5 questions: Shebani Sethi on the link between metabolism and mental health

5 questions: Shebani Sethi on the link between metabolism and mental health

Recent data from the Centers for Disease Control and Prevention reveals that more than 40% of American adults are classified as obese and 36% report symptoms of anxiety, depression or both. According to Shebani Sethi, MD, assistant clinical professor of psychiatry and behavioral sciences, the two epidemics are closely linked.

Board-certified in psychiatry and obesity medicine, Sethi is the founder of Stanford Medicine’s Metabolic Psychiatry Clinic, the first academic clinic focused on treating patients with both mental illnesses and metabolic disorders – conditions such as insulin resistance or prediabetes, high cholesterol, hypertension, and overweight or obesity.

Sethi coined the term “metabolic psychiatry” in 2015 after seeing a high prevalence of metabolic disorders in her treatment-resistant psychiatric patients and realizing that to provide proper psychiatric care she needed to treat both issues simultaneously.

She told us how metabolic disorders affect the brain and how treating mental illness through nutrition can offer patients new hope.

1. How do you define metabolic psychiatry?

Metabolic Psychiatry is a new subspecialty focused on targeting and treating metabolic dysfunction to improve mental health outcomes. A growing body of evidence points to a link between mental illness and impaired metabolism in the brain; thus, treatment addressing this dysfunction may improve patient outcomes.

Rates of metabolic disorders are already very high in the general population. One study found that up to 88% of American adults have poor metabolic health, and in people with psychiatric illnesses the rates are higher. In fact, research by colleagues at Stanford Medicine suggests that developing a metabolic disorder such as insulin resistance can double your risk of depression, even if you have no history of mental illness.

The good news is that in our clinic, we have seen encouraging improvements in mental health after treating metabolic conditions through non-pharmacological methods (including diet and lifestyle changes) in combination with medication. Research shows that people with treatment-resistant bipolar disorder do better when insulin resistance is treated.

For a long time, doctors viewed nutrition as a secondary therapy, an adjunct to drugs that might lower blood pressure or improve diabetes. But we realized that nutritional metabolic therapy can serve as an important medical intervention for mental illness, one that can alter brain structure and function. We are taking lessons from our colleagues in neurology who over a century ago recognized the links between metabolism in the brain and body, which led to the successful treatment of pediatric epilepsy with ketogenic diets before the advent of the first anti-epileptic drug.

2. It’s easy to see how mental illness can lead to conditions such as obesity or diabetes, because someone who suffers from a mental disorder may be unable to eat well or exercise. But you say the reverse is also true. How it works?

We don’t know all the mechanisms, but we do know that patients who are diagnosed with first-episode schizophrenia – even before being treated with medication – have already disrupted insulin and glucose metabolism in the brain. .

As insulin resistance develops, the brain becomes “more permeable”, meaning more substances can cross the blood-brain barrier and enter brain tissue. This results in a buildup of toxic substances and increased inflammation. We see much more inflammation in the brains of people with mental illness, especially in treatment-resistant patients, than in healthy people.

There has also been a lot of research over the past century regarding metabolism and mitochondrial dysfunction, and how it affects brain activity in mental illness. Mitochondria are the seat of energy production and consumption in the cell. If they aren’t working properly, communication and connections between brain cells – also called neural networks – are less stable, impairing cognition and worsening mental health.

We are investigating whether a change in diet, including a ketogenic diet, can improve this brain instability. In collaboration with fellow UC San Francisco neuroscientist Judith Ford, we are recruiting patients who have been diagnosed with bipolar disorder or schizophrenia in a randomized controlled trial exploring the effects of a ketogenic diet on drug resistance. insulin and neural network stability as measured by functional MRI.

3. Can you tell us more about the ketogenic diet and why it might benefit some patients with severe mental illness?

I want to emphasize that a ketogenic diet is not for everyone. It really should be called a therapy rather than a diet, as it is a metabolic intervention meant to be undertaken under medical supervision.

That said, a ketogenic diet is a very low-carb, high-fat diet with a moderate protein intake. Patients on this diet avoid bread, rice, pasta, and cereals, while consuming whole foods like eggs, avocado, nuts, fish, and chicken. Vegetarians can also follow a ketogenic diet, but food options may be limited.

Carbohydrate restriction forces the body to burn fat for energy and causes the liver to make compounds called ketones, which can be used to fuel brain cells instead of glucose. In our clinic, we try to support patients in what we call “nutritional ketosis”, which means that their body receives all the nutrition it needs while maintaining blood levels of ketones between 0.5 and 5 millimolars. (This is quite different from ketoacidosis, a dangerous condition of 50 or more millimolar ketones.)

Although ketogenic diets sometimes get a bad rap, lumped in with fad diets that can be dangerous or difficult to maintain, ketogenic diets have been used for decades to treat pediatric epilepsy and other neurodegenerative conditions. A lot of research shows that ketogenic diets increase mitochondrial growth and reduce inflammation and oxidative stress in the brain, but so far no one has studied the effect of a ketogenic diet specifically on mental illness. .

4. You recently completed a pilot study of patients with severe mental illness who tried the ketogenic diet for four months. Can you describe some of your preliminary results?

In this pilot study, we taught 22 patients with severe bipolar disorder or schizophrenia how to maintain a ketogenic diet. It was all in the real world, meaning we weren’t controlling food intake in a temporary inpatient setting, and we weren’t delivering meals, but teaching patients how to buy and prepare their own food. Despite the severity of their mental illness, our patients have successfully embraced the ketogenic diet as a lifestyle change. However, there is a selection bias, as those who entered the study may have been a more motivated population.

After four months, our preliminary results were very encouraging: they included a 30% reduction in central abdominal fat, an 11% drop in BMI, and a 17% drop in heart inflammation, measured by a marker called high-sensitivity C-reactive protein. . Perhaps most importantly, we saw a 30% improvement in our patients’ Global Clinical Impressions Inventory, which is the gold standard psychiatric assessment we use to assess symptoms of mental illness. Additionally, we saw improvements in sleep.

We are analyzing the rest of the data and will present our findings at the International Society for Bipolar Disorders conference next June. Additionally, we are recruiting patients for randomized controlled trials to compare a ketogenic diet with diets based on USDA Standard Dietary Guidelines. It’s one step at a time, but if we’re able to change the structure and function of the brain through non-pharmacological methods like diet, that’s a very positive step forward for chronic mental illness.

5. Can you give an example of a patient who could be treated in your clinic? How does your approach differ from treating just their mental illness or just treating their metabolic disorder?

I treat patients who either have a psychiatric condition alone or a psychiatric condition as well as a metabolic problem, including patients with eating disorders. After doing a physical exam, taking a complete medical and psychiatric history, and reviewing metabolic biomarkers, I assess the patient’s dietary habits and medications to see what metabolic interventions might be appropriate.

I rely heavily on non-pharmacological interventions and do a lot of nutrition counseling, which I find very satisfying. Often my patients have misconceptions about what’s healthy and what’s not, so I start from scratch and teach them “Nutrition 101,” taking a science-based approach. I also assess whether certain types of therapy or medication might be helpful: are they emotional eaters or not?

Although drugs can save lives, some psychiatric drugs can contribute to metabolic dysfunction. So I work with my patients’ other doctors to adjust their medications when possible, avoiding medications that cause weight gain or insulin resistance. After all, in our Hippocratic Oath, we pledge to use all available measures for the benefit of our patients, including diets.

More resources and information on how to enroll in ongoing clinical trials can be found at Stanford Medicine’s Metabolic Psychiatry community page.

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