Mitochondrial Dysfunction in Psychiatric Disorders: What Research Shows

Everything that performs a function requires energy. From the devices used in everyday life and the complex systems that sustain the human body. The brain is particularly demanding of energy. The adult brain consumes approximately 20% of the body’s energy, while energy demands can be even higher during childhood (Ni et al., 2024).

The brain depends on a highly complex system of structures and processes that work together to maintain normal functioning. This includes large-scale anatomical structures, such as the cerebral hemispheres, as well as microscopic processes involving neurons, synaptic connections, and cellular organelles such as mitochondria.

Function and Dysfunction in Mitochondria

Mitochondria are organelles inside the cell that respond to internal and external cues. One of their main functions (besides homeostasis, among others) is energy metabolism (Kim et al., 2019). They obtain energy from nutrients such as glucose and fatty acids through metabolic processes. These processes contribute to the production of adenosine triphosphate (ATP), the main energy-carrying molecule used by cells. Mitochondria also generate reactive oxygen species (ROS) and heat (Sorrentino et al., 2018).

When mitochondrial dysfunction occurs, several cellular processes may become disrupted. ROS production may become unbalanced, while energy production and mitochondrial signalling could also be affected. As a result, mitochondrial dysfunction can lead to reduced energy availability and alterations in processes necessary for normal cellular functioning (Sorrentino et al., 2018).

How Mitochondrial Dysfunction Affects the Brain

Psychiatric disorders have been associated with changes in several biological processes, including metabolism and circadian rhythms. The circadian rhythm helps regulate processes such as sleep, eating, and daily activity, while metabolism is responsible for converting nutrients into energy. Mitochondria play an important role in both cellular metabolism and the body’s ability to respond to changes in energy demands.

The brain derives energy from mitochondria, which manufacture adenosine triphosphate (ATP) molecules. ATP is a key energy carrier in the brain and enables neurons to communicate and conduct proper brain activities (Ni et al., 2024).

Mitochondria can be damaged or become less efficient. In that case, ATP decreases, and as a domino effect, neurons may not work as they should, which leads to the brain not performing normally. It’s harder for it to process information or regulate mood (as previously mentioned).

Several studies have identified mitochondrial abnormalities in individuals with psychiatric disorders. These findings have contributed to the hypothesis that impaired cellular energy production may affect brain function. However, current evidence does not establish mitochondrial dysfunction as a direct or independent cause of psychiatric disorders (Clay et al., 2011).

Yet, researchers haven’t discarded the possibility that mitochondrial dysfunction could potentially affect the brain. Particularly, there can be repercussions for how the brain works. Since the brain consumes high levels of energy to function, there can be a link to mitochondrial dysfunction. For this reason, researchers have investigated whether mitochondrial abnormalities may contribute to the development or progression of neuropsychiatric disorders (Ni et al., 2024).

Mitochondria and Oxidative Stress

Mitochondria not only regulate the energy produced and needed. It also, in their many functions, produces something called free radicals or reactive oxygen species. These free radicals, in normal amounts, are part of a healthy cell. But damaged mitochondria can produce an excessive amount of free radicals, and that is a problem. If the body defences can’t eliminate these free radicals fast enough, it leads to oxidative stress (Kim et al., 2019).

When that happens, there can be several consequences. Oxidative stress can damage proteins, DNA and cell membranes, and all of that decreases the neurons’ ability to communicate with each other. That is not the only thing that can happen. What can also happen is that the brain can present inflammation, which is also related to psychiatric conditions. For those reasons, research relates oxidative stress and mitochondrial dysfunction (or reduced energy production) to mental illnesses (Kim et al., 2019).

Mental Disorders Associated with Mitochondrial Dysfunction

As mentioned, mitochondrial dysfunction was associated with mental illness. From mood changes, seizures or even bipolar disorder. Even if all the research mentions that there is a need for further research, since there can be multiple factors involved in the development of mental illness interacting with each other, there is still a relationship being studied in the field of mitochondrial studies. Some of the mental illnesses related to mitochondrial dysfunction are:

Depression

Subjects in research who were diagnosed with depression also show lower levels of mitochondrial activity and decreased ATP production. That could be an indicator of decreased energy that would be an obstacle to the normal function of the brain (Ni et al., 2024).
But that was not the only result. Also, in patients with depression were seen an increased oxidative stress was observed. It may have contributed to inflammation of the brain and, as a consequence, led to changes in mood in damaged brain regions (Kim et al., 2019).
The combination of those two factors present in patients with depression and biological changes resulting from mitochondrial dysfunction and oxidative stress could be the reason for fatigue, poor concentration and low motivation (Gardner & Boles, 2011).

Bipolar Disorder

Unlike other mental illnesses, bipolar disorder was strongly associated in research with mitochondrial dysfunction (Scaini et al., 2021).

What studies found was that in people with bipolar diagnoses, there was increased oxidative stress and abnormalities in mitochondrial DNA, which could explain mood instability (Kato, 2017). How this exactly affects people with bipolar disorder remains unclear. These findings suggest that there is a relation between mitochondrial dysfunction and manic or depressive episodes (Ni et al., 2024).

Schizophrenia

A characteristic found in people with schizophrenia was the prevalence of type 2 diabetes. Talking about the brain, what happens is that a lack of oxygen in the brain cells leads to decreased activity, which also sends the signal for more glucose and activates oxidative stress. That condition is known as hypoxia, where cells are forced to alter metabolism (Prabakan et al., 2004).

Hypoxia and the demand for glucose are associated with oxidative stress, difficulty for cells to absorb dopamine and cognitive difficulties in the person. All of those are associated with schizophrenia (Prabakan et al., 2004).

Therapeutic Approaches Researched

The standard treatment for mental illnesses such as depression, bipolar disorder and schizophrenia includes medication regulated by medical staff and psychotherapy. But because of the possible relation to mitochondrial dysfunction, another point discussed by researchers was how to treat this.

First, oxidative stress. Antioxidants were discussed since they can reduce oxidative stress. Some of those, like coenzyme Q10 and acetyl-L-carnitine, among others. Still, these studies need to be taken with care, since the results are still inconsistent (including the direct relation between mitochondrial dysfunction and mental illness) (Berk et al., 2014).

Medicines were also taken into account for mitochondrial dysfunction, yet those studies are still in an experimental stage (Scaini et al., 2021). Finally, lifestyle habits also influence mitochondrial function. How? By doing regular physical activity, having a balanced diet, getting enough hours of sleep (regulated circadian rhythm) and good management of stress levels. Even if, by themselves, those actions can’t fully prevent or heal a mental illness, they can support and complement another treatment (Picard et al., 2018).

Conclusion

Mitochondrial function has a fundamental role in supplying the energy required for normal brain function. If they don’t work efficiently, the brain cells receive less energy to work properly, and that can also lead to oxidative stress that, at the same time, can affect the communication between neurons. Research has related these processes to mental illnesses such as depression, bipolar disorder and schizophrenia because of the mood changes and cognitive processes found in studies of subjects with mitochondrial dysfunction.

But research is still on new ground, so much so that these results cannot be considered the only thing affecting the person, since there can be other factors such as genetics or environmental factors. Possible therapies for this are still in experimental phases, but having a healthy lifestyle is recommended.

References +

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