The Cellular Link Between Mental Illness and Metabolic Disease
At age 33, Tom had spent most of his adult life struggling with schizoaffective disorder. He experienced daily hallucinations and delusions and was plagued by anxiety and depression.
Medications helped him control some of his symptoms, but they also caused him to gain weight. Heavy to begin with, he put on more than 100 pounds. He didn’t want to see another doctor, and so he asked his psychiatrist for help. They tried several diets without success before they gave the ketogenic diet a shot.
Within a few weeks, Tom had begun to lose weight. To his doctor’s surprise, his psychiatric symptoms also mellowed. After two months on the diet, these changes were even more dramatic. Eventually Tom lost more than 150 pounds, and his mental state improved to the point that he could move out of his father’s house and live on his own.
“I was flabbergasted,” recalls his psychiatrist, Christopher Palmer. “This man had a psychotic disorder that had resisted more than a decade of treatment.
Nothing in my knowledge or experience suggested that the ketogenic diet would treat his symptoms.”
‘Once you do a deep dive into the science of mitochondria, you can connect the dots to what causes mental illness.’
Palmer, MD, is a neuroscientist and assistant professor of psychiatry at Harvard Medical School. In his new book Brain Energy, he tells Tom’s story and describes how that clinical experience led him to explore the connection between metabolic dysfunction and mental disorder.
“This is not a book about weight loss or the ketogenic diet,” he says. Rather, it’s an exploration of the underlying cellular and metabolic mechanisms that could explain how the ketogenic diet was able to help a person like Tom find relief from his psychiatric symptoms. This exploration has helped Palmer develop what he calls a novel theory for mental illness
“The overall theme of the book is that mental disorders are metabolic disorders of the brain,” he says. “When you take an overarching view of metabolism and ask basic questions like what is a metabolic abnormality at a cellular level, you are led to mitochondria, and once you
do a deep dive into the science of mitochondria, you can connect the dots to what causes mental illness.”
It’s difficult to look objectively at the state of public health in the United States and see anything other than an ongoing crisis.
While it’s possible to be large and healthy (or slim and sick), most people who are obese are suffering from what the CDC describes as a “costly chronic disease.”
That disease is more common now than ever before. Between 1999–2000 and 2017–2020, the rate of obesity in the U.S. jumped from 31% to 42%. Rates of severe obesity approximately doubled from 4.7% to 9.2%. That’s according to figures from the National Center for Health Statistics.
Adipose (fat) tissue produces hormones that regulate metabolism. Excess fat and the overproduction of these hormones can cause or contribute to a range of metabolic complications that includes Type 2 diabetes, hypertension, and premature heart disease, which are also all increasingly commonplace.
Likewise, the line graphs charting mental health in the U.S. are all sloped in the wrong direction. Nearly one in
five Americans today is living with a mental illness, according to the National Institutes of Mental Health. Depression, anxiety, schizophrenia, bipolar disorder, and autism are all more common now than they used to be.
Energy shortfalls caused by mitochondrial dysfunction cause the brain to fail in predictable ways, and psychiatric symptoms or disorders are the result.
Traditionally, mental and psychiatric conditions have been treated as distinct from disorders of the body. But Palmer argues this is wrong. He points out what is an established fact: that people with obesity, diabetes, and other metabolic conditions are much, much more likely to develop mental illnesses such as depression, anxiety, and bipolar disorder.
“It is not a coincidence that as rates of obesity and diabetes have skyrocketed, the rates of mental disorders have also skyrocketed,” he says. “They are interrelated because they are all metabolic disorders.”
Specifically, he says the health of mitochondria — the so-called powerhouses of cells — are “the common pathway” that link mental and metabolic disorders.
Mitochondria produce the energy that powers cellular activity (hence the “powerhouse” nickname). But they do much, much more than that: they help to regulate metabolism; they help produce and regulate neurotransmitters; they help coordinate immune system functioning; they help manage stress; and they play a major role in gene expression. “When mitochondria don’t function properly, the human body doesn’t function properly,” Palmer says.
This is accepted science in the field of metabolic disease, but it has garnered less attention in the field of psychiatry despite a solid foundation of evidence. “We have literature dating back to the 1940s showing that metabolic and mitochondrial abnormalities are present in the brains and bodies of people with mental illness,” he says. “The studies have been done and the data is there. The mind and body are connected, and the metabolic theory of mental illness can explain this connection down to the cellular level.”
On the role of mitochondria in mental illness, Palmer says he supports a theory that others before him have proposed: that energy shortfalls caused by mitochondrial dysfunction can cause the brain to “fail” in predictable ways, and that psychiatric symptoms or disorders are the result of these failures.
What causes the type of mitochondrial dysfunction that could promote both metabolic disease and mental illness?
Palmer says the list is long, and contains most of the usual suspects. He mentions stress, lack of sleep, a poor diet, too little exercise, and environmental toxins as some of the established drivers of mitochondrial impairment. A person may also inherit from their parents a genetic or epigenetic predisposition to mitochondrial dysfunction.
“There are so many things in modern lifestyles that contribute to this,” he says. “The human species has a serious problem, and when it comes to metabolic disease, our simplistic view that these are all problems of willpower — of not eating right or not getting enough exercise — is just failing miserably.”
‘We can better regulate environmental toxins that we know contribute to metabolic dysfunction, rather than just telling people these disorders are caused by eating too much or failures of willpower.’
What are the solutions? Returning to the ketogenic diet, he says it does several things that may have helped his
patient Tom, and that may be instructive to those who treat mental illness.
“It has effects on neurotransmitters and on hormone levels. It decreases brain inflammation and it changes the gut microbiome. We know this from decades of research on ketogenic diets for the treatment of seizures,” he says. “But most importantly for my thesis, it results in two processes that relate to mitochondria.” First of all, it promotes a mitochondrial repair process called mitophagy, he says. It also stimulates the production (biogenesis) of mitochondria in cells.
The ketogenic diet isn’t the only intervention that can effect these benefits. “Intermittent fasting and fasting-mimicking diets do this,” he says. “Proper sleep and exercise and stress reduction increase mitochondrial health and resiliency.”
He also highlights peer-reviewed research on mindfulness, yoga, and other relaxation practices. “Work done by a Harvard group found that these practices directly control expression of genes related to mitochondria, and to metabolism more broadly,” he says. One 2013 study from that group concluded that the body’s relaxation response “may evoke its downstream health benefits by improving mitochondrial energy
production and utilization and thus promoting mitochondrial resiliency.”
Notably, Palmer does not single out psychiatric medications as particularly helpful. He says that, yes, these drugs can provide symptom relief for some people. But he also acknowledges a truth that most
experienced members of his profession must know (though few are willing to state publicly): that the drugs commonly used to treat mental illnesses, such as antidepressants, tend not to provide a durable benefit for those who take them, and in some cases do more harm than good.
A lot of the problems and fixes he discusses are familiar. The idea that stress-reduction, proper sleep, exercise, and healthy eating patterns can heal the mind and body is conventional. But establishing an underlying biological mechanism that explains the connection between physical and mental illness could help us do more to limit environmental factors that contribute to these dysfunctions. “For example, we can better regulate environmental toxins that we know contribute to metabolic dysfunction, rather than just telling people these disorders are caused by eating too much or failures of willpower,” he says.
“We have a mounting crisis in the mental health field and also in the metabolic health field,” he adds. “What we’re doing now isn’t working. We need to better understand the science and use it to develop treatment strategies that address both of those at same time.”
https://medium.com/@mheidj/the-cellular-link-between-mental-illness-and-metabolic-disease-a63a817af801
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