Center is to help his patients achieve optimal health and vitality by restoring the natural balance to both the mind and the body. His areas of interest include optimal aging, bio-detoxification, functional gastrointestinal health, systemic inflammation, autoimmune disorders, and the neurobiology of mood and cognitive disorders. 

Dr. lain Campbell is the first academic research fellow to specialise in Metabolic Psychiatry as the Baszucki Research Fellow in Metabolic Psychiatry at the University of Edinburgh. He has a PhD in Global Health from the University of Edinburgh and is a principal investigator on a pilot trial of a ketogenic diet for bipolar disorder. He is a workstream lead and co-investigator on the first publicly funded research

Mindsip insights from this episode:

Reframe mental illness as metabolic disorder of the brain

Mental disorders can be viewed as metabolic disorders of the brain, stemming from mitochondrial dysfunction rather than just being a chemical imbalance.

Understand glial cells' role in brain immunity and mental health

About 90% of the brain consists of glial cells, not neurons, and these cells form the brain's immune system, which drives neuroinflammation in many mental disorders.

Recognize mitochondria as key regulators of hormones and inflammation

Mitochondria are not just powerhouses; they are primary regulators of key hormones like cortisol and testosterone and are central to inflammation and neurotransmitter function.

Implement ketogenic diet to reverse severe psychosis

A ketogenic diet, initially used for weight loss, led to the full remission of a patient's schizoaffective disorder, resolving hallucinations and delusions that were resistant to standard medications.

Test for NMDA receptor antibodies to identify psychosis-related inflammation

Anyone who has a psychotic break should get an NMDA receptor antibody test to see if neuroinflammation is the driving cause of their symptoms.

Reconsider schizophrenia as an immune disorder through bone marrow insights

Case reports show schizophrenia can be 'transplanted' via bone marrow, suggesting it may be an immune disorder rather than a primary brain disease.

Reassess bipolar disorder as an evolutionary mismatch

Bipolar disorder may be an evolutionary mismatch where ancient mechanisms for seasonal energy regulation are dysregulated by modern factors like artificial light and diet.

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