Shebani Sethi talks about a moment that altered the course of her career. She was treating patients with psychiatric conditions that were resistant to treatment, such as schizophrenia, bipolar disorder, or depression, and she kept observing the same thing. They had metabolic issues as well. resistance to insulin. pre-diabetes. high cholesterol. obesity. This overlap continued to occur so frequently that it started to resemble a message the data was attempting to convey rather than a coincidence. Sethi first used the term “metabolic psychiatry” in 2015 to describe what she was starting to do. By that time, she was at Stanford, where she was constructing the world’s first academic clinic devoted to treating patients with metabolic disorders and mental illness at the same time.
Metabolic Psychiatry: Key Facts & Reference
| Field | Details |
|---|---|
| Field Name | Metabolic Psychiatry |
| Term Coined By | Dr. Shebani Sethi, MD — 2015 |
| Dr. Sethi’s Role | Clinical Assistant Professor, Psychiatry & Behavioral Sciences; Founder, Stanford Medicine Metabolic Psychiatry Clinic |
| Stanford Clinic | First academic metabolic psychiatry clinic in the world |
| Certifications (Sethi) | Board-certified in both psychiatry and obesity medicine |
| Core Concept | Mental illnesses may be rooted in metabolic dysfunction impacting brain energy production |
| Key Mechanism | Insulin resistance → cerebral glucose hypometabolism → mitochondrial dysfunction → neuroinflammation → psychiatric symptoms |
| Bidirectional Link | Poor metabolic health doubles risk of depression; mental illness increases metabolic disorder risk |
| % American Adults with Poor Metabolic Health | Up to 88% (cited research) |
| Stanford Pilot Study | 22–26 participants with bipolar disorder/schizophrenia; 4-month ketogenic diet |
| Stanford Pilot Results | 30% reduction in central abdominal fat; 11% BMI drop; 17% drop in cardiac inflammation; 30% improvement in psychiatric symptoms |
| Ketogenic Therapy History | Used for over 100 years to treat drug-resistant epilepsy in children |
| Key Book | “Brain Energy” by Dr. Christopher Palmer, Harvard psychiatrist |
| Metabolic Mind | Organization founded by Baszucki Foundation; supports metabolic psychiatry research globally |
| Active Clinical Trials | 75+ worldwide across bipolar disorder, schizophrenia, depression, PTSD, Alzheimer’s, autism, and more |
| FDA-Relevant Note | Ketogenic therapy is a medical intervention requiring clinical supervision, not a consumer diet |
| Bret Scher, MD | Medical Director, Baszucki Group & Metabolic Mind; co-authored key field summaries |
| Key Reference — Stanford Medicine | 5 Questions: Shebani Sethi on metabolism and mental health — Stanford Medicine |
| Key Reference — Metabolic Mind | What is Metabolic Psychiatry? — Metabolic Mind |
The traditional understanding of mental illness has always operated from the inside out, viewing it as a neurotransmitter, chemical imbalance, and psychological experience issue that required medication and treatment. Millions of people have benefited from that framework. Millions of others have also been left behind. These are not edge cases, such as cases of schizophrenia where antipsychotics control symptoms but never produce true remission, treatment-resistant depression, and bipolar disorder that alternates between medications without finding stability. They are prevalent, and the conventional model has had difficulty explaining them. An alternative explanation is provided by metabolic psychiatry. It raises the question of whether the energy production system that initially enables neurotransmitter function is the issue rather than the neurotransmitters themselves.
Insulin is the first component of the mechanism. The brain’s main energy source is glucose, but insulin makes it possible for brain cells to use glucose effectively. The brain enters what researchers refer to as a state of cerebral glucose hypometabolism when insulin resistance develops, as it does in a sizable and increasing percentage of the population, frequently long before blood sugar levels become obviously abnormal. The blood contains a lot of glucose. The brain might even contain a lot of glucose. However, the brain cells cannot properly metabolize insulin in the absence of functional insulin signaling. They don’t have enough energy. The cellular components that produce that energy, called mitochondria, start to malfunction. The level of inflammation rises. The delicate balance of neurotransmitters, especially the inhibitory GABA and the excitatory glutamate, leans toward oxidative damage and chronic overstimulation. The neurological environment that results in depression, mood instability, psychosis, and cognitive impairment is the outcome, according to the metabolic psychiatry framework.
Insulin resistance can double the risk of depression, even in those without a history of mental illness, according to Stanford research. Additionally, research indicates that individuals with a first episode of schizophrenia already exhibit abnormal insulin and glucose metabolism in their brains prior to receiving any medication. This is significant because it casts doubt on the notion that metabolic issues in mental health patients are merely a result of sedentary lifestyles, unhealthy diets, or the drugs themselves. In at least some of these cases, the psychiatric diagnosis seems to come after the metabolic dysfunction. One of the reasons metabolic psychiatry is attracting genuine scientific interest rather than merely clinical curiosity is this reversal of expected causality.
The main therapeutic intervention is ketogenic therapy, which is a well-designed, medically supervised dietary strategy that causes the brain to switch from using glucose as a fuel source to using ketones. This is not the consumer-grade keto trend. Even when insulin signaling is compromised, the brain can effectively use ketones, avoiding the metabolic bottleneck that might be causing symptoms. For over a century, children with drug-resistant epilepsy have been treated with the ketogenic diet, which stabilizes neuronal excitability through metabolic means. Looking at that century of neurological data, psychiatry, which broke away from neurology as a separate field decades ago, is wondering why it took so long to apply the same logic to disorders like schizophrenia and bipolar disorder.
In Sethi’s Stanford pilot study, 22 to 26 patients with severe bipolar disorder or schizophrenia were enrolled, and they were required to follow a ketogenic diet for four months as a real-world intervention. There were no controlled meals or inpatient settings, just instruction on how to purchase and prepare food. A 30 percent decrease in central abdominal fat, an 11 percent decrease in BMI, a 17 percent decrease in cardiac inflammation as determined by high-sensitivity C-reactive protein, and a 30 percent improvement in psychiatric symptoms as determined by the gold-standard clinical global impression scale were the startling preliminary results. Bipolar disorder, schizophrenia, depression, PTSD, and other conditions are currently the subject of more than 75 ongoing international randomized controlled trials.
Observing this field’s growth gives me the impression that medicine’s understanding of the connection between the body and the mind is changing conceptually. It’s difficult to ignore the implications of framing “mental illness as brain energy dysfunction” that go far beyond the ketogenic diet. It raises issues with sleep, exercise, circadian rhythm, processed food consumption, and the drugs that psychiatry has traditionally prescribed without fully considering their metabolic effects. Certain antipsychotics and antidepressants exacerbate insulin resistance. Reviewing and modifying drugs that might be unintentionally exacerbating the metabolic dysfunction they were prescribed with is a part of Sethi’s clinical practice.
All of this is not proven science. The field is still in its infancy, there aren’t many trials, and it’s still unclear who benefits the most and why. However, significant academic institutions, professional training programs, and research funding organizations are taking it seriously because of the initial results. There was only one metabolic psychiatry clinic worldwide five years ago. These days, the field’s infrastructure—clinics, CME programs, clinical trials, and patient communities—is being constructed in real time.
