第8章
The Root Causes: What Disrupts Brain Energy?
If all mental disorders are metabolic disorders with mitochondria as the common pathway, then all known risk factors must connect directly to metabolism. Most people develop mental illness through multiple contributing causes, not a single root cause.
Genetics and Epigenetics: Despite extensive research through genome-wide association studies, researchers found almost no genes conferring significant risk to a significant portion of people with mental disorders. The few rare genes identified aren't specific to individual disorders but instead confer risk across multiple psychiatric, metabolic, and neurological conditions. Many identified risk genes directly relate to mitochondria and metabolism, such as DISC1 (influencing mitochondrial movement and function) and CACNA1C (affecting oxidative stress and mitochondrial integrity).
Epigenetics-the field studying what causes genes to turn on or off-provides additional answers. Epigenetic factors include DNA methylation, histone modifications, and other mechanisms influenced by diet, exercise, drug use, hormones, light exposure, and sleep-all related to metabolism and mitochondria. These epigenetic patterns can be inherited through the womb environment, early life experiences, and intergenerational transmission of trauma.
Neurotransmitters and Medications: The brain energy theory doesn't reject the chemical imbalance observations or the effectiveness of psychiatric medications, but offers deeper understanding. Mitochondria and metabolism explain both underactivity and hyperexcitability of brain cells that result in neurotransmitter imbalances. Neurotransmitters aren't simple on/off signals but exist in a complex feedback cycle with mitochondria-each affecting the other's function and balance.
Hormones: All hormones impact mitochondrial function and cause epigenetic changes in target cells, altering cellular metabolism. Cortisol, insulin, estrogen, and thyroid hormone all show profound connections to both metabolic and mental health. For instance, insulin resistance precedes psychosis development-children with persistently high insulin levels from age nine were five times more likely to develop psychosis risk and three times more likely to be diagnosed with bipolar disorder or schizophrenia by age twenty-four.
Inflammation: Inflammation plays a crucial role in metabolism, mitochondrial function, and both mental and metabolic health. Inflammation and mitochondria exist in a complex feedback loop. Mitochondria regulate many aspects of inflammation, both activating and deactivating it, while inflammation can impair mitochondrial function. Mitochondrial dysfunction can also trigger inflammation, creating a vicious cycle.
Sleep, Light, and Circadian Rhythms: Mitochondria are synchronized with our circadian rhythms, with energy production decreasing at night for sleep and increasing during the day for activity. Sleep deprivation impairs mitochondrial function in multiple brain regions, particularly in the hypothalamus which regulates metabolism and hormones. Different wavelengths of light affect mitochondria differently-red light tends to stimulate ATP production, while blue light inhibits it and increases ROS production.
Diet and Gut Health: What we eat, when we eat, and how much we eat directly affect metabolism, mitochondria, and mental health. Several vitamin deficiencies directly cause mental and neurological disorders that can be completely resolved by correcting the deficiency. Thiamine, folate, and vitamin B12 deficiencies are particularly important, as these vitamins are essential for mitochondrial energy production. The gut microbiome influences obesity, diabetes, cardiovascular disease, depression, anxiety, autism, schizophrenia, bipolar disorder, eating disorders, epilepsy, and neurodegenerative conditions through multiple mechanisms that ultimately affect mitochondrial function.
Drugs and Alcohol: Substances directly impact metabolism and mitochondria. Most drugs either stimulate or inhibit cells, with many having receptors directly on mitochondrial membranes. Alcohol is processed through enzymes that can lead to toxic acetaldehyde buildup, causing mitochondria to swell, struggle with ATP production, and generate excess reactive oxygen species. Studies show even short periods of heavy drinking cause lasting mitochondrial damage, particularly in the brain's hippocampus.
Physical Activity: Exercise shows strong correlations with better mental health. Exercise induces mitochondrial biogenesis and mitophagy in both muscle and brain cells, though several factors can limit its effectiveness for those with mental disorders. Insulin resistance can dampen or even reverse exercise benefits at the cellular level, and medications like metformin and antipsychotics that cause metabolic disturbances may prevent the full benefits of exercise.
Love, Adversity, and Purpose: Humans are hardwired to need purpose, and lacking it appears to induce chronic stress responses leading to poor health outcomes. Research confirms that purpose correlates with better metabolic and mental health outcomes. Stress diverts metabolic resources throughout the body, putting cellular maintenance on hold. When prolonged, this can lead to maintenance problems in cells, especially those not being used much, potentially causing symptoms of mental and metabolic disorders.
