Brain Energy: A Revolutionary Breakthrough in Understanding Mental Health—and Improving Treatment for Anxiety, Depression, OCD, PTSD, and More

by Christopher M. Palmer

Mitochondria are synchronized with our circadian rhythms. Energy production decreases at night to allow for sleep. It increases during the day, so that we can go out into the world to work and play.

sleep-deprived mice had impairment of mitochondrial function in all four brain regions, but especially in the hypothalamus, an area of the brain known to regulate metabolism and many hormones, such as cortisol.

Melatonin, which increases at night and decreases in the morning, has been found to directly stimulate mitophagy.

sleep-deprived mice had higher levels of mitochondrial dysfunction and beta-amyloid accumulation compared to the control group.6 This research helps us understand why and how chronic sleep deprivation is a known risk factor for Alzheimer’s disease.

“Energy metabolism, oxidative stress, and sleep—three processes implicated independently in lifespan, ageing, and degenerative disease—are thus mechanistically connected.”8 What these researchers left out are mental disorders, which are also connected to all of this.

red light tends to stimulate ATP production. However, blue light tends to inhibit ATP production and, instead, increase ROS production.

The different wavelengths affect different proteins on mitochondria. If too much of any spectrum of light is applied, mitochondria can produce too much ROS. This oxidative stress can damage mitochondria themselves and everything else in the cell.

Light exposure on your skin increases a molecule called urocanic acid (UCA) in the bloodstream. UCA travels to the brain where it stimulates neurons that make glutamate. This has a direct impact on learning and memory.13 So, light exposure can help you think better.

Researchers can deliver red and near-infrared light to the scalp and even inside the nose. This treatment is called brain photobiomodulation. These lights increase ATP production, change calcium levels, and stimulate epigenetic signals through direct actions on mitochondria. They are thought to enhance the metabolic capacity of neurons, have anti-inflammatory effects, and stimulate neuroplasticity.14

People with mood disorders can experience fluctuations based on the time of day; this is called diurnal variation.

sleeping pills impair the normal architecture of sleep, which may impact some of the benefits of natural sleep. They can also impair metabolism and mitochondrial function over time, so chronic use can potentially make your problems worse.

Bright-light therapy has been used in a wide variety of disorders, including seasonal affective disorder, bipolar disorder, major depression, postpartum depression, insomnia, traumatic brain injury, and dementia.15 Interestingly, light exposure might even play a role in treating obesity, diabetes, and cardiovascular disease.16 Light therapy can help to regulate your circadian rhythms and normalize your sleep, which, as you now know, can have powerful effects on your metabolism and mitochondria.

To address this, we recommended that he cut out all sweets during the school week. He wasn’t thrilled about this part of the treatment plan but agreed to try it. The second intervention was aimed at better regulating his circadian rhythms and sleep, both of which are known to play a role in bipolar disorder. We used bright-light therapy every morning for at least thirty minutes.

the neural circuits that drive appetite and eating behaviors have also been directly implicated in addiction to tobacco, alcohol, and heroin.

the neural circuits for loneliness overlap directly with the neural circuits that warn of starvation.

chronic social isolation in the fruit fly led to increased eating and decreased sleep.

specific GABA and serotonin neural circuits that were directly involved in obesity and anxiety and depression.3 One neural circuit plays a role in how much you weigh and how you feel.

Some people call this field nutritional psychiatry, one that looks at the role of diet in mental health. Personally, I feel this is too narrow. It’s more than how diet affects brain function. It’s also about how our mental states affect our metabolism, which can impact appetite and feeding behavior, which can affect overall health. It’s a bidirectional relationship. Metabolic affects mental, and mental affects metabolic.

Along with hormonal imbalances, vitamin deficiencies are one of the few examples in psychiatry where there is a clearly identified problem with a simple treatment.

Three of the best-known vitamin deficiencies that can result in mental and neurological symptoms include thiamine, folate, and vitamin B12. These vitamins should be routinely checked in patients with psychiatric and neurological disorders because if they are low, there is a clear treatment for them. What do these vitamins do? They are all required for energy metabolism within mitochondria.

For years, TFAs were ubiquitous in the US food supply. Tragically, it turns out that they are in fact toxic to human health, and they have now been banned in the US. Their use has been associated with increased risk of cardiovascular disease, depression, behavioral aggression, irritability, and Alzheimer’s disease.

Researchers gave pregnant and lactating rats either TFAs or soybean/fish oil with their diets. When the baby rats were born, they got a normal diet without TFAs. At sixty days, the babies from the mothers who got TFAs showed greater anxiety, higher levels of ROS, greater inflammation, and reduced glucocorticoid receptors in the hippocampus.

Let’s look at fiber. As you likely know, fiber is found in fruits, vegetables, and whole grains and is highly recommended these days. Most experts are certain that it plays a beneficial role in metabolic health and aging. Some studies suggest that it also plays a role in mental health.

One of the biggest benefits of fiber is its conversion by microbes in the gut into butyrate, a short-chain fatty acid. Butyrate, in turn, serves as a primary fuel source for the mitochondria in gut cells (colonocytes). It also plays a role in liver cells. One research group found that butyrate directly changes mitochondrial function, efficiency, and dynamics (fusion/fission), and that these changes directly impact insulin resistance, fat accumulation in the liver, and overall metabolism.

insulin resistance is related to mental disorders and mitochondria.

diabetic rats found that high levels of glucose directly impaired mitochondria, as measured by decreased ATP production, increased oxidative stress, and decreased antioxidant capacities, and that all of this likely damages neurons.10

when the cells were stressed, those exposed to high levels of glucose had impaired ability to produce more energy. Again, a paradox. More glucose, or fuel, led to lower levels of ATP.

High glucose led to impairment in processing speed, memory, and attention, and also led to reduced energy levels, increased sadness, and anxiety.

higher levels of blood glucose increased risk for higher levels of amyloid and brain shrinkage.13

mitochondria play a direct role in controlling glucose levels.

Why are those who are obese storing so much fat and/or not burning it?

sometimes, when obese people lose weight, their metabolism plummets. It fights their efforts to lose weight.

Both obesity and mental disorders are associated with mitochondrial dysfunction. When people have both, these conditions can make each other worse.

People with obesity usually have insulin resistance, in both their bodies and brains. One group of researchers specifically looked to see if mitochondrial dysfunction is playing a role, and sure enough, they found signs of mitochondrial impairment in both the brains and livers of insulin-resistant rats.

Insulin resistance takes on a life of its own, though. The pancreas responds to insulin resistance by pumping out more insulin. If a little isn’t working, then send out a lot. That helps! But the problem is that higher levels of insulin usually make insulin resistance even worse over time. They drive hunger and weight gain. And one of the problems with higher and higher levels of insulin is that insulin resistance alone inhibits mitochondrial biogenesis, compounding the metabolic problem.17

helping mitochondria function properly helped the mice deal more effectively with the HFD.

microglial cells were causing brain inflammation in response to the HFD. This occurred before the mice gained any weight.

mitochondrial protein, UCP2, that was driving changes in mitochondrial dynamics (movement, fusion, and fission). When the researchers deleted this protein, the mice no longer had brain inflammation, and shockingly, did not develop obesity even though they continued to have access to the high-fat diet.

for adults, there is now a tremendous amount of science to suggest that eating all the time actually harms health.

Fasting prompts the body to be frugal and encourages autophagy, which has tremendous healing potential. The body hunkers down and makes do with what it has. It’s time to tap those fat stores.

mitochondria are right there to direct things. They immediately change shape. They elongate themselves, fuse with each other, and form long tubular networks.21 What ensues is a spring-cleaning, if you will. The cells identify old and defective proteins and cell parts. They are the first to go in a massive recycling campaign. These proteins and parts are shuttled to lysosomes for degradation. These nutrients are then recycled; some get used for energy, while others might be used for new, essential proteins and cell parts. The cells are looking for anything and everything that is expendable in a carefully orchestrated reboot. So, what about the cells’ mitochondria? Are they also getting destroyed? Well, the defective ones are, as mitophagy also gets activated during this process. But the healthy mitochondria are now working with each other in the long tubular networks. They keep up the pace of ATP production during this process,

Paradoxically, symptoms of hypomania can emerge within the first week or two of starvation. This is likely an adaptive strategy to give the starving person enough energy, motivation, and confidence to get food, no matter what.

Interestingly, it was during the refeeding period that some had the most difficulty. Depression got worse in some of them. Others began binging and purging. Some developed body image concerns. One man cut off three fingers. This study is often used today to understand some of the symptoms of anorexia and bulimia. Starvation itself can cause mental symptoms.

A study of forty women, half with anorexia and the other half without, found mitochondrial dysfunction in the white blood cells of those with anorexia.

Binge eating can make some people feel better because it provides more insulin and glucose to struggling brain cells, and it stimulates the reward centers in the brain. This may be the quickest and easiest way to overcome insulin resistance—eat a lot of sugar. Unfortunately, as I just discussed, this makes matter worse over time. For others, restricting eating can improve mood because it can provide stress hormones or ketones (you’ll hear more about these soon) that can be helpful to struggling brain cells. These two extremes of overeating and undereating can both produce rewarding experiences in different people.

explains why people with all mental disorders are more likely to develop an eating disorder. They are looking for ways to feel better.

researchers found that the microbiome in obese mice extracts more nutrients and calories from food than in thin mice. When this obese microbiome is transferred to thin mice, the thin mice gain weight.

Animal models and small human trials have shown that the gut microbiome appears to play a role in depression, anxiety, autism, schizophrenia, bipolar disorder, and eating disorders. There is also evidence for the role of the gut microbiome in epilepsy and neurodegenerative disorders.

Gut bacteria get first dibs on all the food we eat. They produce a variety of metabolites, neurotransmitters, and hormones that they secrete into our guts. These get absorbed into our bloodstream and can affect our metabolism and brain function. A second way that signals get sent from the gut to the brain is through hormones and neuropeptides that are produced in the cells that line the intestinal tract. These, too, are known to travel throughout the body, including to the brain, and have widespread effects on metabolism and brain function. Finally, the gut has an intricate nervous system unto itself that communicates directly with the brain and vice versa.

excessive use of vitamins and supplements can actually cause metabolic problems. Healthy metabolism is about balance—not too much and not too little.