Chapter 18

CONTRIBUTING CAUSE

Love, Adversity, and Purpose in Life

Metabolic and mental health require a combination of both biological and environmental factors. I’ve told you about many of the biological factors. The environment includes many things—food, shelter, temperature, light, infections, allergens, and lifestyle choices—some of which we’ve covered. But it also includes people, experiences, love, and purpose in life. Although most people see these latter constructs as psychological and social issues and often assume they aren’t related to biology, they actually play profound roles in metabolism. They are all interrelated and inseparable. We adapt and respond to our environments, for better or worse.

Use It or Lose It

The phrase “use it or lose it” is usually associated with exercise and muscle strength. When people use, or stress, certain muscles, they become larger and more resilient. Not only do they grow in size, but they also develop more mitochondria. This is true even when the size of the muscles isn’t that much larger. For example, some long-distance runners can be very thin. Their muscles aren’t all that big, yet they contain more mitochondria than the muscles of people who don’t run. These mitochondria give their muscles the endurance they need to go long distances.

Not using muscles results in atrophy, or shrinking. This can be striking when people break a bone and are in a cast for several weeks. Their muscles shrink rapidly. Why? When the body isn’t using something, it diverts metabolic resources from it. The body is always adapting and adjusting. It spends its energy wisely. If muscles aren’t being used, they don’t get much glucose or as many amino acids. They quickly shrink. The good news is that the body keeps a memory of what those muscles once were. Once the cast comes off, the muscles quickly return to their normal size if they get used in the same ways again. This truly depends on what size they were beforehand. Big bodybuilders will quickly regain their massive muscles, while frail, elderly people will only get a tiny amount of muscle growth.

This concept of “use it or lose it” applies to more than just muscles. It also applies to the brain. The best evidence for this comes from studies of children as their brains are developing.

Some human skills and traits need to be acquired at the right times. The brain undergoes “developmental windows” during which it is ready to learn and adapt. However, the “environment” must offer experiences needed to acquire these skills or else they can be altered for life. Social skills are one example.

Social skills are important to human survival. They allow us to live in families, towns, and societies. They require two things to develop properly: (1) normal brain development to acquire and store the information and (2) learning experiences from other humans. If either is absent, problems will be obvious. The biology side can be understood in terms of brain development, mitochondria, and metabolism, as I have already discussed. The environment side depends upon parents and caretakers primarily. There is a tremendous amount of literature looking at the effects of attachment, neglect, abuse, and social deprivation on human development. Many of us would say these things relate to love, or a lack thereof. They play a profound role in human development, including the acquisition of social skills. Children deprived of appropriate learning opportunities often lack the skills needed to navigate the world effectively. In extreme cases, the consequences can be catastrophic.

The findings of researchers studying Romanian orphans exemplifies how tragic this can be. The orphanages where these children were housed were profoundly neglectful, and the children who experienced this neglect were found to suffer from a range of diagnostic categories including autism, learning disorders, mental retardation, PTSD, anxiety disorders, impulse control disorders, mood disorders, personality disorders, and even psychotic disorders. Once again, numerous diagnostic categories, not just one. Their brains were deprived of the appropriate opportunities to learn how to be “human” in society and the consequences were sometimes devastating. The malnutrition, stress, and trauma they experienced undoubtedly also played roles, but so did the lack of appropriate learning experiences.

These children’s brains didn’t develop normally. If areas of the brain that perform certain functions aren’t being used, they don’t grow and thrive. One research group studied metabolic brain scans of ten such children and compared them to normal control and even epileptic children.¹ Sure enough, they found widespread areas of reduced brain glucose metabolism, indicating a brain energy problem in these former Romanian orphans. Sometimes, these deficits can be corrected later in life; but in some cases, they appear to be permanent. Developmental windows can close, and the opportunity for normal brain development can be lost forever.

It’s not always so extreme. For example, children exposed to more screen time are more likely to develop ADHD. There are two ways to interpret this observation. One explanation is that the environment is driving the subsequent diagnosis of ADHD. These children are learning that constant stimulation is the norm given the content on the screens. They are not learning patience, focus, and concentration even if their brains are ready to learn. These developing brain networks will receive fewer metabolic resources since they aren’t being used, much like the unused muscle. They may not develop normally, or they may not be as strong and robust as they could otherwise be. This can result in ADHD symptoms. However, it’s also possible that this could be due to reverse causation, and biology might be the problem. If these children have inadequate metabolism in specific brain regions, they may be unable to focus. This may drive them to use screens as a source of entertainment. If this explanation is correct, then correcting the metabolic issue will be the first step in solving the problem.

The concept of strengthening brain regions is obvious to most of us through clichés like “practice makes perfect.” This applies to learning a new language, playing basketball, or learning to play the piano. When we use our brains in specific ways, neurons grow, adapt, and form new connections. If we use them, they grow. If we don’t, they wither. This all relates to metabolism and mitochondria. They adapt to our needs.

Stress

I now return to stress. I have discussed this throughout the book and have already told you how it plays a powerful role in mental and metabolic health. I’ll review some highlights, share some new information, and then get to treatments.

Recall that the stress response requires energy and metabolic resources. These resources are being diverted from other cells throughout the brain and body, and these other cells can suffer. For example, if a young boy is chronically stressed, he will have more difficulty learning in school. It’s not necessarily because he isn’t trying. The stress response is taking energy that could otherwise be used for brain functions like focus, learning, and memory.

Stress puts cellular maintenance functions on hold. If it occurs for a prolonged period, it can result in maintenance problems in cells, especially ones not being used much, which can lead to symptoms of mental and metabolic disorders. Any cells that are already metabolically compromised can begin to malfunction under stress, which can exacerbate symptoms of mental and metabolic disorders.

In Part Two, I talked about how mitochondria play a critical role in the stress response. They influence all aspects of the stress response, including the production and regulation of key hormones and neurotransmitters, nervous system responses, inflammation, and epigenetic changes. When mitochondria are not functioning properly, all of these can be affected.

One research study demonstrated a direct relationship between everyday stress and changes in mitochondrial function in humans.² The researchers developed a test of mitochondrial health that includes both the quantity and function of mitochondria within white blood cells and assessed whether this metric was associated with daily stress. They studied ninety-one mothers, some who had children with autism and others who had neurotypical children, and assessed their daily mood and stress levels to see if these were related to the mitochondrial health index (MHI). They found that they were. Overall, the mothers who had high levels of stress and low moods had lower MHI. But of course, stress levels and moods can change on a daily basis. The researchers looked at this specifically. When the mothers were in a positive mood, the MHI went up afterward, sometimes within one day. In other words, the health and function of mitochondria in white blood cells were changing in response to the mothers’ daily moods and stress levels. This research demonstrates how stress can lead to impairment in mitochondrial function, which can then affect overall health.

All humans experience stressful life events. In the 1960s, Dr. Thomas Holmes and Dr. Richard Rahe, both psychiatrists, studied five thousand medical patients to see how stressful life events can contribute to physical illness. They identified some common life events and ranked them by how much they impacted overall health. The Holmes-Rahe Stress Inventory is still available today and can give you a sense of what life events are most stressful. Some top ones include the death of a spouse or close family member, divorce, personal injury, getting fired, and even retiring. These select ones involve some type of loss—losing someone important to you, losing your health, or losing your job (even voluntarily). What makes these so stressful? There are many reasons, and they can be different for different stressors, but one common theme is that they all relate to purpose in life.

Purpose in Life

Humans are driven to have a sense of purpose. I believe this is hardwired into our brains, given that this single construct has been highly associated with both metabolic and mental health. When people lack a sense of purpose, it appears to induce a chronic stress response and can lead to many poor health outcomes. Purpose in life is multifaceted, however. It usually includes many things, not just one. The stress inventory that I just mentioned highlights three possibilities: relationships, taking care of yourself and staying healthy, and having a job.

Dr. Viktor Frankl, an Austrian psychiatrist who was taken prisoner by the Nazis during World War II, deserves credit for highlighting the powerful role of meaning and purpose in life. In his book Man’s Search for Meaning, he described his observations of the other prisoners in the concentration camp. Most became severely depressed, for obvious reasons. However, some did not. Some of the prisoners appeared to hold on to hope that they might live and escape. Frankl argued that the common denominator among them was that they all had a sense of purpose in life: they had a reason to fight and try to stay alive.³ Frankl went on to develop a psychotherapy, logotherapy, based on the construct of meaning and purpose in life. Many of its tenets are still embedded in current mainstream psychotherapies.

The concept of purpose in life continues to be studied today and has been highly correlated with a wide range of metabolic and mental health outcomes. It’s not surprising that a low sense of purpose in life is associated with depression, given that depression itself might make people feel this way. It may just be circular logic. However, a lack of purpose is also associated with metabolic disorders and even longevity, consistent with the brain energy theory. For example, one study of nearly seven thousand US adults ages fifty-one to sixty-one found that those who had the lowest sense of purpose in life were about 2.5 times more likely to die an early death than those with a strong sense of purpose in life.⁴ They were dying of heart attacks, strokes, respiratory disorders, and gastrointestinal conditions. These researchers noted other studies showing that a strong sense of purpose leads to lower levels of cortisol and inflammation, which might explain these health benefits. A 2016 meta-analysis of ten prospective studies that included over 136,000 participants also found that having a higher sense of purpose in life was associated with reduced all-cause mortality and cardiovascular events.⁵

When discussing purpose in life, it’s important to include spirituality and religious beliefs. For many, these play a powerful role in how they understand their existence. Researchers have studied the effects of religious beliefs and practices on a variety of health outcomes and, in general, have found many beneficial effects. For example, one study looking at adults at high risk for depression found that those who reported religion or spirituality to be highly important were 90 percent less likely to develop depression compared to those who reported them of low importance.⁶ The researchers conducted brain scans on these people and found differences in the thickness of certain brain regions based on how important religion and spirituality were to the participants. These brain differences may explain the protection against depression. The Nurses’ Health Study followed almost ninety thousand women for more than fourteen years and found that women who attended religious services at least once per week were five times less likely to commit suicide than those who never attended religious services.⁷ A systematic review of religious beliefs and practices and their effects on health found a beneficial relationship with several other health outcomes, such as decreased rates of cardiovascular disease and all-cause mortality.⁸ One challenge with this type of data, however, is the possibility of reverse causation again—it might be that people who are already healthy are able to attend religious services and connect with people there, but people who are already depressed or metabolically compromised aren’t. Despite this possibility, I’ll soon share with you data that suggests some religious practices, such as meditation and ritual prayers, might directly help improve metabolism and mitochondrial health, so these may, in fact, play a causal role in improving health outcomes.

For those who don’t believe in God, I don’t mean to imply that you need to start believing in God to improve your health. I share this information because it relates to purpose in life and has been found to influence both metabolic and mental health. There are other ways to find purpose that can play just as powerful a role.

Addressing Love, Adversity, and Purpose with Treatment

All of this can play a role in treatment. First, it’s important to point out a general rule of thumb for human health—people need to develop and maintain full lives, ones that include what I call the four Rs: close relationships, meaningful roles in which they contribute to society in some way, adherence to responsibilities and obligations (not just to the people in one’s life, but to society as a whole, such as not breaking laws), and having adequate resources (money, food, shelter, etc.).

Many societal factors can interfere with people’s abilities to achieve all of this, including war, trauma, poverty, malnutrition, neglect, racism, homophobia, misogyny, all the ACEs, and so many others. Efforts are needed to address these social problems, for as long as these continue, mental illness will continue to exist. However, people who have been affected by these barriers and atrocities can still recover. They can use science-based approaches to understanding and addressing the impact of these experiences on their metabolism and mitochondria. I’m hopeful this book and the theory of brain energy will help at least some of them.

Psychotherapy

Addressing the myriad of psychological and social factors that can impact metabolism is an important part of treatment. Friends, family, coworkers, teachers, mentors, or people in the community can often help. Some people, however, will need professional help in the form of psychotherapy.

There are countless books and academic articles on how psychotherapy can improve mental health. I won’t even try to review all the research. Instead, I’ll share just a few of the benefits and some possible reasons why it works:

Psychedelic Therapy

One emerging treatment related to all of this is the use of psychedelic drugs in psychiatry. Hallucinogens, such as psilocybin or “magic mushrooms,” are receiving increasing attention as a possible treatment for depression, PTSD, and other conditions, with small pilot trials showing benefits. One research group explored how and why these work. They noted, “psychedelics can reliably and robustly induce intense, profound, and personally meaningful experiences that have been referred to as ‘mystical-type’, ‘spiritual’, ‘religious’, ‘existential’, ‘transformative’, ‘pivotal’ or ‘peak’.”⁹ They surveyed 866 users of psychedelics over time and found alterations in metaphysical beliefs that often persisted for longer than six months. These persistent metaphysical beliefs were correlated with improved mental health outcomes. This line of research suggests that psychedelics might work by connecting people with spirituality or God, or offering them a sense of meaning and purpose. I should point out that using these on your own is not recommended. The research trials are pairing the use of psychedelics with guided therapy sessions in order to maximize benefits. Using them on your own may result in a “bad trip” or could possibly even trigger a manic or psychotic episode.

Stress Reduction

Reducing stress is an important part of treatment. In addition to all the ways that psychotherapy and talking with other people can help reduce stress, there are two ways that people can do this on their own: (1) reduce or eliminate stressful environmental factors or (2) attempt to reduce your stress response when it is safe to do so.

The easiest way to manage stress is to reduce or eliminate stressors when possible. For some, this is a realistic goal. A highly demanding work or school environment that is overwhelmingly stressful can be managed. The employee can find a new job, or the student and parents can reduce course load, seek academic accommodations for a disability, or change schools to find a better fit. Creating a life that is manageable, pleasurable, and rewarding is something we should all strive to do.

When stressful life events occur, people will experience a stress response. This is normal and expected. But when the threatening situation is no longer a danger, reducing the stress response can have powerful, beneficial effects.

Stress-reduction practices have been used for millennia. Some of these are not usually thought of as “stress-reduction techniques,” but instead as longstanding religious practices, such as meditation, praying, and chanting. Additional practices include yoga, Pilates, tai chi, qigong, mindfulness, and breathing techniques. Many of these interventions have been shown to improve both mental and metabolic health. I won’t review all the interventions and health conditions, as there are many. However, I will share a couple of studies directly linking these benefits to metabolism and mitochondria.

Researchers from Harvard Medical School had long known that the relaxation response can play a powerful role in both mental and metabolic health. The relaxation response, or RR, is a term they use to describe any of the stress-reduction techniques I already mentioned, such as meditation. Studies have demonstrated improvement in hypertension, anxiety, insomnia, diabetes, rheumatoid arthritis, and aging itself. They set out to better understand how this intervention works. They recruited nineteen healthy, long-term practitioners of daily RR practice, nineteen healthy controls, and twenty people who recently completed eight weeks of RR training. They took blood samples from all of them and looked at differences in gene expression. For those doing RR, they found significant differences in genes related to “cellular metabolism, oxidative phosphorylation, generation of reactive oxygen species and response to oxidative stress.” As you now know, these are directly related to mitochondria.¹⁰

In a follow-up study, the researchers recruited twenty-six people who had been practicing regular RR techniques for four to twenty years and another group of twenty-six people who had never regularly practiced RR but were willing to complete eight weeks of training.¹¹ All the participants were then asked to listen to a twenty-minute RR recording and, in a different session, a twenty-minute health education recording. Blood samples were taken before, immediately after, and fifteen minutes after listening to each recording, and these samples were analyzed for gene expression. The researchers found that “RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways.” A specific mitochondrial protein (mitochondrial ATP synthase) and insulin were the top two upregulated molecules. These researchers concluded, “Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency . . . ” As you now know, this is precisely what we are trying to do to improve mental and metabolic health!

Rehabilitation Programs

Many people with chronic mental disorders lack the skills needed to independently survive and thrive in society. Some don’t know how to make friends. Others don’t know how to manage a daily schedule. Still others don’t know how to hold a job. Many feel they lack purpose in life.

Their symptoms prevent most of these people from doing these things. Even if they learned how to do them prior to their illness, they might now be out of practice. For those who developed their illnesses at a young age, they may never have learned these skills in the first place.

Restoring metabolic health to their brains won’t automatically teach them everything they need to know. They need training and practice. It’s like rehabilitation after a sports injury. You have to first restore the function of the muscles, bones, ligaments, or tendons, but then the person must also practice and build up strength again. Without this practice, abilities won’t be restored.

There are currently rehabilitation programs that offer education, job training, and basic life skills to people with chronic mental disorders. Unfortunately, current research suggests they aren’t very effective. This is likely because brain function was not restored first. If people are trying to do tasks when their brains aren’t working properly, they are being set up for failure. It’s like an athlete trying to run a marathon with a torn ligament. However, if we can restore proper brain function, then rehabilitation has a decent chance of working. The goal is to help people live as productive members of society. Many of them have been beaten down for years and may feel hopeless about this goal. This hopelessness also needs to be addressed.

In all of this, compassion from other humans is required. Job programs and reentry into society are needed. These people have to find reasons to live. They need to feel useful. They need to feel respected. All of this requires the involvement of other people.

Summing Up

Success Story: Sarah—Exercise and Finding Her Purpose

Sarah was seventeen years old when I first met her. She had been diagnosed with ADHD and a learning disability in the eighth grade, had suffered from anxiety and insomnia for as long as she could remember, and began having panic attacks at age fourteen. She was also depressed and had low self-esteem. She struggled in school, despite taking medications for her ADHD, and she had few friends. She had a strong family history of mental illness, with her mother, brother, sister, grandmother, two uncles, and an aunt all having been diagnosed with depression, anxiety disorders, and/or bipolar disorder. That didn’t bode well for her long-term outcome. She had already tried eight different medications, which helped with her ability to concentrate, but also came with side effects and continuing symptoms. She would sometimes get so depressed that she would stay in bed all day. On top of her mental symptoms, she also had migraine headaches and frequent stomach pains.

She got into college and did her best, but she struggled. Her family expected her to finish college, and this stressed her even more. She often felt that she could never live up to people’s expectations. She tried more antidepressants, but they didn’t help.

Things changed when she decided to take Pilates classes. She loved them! She began exercising regularly and noticed that many of her mood and anxiety symptoms were getting better. At age twenty-three, she got a job as an instructor at the studio—she was now exercising almost every day for hours per day. That was the game-changer for her. She came to an appointment after about two months on the job saying, “I feel great! I’ve never felt this good in my entire life.” On top of the exercise, she had become passionate about helping others improve their health, had made new friends, and now had a boyfriend. Despite her parents’ expectations that she finish college, she decided to drop out and focus on exercise as her career. That was almost ten years ago and Sarah continues to do well to this day. She still takes stimulant medication for her ADHD symptoms, but was able to stop all the other medications. After tapering off them, she said she actually felt even better.

Sarah’s story highlights the power of exercise as a metabolic treatment, but also the psychological and social aspects of finding meaning and purpose in life, stress-reduction practices, having a social support network, and not letting the expectations of others rule us. We are all different, and want—and need—different things. Sarah found her own way to metabolic and mental health.