Chapter 14

CONTRIBUTING CAUSE

Sleep, Light, and Circadian Rhythms

Sleep, light, and circadian rhythms are all interconnected. They play a powerful role in metabolism, mitochondrial function, metabolic disorders, and mental disorders. Although the biology of these topics is complex, I’ll offer a high-level overview and a sample of the evidence to demonstrate that these contributing causes all play a role in the theory of brain energy.

When we sleep at night, our bodies and brains enter a “rest and repair” state. The overall metabolic rate and temperature of the body decline while cells perform maintenance functions and make needed repairs vital to both short-term and long-term health. The brain undergoes many changes in neurons that are thought to play a role in learning and memory consolidation. Without sleep, cells can fall into a state of disrepair and begin to malfunction.

Sleep is part of the body’s overall metabolic strategy. It is guided by circadian rhythms. The body has “clocks,” both in the brain and in virtually all cells, that govern many biological processes. In the end, they all relate to metabolism. An area of the hypothalamus called the suprachiasmatic nucleus (SCN) plays a key role. The SCN detects light from our eyes and generates hormonal and nervous system responses. These signals, in turn, influence the peripheral clocks in all the cells of the body by turning thousands of genes throughout the body on or off. The circadian rhythm is largely driven by two things—light and food. It gets synchronized to cycles of light or dark and feeding or fasting.

An optimal amount of sleep for adults is about seven to nine hours per night but varies among people. Age, activity level, and other factors play a role. Infants and children need more sleep as their bodies are growing. The elderly require less sleep. When people are ill, they need more sleep temporarily, as sleep helps conserve energy. Sleep allows metabolic resources to be devoted to growth, maintenance, and repair functions.

When a person’s safety is threatened, sleep needs to wait. Rest and repair are never as important as survival. This includes not just physical survival but also status in society. Anything that has us worried, including most psychological and social stressors, can disrupt sleep. This is normal, not a disorder.

Sleep problems can be defined as too much, too little, or poor-quality sleep. Any of them can take a metabolic toll. Problems sleeping can exacerbate all mental and metabolic disorders. Sleep deprivation can worsen depression, mania, anxiety, dementia, ADHD, schizophrenia, and substance use disorders. It can also exacerbate metabolic disorders. People with diabetes can see their blood sugars rise. People with obesity can gain more weight. People who have already had a heart attack can have another one. These are all examples of sleep problems worsening existing disorders. However, they can also be contributing causes to the onset of such disorders. There have been many studies of normal, healthy people being sleep deprived. If the sleep deprivation is extreme, it can result in depression, anxiety, cognitive impairment, mania, and psychosis. Genetic studies have found an association between the clock genes and autism, bipolar disorder, schizophrenia, depression, anxiety, and substance use disorders.¹ Long-term studies looking at people who don’t get enough sleep have found that they are more likely to develop all the metabolic disorders as well. It can lead to and exacerbate epilepsy and Alzheimer’s disease, too.

Sleep is in a feedback cycle with mental and metabolic disorders. These disorders themselves can cause sleep problems, which can then make the disorders even worse. It’s well described that sleep problems are a common symptom of most mental disorders. What’s less well known is that sleep problems are also more common in people with obesity, diabetes, cardiovascular disease, Alzheimer’s disease, and epilepsy.

There are many different types of sleep disorders, including obstructive sleep apnea, when people have obstructed airways at night and stop breathing, and restless legs syndrome, when people can’t stop moving their legs at night. The most common sleep disorder, however, is plain old insomnia.

So, we see strong bidirectional relationships between sleep, mental, and metabolic disorders. Clearly, something is going on here. We know that sleep problems result in a stress response and increase levels of inflammation. I’ve already discussed how those can impact mental and metabolic disorders. But there’s more to the story once again. We have several lines of evidence demonstrating a feedback cycle between mitochondria, sleep, and circadian rhythms.

Sleep and Circadian Rhythms Impact Mitochondrial Function

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.

Researchers have identified a specific protein, DRP1, that plays a central role in mitochondrial fission and ATP production.² The circadian clock controls this protein, which then synchronizes mitochondrial function with our daily rhythm. Interestingly, DRP1 is necessary for feedback to the circadian clock, suggesting that mitochondria may be influencing the clocks themselves through this feedback mechanism.

Another study looked at mice and the effects of sleep deprivation on mitochondrial function in four different brain regions. They found that 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.³

Hormones play a role in sleep and mitochondrial function as well. Abnormal levels of cortisol through the night can be caused by sleep problems. Cortisol levels can then impact brain function and cognitive impairment.⁴ Melatonin, which increases at night and decreases in the morning, has been found to directly stimulate mitophagy. The lack of melatonin-induced mitophagy has been tied to cognitive deficits in mice.⁵ This research suggests that poor sleep leads to mitochondrial dysfunction, which then leads to cognitive impairment, which can then lead to Alzheimer’s disease. This hypothesis was further supported by another research group that deprived mice of sleep for nine months and then looked at mitochondrial function and the accumulation of beta-amyloid. Sure enough, the 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.

One more example—remember NAD? This metabolic coenzyme is controlled by circadian clocks and directly influences mitochondrial activity, resulting in more ATP production.⁷ So, when your circadian rhythm is off, your production of NAD will be off, which will throw off your mitochondrial function and your mental and metabolic health.

Mitochondria Play a Role in Controlling Sleep

The regulation of sleep involves numerous neurons and neurotransmitters, and many aspects are still being worked out. By no means is this a simple topic.

However, recent research does implicate at least one direct role for mitochondria. A 2019 Nature article looked at neurons that are known to induce sleep in the fruit fly to determine what makes them turn on and off. In other words, what makes these flies fall asleep? The researchers found that it’s mitochondria. The levels of ROS in mitochondria were linked directly to specific receptors that induce sleep. The researchers summarized the importance of this finding: “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.

Another group of researchers looked at fruit flies with mitochondrial defects and found that they, too, had disrupted circadian rhythms and sleep patterns, further implicating mitochondria as crucial players.⁹ A study in humans with mitochondrial defects found that almost 50 percent had sleep-disordered breathing problems.¹⁰

Light Impacts Mitochondria and the Brain

Light stimulates mitochondria, and different wavelengths of light have different effects. For example, red light tends to stimulate ATP production. However, blue light tends to inhibit ATP production and, instead, increase ROS production.¹¹ 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.

The clearest example of “too much” light is in skin cells. When people lay out in the sun, the photons of light stimulate mitochondria in their skin. When exposure is excessive, it can lead to premature aging of the skin (moles and wrinkles) or even skin cancer.¹² Mitochondria are thought to play an important role in all of this.

Light exposure also affects the brain. There are at least three ways this occurs:

The Effect of Sleep, Light, and Circadian Rhythms on Symptoms

There are countless ways that modern humans mess up sleep. We take our phones to bed with us. We read in bed—with a light, of course. We wake up in the middle of the night and turn on our computers and televisions. We stay up late gaming or binge-watching Netflix. We work night shifts. We stay out all night and party. We pull all-nighters to finish important projects due the next day. We travel far distances and get jet-lagged. All these behaviors impact our circadian rhythms and sleep, taking a metabolic toll.

Others can’t sleep, no matter how hard they try. Their minds race with worry and anxiety. They get restless. They wake up in a panic and can’t get back to sleep. They snore loudly and wake up constantly. They have flashbacks of their childhood abuse. They’re afraid to sleep. Their beds have become torture chambers. This also takes a metabolic toll.

On a daily basis, sleep, light, and circadian rhythms have important effects on symptoms. People with mood disorders can experience fluctuations based on the time of day; this is called diurnal variation. Some wake up feeling very depressed, but their moods improve as the day goes on. People with dementia can get agitated and more confused at night—something called sundowning. Likewise, some people with schizophrenia can get more symptomatic at night, too. The brain energy theory offers a new way to understand these well-known phenomena through mitochondria and metabolism.

Seasons can also affect symptoms. People with seasonal affective disorder, or depression during the winter months, are largely thought to be suffering from reduced exposure to sunlight. People with bipolar disorder can experience manic and depressive episodes around the change in seasons. The brain energy theory offers a new way to understand these changes, too.

Sleep, Light, and Circadian Rhythms as Treatment

Adequate sleep is critically important to mental and metabolic health. There are many ways it can play a role in treatment.

First, you might want to assess your sleep using these basic questions (any “no” responses are worrisome):

If you have chronic sleep problems, talk with your healthcare professional to determine what might be causing them. You might have obstructive sleep apnea, restless legs syndrome, a hormonal imbalance, or other reason for your sleep problem. Interventions such as sleep hygiene and cognitive behavioral therapy for insomnia (CBT-I) can play a role in treatment. These can be done in person with a therapist, but both are now accessible over the internet, too.

Sleeping pills, including over-the-counter supplements such as melatonin, can be helpful as short-term interventions for unusually stressful situations. However, 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. Try to normalize your sleep without the use of pills. If you’ve been using sleeping pills for years, you may need professional help to get off them.

Next, assess your light exposure (any “no” responses may be problematic).

Correcting any problems with light exposure, either not enough during the day or too much at night, can play a role in treatment.

Bright-light therapy is an intervention that involves sitting in front of a light every morning for about thirty minutes. These are special lights that are 10,000 lux (a measure of light intensity) that mimic exposure to sunlight but are generally safe on the eyes. 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. I should warn you that I have seen some patients with bipolar disorder develop hypomania and even mania from bright-light therapy, so please use it cautiously if you have had mania in the past.

I also mentioned brain photobiomodulation. This is still considered experimental but is being studied for a variety of conditions, such as dementia, Parkinson’s disease, stroke, traumatic brain injury, and depression.

Summing Up

Success Story: Kaleb—A Twelve-Year-Old Boy Struggling in School

Kaleb lived in an upper-middle-class town and had a reasonably good life, although his parents were divorced (one on the list of adverse childhood experiences). He also had a strong family history of mental illness—his mother, father, aunts, uncles, and grandparents had suffered from depression, suicide attempts, substance abuse, bipolar disorder, and/or schizophrenia. Beginning in preschool, he had difficulties. As he grew older, he clearly met the criteria for ADHD; he ran wild at times and was often distractible. He would get frustrated with schoolwork and throw tantrums.

He started psychotherapy. His parents and teachers tried many interventions, both disciplinary strategies and behavioral rewards. Nothing worked. He started a stimulant for his ADHD, which helped for about a week, but then he couldn’t sleep. That only made the problems worse. Different doses and different stimulants were tried, but the sleep problems weren’t improving. Sleeping pills were considered, but his parents decided to stop the stimulant instead.

His trouble at school worsened. His IQ and learning abilities were high; they weren’t the problem. He got support at school via an individualized education program (IEP), and eventually he was enrolled in a special education track for students struggling with social/emotional problems. He began reporting chronic depression. When frustrated, he would jab himself with a sharp pencil. When really frustrated, he would threaten suicide. In seventh grade, both the school and his therapist began recommending a mood stabilizer for presumed bipolar disorder. His parents refused and instead wanted to try a “metabolic” treatment plan.

We chose two interventions based on the metabolic basis of bipolar disorder. One issue we set out to address was insulin resistance. For the past couple of years, Kaleb had been gaining weight, especially around his waist, which is a marker of insulin resistance. He had taken to eating lots of sweets immediately after school “to deal with the stress of the day” and also after dinner “as a treat.” His parents allowed it given how stressful school had been for him. 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. This has been shown to be effective for bipolar depression, at least in some people, and it has few side effects.¹⁷ He already played video games every morning “to wake up,” so we introduced the bright light while he played his video games so that it didn’t require a change in his routine.

Within one month, things began to improve. His tantrums at school stopped. His depression and his focus improved. School was becoming more manageable for him.

The following year, in eighth grade, Kaleb got his best grades ever—straight As. In 2020, two years after beginning these interventions, he started high school during the COVID-19 pandemic. Although many of his peers were struggling with depression, anxiety, and social isolation, he thrived. He got straight As again and was taken off his IEP after the first semester. The new school couldn’t believe this well-behaved, top student was on an IEP in the first place.

Kaleb has been on this treatment plan for four years now and continues to thrive. Clearly, this specific plan won’t work for all kids who are struggling, but it worked for Kaleb. The brain energy theory helps us understand how and why.