Mitochondrial Dysfunction
When Mitochondria Malfunction
Descendants of an ancient bacterium that made its way into a single-cell organism perhaps two billion years ago, mitochondria inhabit all cells of the body except red blood cells. Their job is to respond instantly to circumstances, whether you need energy to jump out of bed, pick up your toddler, or write a speech. You can’t read, dream, or kiss a loved one without a shot of energy in your brain.
In a series of quick chemical cascades relying on available oxygen, mitochondria harvest electrons from the progressive breakdown of glucose to create ATP. As energy demands increase, mitochondria can divide and multiply on their own, and they constantly move around and reshape themselves through fission and fusion to maintain oxidative capacity under stress .
It would be one thing if energy production were all that mitochondria do. In fact, they do much more. They produce and regulate neurotransmitters, including serotonin, dopamine , and GABA. They regulate hormones , including cortisol, an agent of the stress response, and the hormones of reproduction: estrogen , testosterone , and progesterone. Mitochondria modify the expression of cellular genes , turning them on and off. Everything they do has a major effect on mental processes, from what you think to how you manage your emotions (or fail to), and how you interact with others.
The sensitivity of mitochondria to situational needs makes them the hub of adaptation to events within and without. But that sensitivity is double-edged: It puts mitochondria at risk from all kinds of environmental disturbances, leading to some form of mitochondrial dysfunction. Mitochondrial dysfunction of some kind is now thought to be the source of all psychiatric disorders. Reduced ATP production, for example, has been found in various parts of the brain in autism , bipolar disorder , depression , and schizophrenia.
Brain Metabolism in Psychiatric Disorders
Mitochondria are now seen as the unifying link for psychiatric illness because, as sensors of the internal and external environment, they must react quickly to changes in it. There are many ways the function of mitochondria can be reduced or impaired. Prolonged oxidative stress can erode their efficiency and activity or damage their genes. Sluggish debris removal can disrupt or impede activity.
Whatever the cause, the result is a decrease in energy production and an increase in ROS. Reduced brain energy is a source of fatigue and of cognitive fuzziness, and it especially undermines the brain’s most energy-intensive activity, executive function , affecting attentional focus, decision-making , impulse control, emotion regulation , and memory .
A mental state of challenge, stress consumes energy. Mitochondria generate the signals that enable adaptation to stress. And just as mitochondria respond to psychosocial experiences, they shape such experiences as well. Chronic stress affects many facets of mitochondrial biology, and changes in mitochondrial energy production capacity alter social behavior, stress reactivity, and mood. Changes in mitochondria are now believed to be a major way that adversity stamps biology , setting the stage for the development of disease.
Early life trauma, such as severe or multiple adverse childhood experiences (ACEs), appears to reprogram mitochondrial energetics. Researchers find that more mutations of mitochondrial DNA in adult women with major depression who had experienced parental loss or maltreatment in childhood compared to women without depression. Early damage to mitochondrial DNA can lastingly alter many elements involved in mitochondrial energy production.
Metabolic Treatment of Psychiatric Disorders
The new understanding of metabolic dysfunction as the common pathway of mental disorders ushers in not only a new approach to treatment but also a re-evaluation of existing treatments and a revised understanding of their value. There are already many known ways to influence metabolic function.
For example, it is well-established that some behaviors undermine mitochondrial function, and limiting them takes on a new urgency. Poor sleep and poor diet are among them. So is excessive stress. While it isn’t always possible to limit the amount of stress in one’s life, it is possible to learn, even at an early age, a wide range of all-purpose coping skills—from deep breathing to expressive writing to meditation .
There are also known measures that increase mitochondrial fitness. To all the well-established reasons for engaging in regular physical activity, add another— it boosts mitochondrial function. Physical exercise stimulates mitophagy, improving mitochondrial housekeeping and clearance of debris.
Among its many restorative functions, sleep counteracts oxidative stress. That, in fact, may be why we sleep. While we sleep, mitochondria are busy reshaping themselves to rebalance their energy-producing capacity. Sleep deprivation decreases their capacity to produce ATP. Sleep not only rejuvenates mitochondrial function, but good mitochondrial function is essential for the ability to sleep. It turns out that mitochondria play a central role in regulating the circadian clock that controls the sleep-wake cycle.
Explore More About Metabolism
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