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February 4 - April 8, 2025
Illnesses and symptoms are like traffic jams. Either traffic isn’t flowing optimally, or it stops altogether.
Just like some roads are more susceptible to traffic jams, some cells are more susceptible to metabolic failure.
metabolism is, in fact, the only way to connect the dots of mental illness. It is the lowest common denominator for all mental disorders, all of the risk factors for mental disorders, and even all of the treatments that are currently used.
However, when people are exposed to numerous stressors all at once, or when the stressors are extreme or overwhelming (such as being violently assaulted), these normal and understandable initial reactions can quickly lead to what we call “mental illness.”
I think biological, psychological, and social factors are all interconnected and inseparable. Biology influences our psychology and how we get along with others. But our psychology and our interactions with other people influence our biology.
There are countless reasons that humans stress other humans. And interestingly, the absence of other humans, or loneliness, is also a powerful stressor unto itself.
stress response includes changes in four domains: 1.The hypothalamic-pituitary-adrenal (HPA) axis, which results in cortisol flowing through the bloodstream; 2.The sympathetic-adrenal-medullary (SAM) axis, which results in adrenaline (epinephrine and norepinephrine) flowing through the bloodstream; 3.Inflammation; 4.Changes in gene expression, especially in the hippocampus.1 All of these changes, in turn, affect metabolism.
stress response takes a toll—a metabolic toll. The body uses energy to produce these changes, meaning less energy is available for other functions.
if a body is metabolically compromised, or if the stress is extreme, people can be pushed over the edge, and a new mental or metabolic disorder can quickly emerge.
Stress can exacerbate every known mental and metabolic disorder. People with depression may get more depressed. People with alcoholism may fall off the wagon. People with schizophrenia may hallucinate. People with Alzheimer’s disease may get agitated and combative. People with epilepsy may experience a seizure. People with diabetes may have their blood sugar skyrocket. And people with cardiovascular disease may have chest pain or a heart attack. Some people die—from stress alone.
The more ACEs a child has, the more likely he or she will have poor health outcomes.
ACEs clearly affect mortality.
having six or more ACEs takes twenty years off a person’s life compared to those with no ACEs.3
when the body is stressed, metabolic resources are being diverted to the fight-or-flight system. This leaves less energy available for other functions. Any cells that were already struggling can begin to fail. This can lead to metabolic and mental symptoms.
High levels of cortisol have been found to inhibit autophagy, slowing down or stopping this maintenance process.
Problems with autophagy have been found in a wide variety of disorders including neurodegenerative, neurodevelopmental, autoimmune, inflammatory, cancer, schizophrenia, bipolar disorder, autism, alcoholism, and major depression.5 Disturbances in autophagy are known to affect neuroplasticity and the maintenance of brain cells.6
when cells are stressed, they also slow the process of making new proteins. This appears to conserve metabolic resources for the body’s defense system. One way they delay making these proteins is by sequestering messenger RNA molecules (the instructions for new proteins) into little bubbles called “stress granules.”7 These have been associated with neurodegenerative disorders, and high levels of cortisol stimulate their production.8
Sleep is critically important to both physical and mental health. It’s a time when the body prioritizes maintenance functions.
The mothers with the highest levels of stress over the longest periods of time showed signs of accelerated aging compared to the lowest-stress women. On average, they aged ten years faster.
If the brain or body are already compromised and vulnerable, stress can make symptoms worse, because the energy needed for the stress response is diverting energy from these vulnerable cells.
we face a potentially overwhelming problem: with so many cells, it seems there’s an almost infinite number of ways that all of these “parts” could malfunction. For better or worse, this is where the mental health field has been focused, with researchers trying to understand how the machine works, step-by-step. It’s an overwhelming task, the notion of wholly mapping something as complicated as the human brain, and waiting for this work to be finished has arguably limited our progress in better understanding and treating mental illness.
These brain functions include things that relate to emotions, cognition, behavior, and motivation. As I will discuss, even some of the more bizarre-seeming symptoms of mental illness, such as delusions and hallucinations, can be tied to normal brain functions.
Overactivity of the pain system is when people experience pain more frequently or intensely than they should.
Underactivity can occur when people feel fewer pain signals than they should,
What makes it a disorder? The nerves can become injured from the pressure of the herniated disc. These injured nerves can become hyperexcitable. They can send pain signals too often or too intensely. The point at which the pain goes from a normal response to a disorder is difficult, if not impossible, to distinguish based on current diagnostic tests. In some cases, it’s not clear whether it’s normal or a disorder. However, when the pain becomes chronic, severe, and unprovoked, we call it a disorder.
A mental illness is when the brain is not working properly over a period of time, and this causes mental symptoms, which lead to suffering or impairment in functioning.
They will often deny any impairment in functioning. So, are these mental disorders? Yes. They are causing significant distress and/or impairment of functioning (this would include health problems), even if the person doesn’t see it or acknowledge it.
Fear and anxiety symptoms can result from hyperexcitability of the amygdala—one
Obsessions and compulsions can result from hyperexcitable cells and networks in the brain areas associated with grooming and checking behaviors.
Psychotic symptoms, such as hallucinations and delusions,
The easiest way to understand psychotic symptoms is hyperexcitability of brain cells that process perceptions.
Neurosurgeons can make people “hallucinate” by stimulating brain areas with an electrode. Hyperexcitable cells would be doing essentially the same thing.
“cortical interneurons.” These neurons are known to be inhibitory, as they secrete gamma-aminobutyric acid, or GABA, a neurotransmitter that slows activity in its target cells. Abnormalities in the function of these neurons have been found in many disorders, including schizophrenia, Alzheimer’s disease, epilepsy, and autism. This lack of inhibition would result in overactivity of the neurons they are supposed to be inhibiting.
psychotic symptoms are related to the sleep systems in the brain.
It’s possible that the same brain cells and networks that create these experiences at night are hyperexcitable and firing erroneously during the day in people with mental disorders.
hallucinations are not as uncommon as most people would think. Researchers have found that 12 to 17 percent of children ages nine to twelve and 5.8 percent of adults hallucinate during the day.
underactive function implies the cells are still alive and able to work at least some of the time. This is important, as it means that symptoms will wax and wane.
People with chronic mental disorders often have cognitive impairment, even if this isn’t part of their diagnostic criteria.
Although it commonly includes changes in mood, energy, appetite, and sleep, these changes can be very different in different people. Some people appear to have overactivity of the appetite system and others appear to have underactivity, resulting in eating too much or too little, respectively. Likewise, some people can sleep too much and others can’t sleep enough. Distilling depression into distinct symptoms, some that represent overactive or underactive brain regions, is likely to be the most effective and accurate way to understand depression,
This can also be normal. In fact, if it occurs in isolation, it’s not a diagnosable disorder according to DSM-5. Most people have experienced symptoms of hypomania at some point or another in life. This commonly occurs when people fall in love, but it can also occur when people are excited about a project or an accomplishment, or when they have a spiritual awakening.
These multifaceted brain adaptations become disorders when they are overactive.
It’s no wonder that the puzzle of mental illness has been so difficult to solve. What makes different parts of the brain overactive or underactive, leading to symptoms of mental illness? What makes the symptoms wax and wane? What exactly is causing these developmental abnormalities or areas of cell shrinkage and death? Why are they different in different people?
The drivers of human cells, and human metabolism, are called mitochondria. And they are the common pathway to mental and metabolic disorders.
mitochondria are the “powerhouses of the cell.” Mitochondria make energy for cells by turning food and oxygen into ATP.
the first mitochondrion (mitochondria is the plural of a single mitochondrion) was a bacterium. Researchers estimate mitochondria evolved from an independent living organism sometime between one and four billion years ago.
Although mitochondria and chloroplasts have different names, they look and function similarly, and they are thought to be descended from the same bacterium from billions of years ago. Furthermore, it’s believed that this merger happened only once, and that all plants, animals, algae, and fungi that exist today descended from this same organism.
The first is that evolution tends to get rid of things that are not essential or don’t confer some advantage in terms of survival or reproduction. If organisms evolve to no longer need a trait, it will no longer be selected for and will often eventually disappear.
The second is that new genes and traits must develop with and adapt to the genes and traits that are already there. Mitochondria were in eukaryotic cells first.
Over time, the nucleus and other organelles developed. As important as these other organelles are, mitochondria were there first. They likely influenced the development of these other cell parts and became indispensable. In fact, the...
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Mitochondria and human cells are now 100 percent committed to each other. Neither can survive without the other.
