Thanks to important research on the connection between metabolic health and psychiatry, there is a greater understanding between mitochondrial health and mental health conditions such as depression. The researchers Chen et al. (2024) go on to state, "In recent years, more and more evidence show that the disorders of energy metabolism and mitochondrial quality control system caused by mitochondrial structural and functional disorders are also closely related to the pathogenesis of depression". Mitochondria are found in each of our cells and are known as the "powerhouse" that makes ATP, or energy, for our entire body - including our brains.
But here's where we have an update in the science:
Mitochondria have a greater impact than we originally thought - they also regulate information sent between nerves in the brain, release inflammatory cytokines, and activate the systemic inflammatory response.
Why does Mitochondrial Function Matter in Depression?
Neurotransmitter production
Neurotransmitters such as serotonin, dopamine, and norepinephrine play essential roles in mood regulation and production of neurotransmitters requires energy made by mitochondria.
Nervous system development
The development of our nervous systems require a tremendous amount of energy, or ATP which is made by mitochondria. Interestingly, autism spectrum disorder has been associated a higher rate of mitochondrial disease and dysfunction (Rossignol et al., 2012). Mitochondrial dysfunction appear be involved in other neurodevelopmental disorders such as Rett Syndrome and intellectual disability (Ortiz-González, 2021). Individuals with neurodevelopmental conditions have an increased risk of developing depressive symptoms.
Inflammation
Mitochondrial dysfunction is associated with increased inflammation. Let's look at this a little closer. When mitochondria don't work properly, it can trigger an inflammatory response and disrupt the immune system. This connection may help explain why inflammation is often seen in depression and other mental health conditions. Mitochondrial problems contribute to inflammation by way of oxidative stress.
Faulty mitochondria can't process oxygen properly, leading to a buildup of toxic free radicals and oxidative stress. This imbalance damages cells and activates the body's inflammatory response as it tries to neutralize the threat.
In integrative psychiatry, we can get a better sense of how your mitochondria are functioning through an organic acid test, which is a urine collection lab An organic acid test can detect oxidative stress through measurement of lipid peroxides and antioxidants like glutathione. Antioxidants get depleted when neutralizing oxidative stress. However, it is important to understand that there is not a single biomarker that will fully address the complexity of depression.
Mitochondrial Repair Therapy and Metabolic Psychiatry: A New Approach for Depression
By using therapies specifically designed to repair and improve mitochondrial health, scientists believe they may be able to alleviate some of the underlying biological factors contributing to depression. We might even consider this a metabolic subtype of depression that encompasses both inflammation and mitochondrial dysfunction.
This approach is mitochondrial function repair therapy, which aims to restore balance to the mitochondria and the critical roles they play. Decreasing inflammation goes alongside this.
Rather than just managing symptoms as is typical in conventional psychiatry, mitochondrial function repair therapy targets one of the root causes of cellular dysfunction seen in depression. Improving how mitochondria process oxygen, produce energy, and regulate other metabolic processes could help correct the imbalances that allow depression to take hold.
While still an emerging field, this line of research offers an exciting new perspective on treating mood disorders by focusing on optimizing the basic machinery that powers our cells and bodies. By boosting mitochondrial performance, it may be possible to lift the metabolic barriers associated with depression.
It's important to note that mitochondrial dysfunction is also thought to play an important role in other conditions such as chronic fatigue syndrome, traumatic brain injury symptoms, and long COVID.
Treatments that Repair Mitochondrial Function
Mitochondrial Functional Repair Agent | How it Works | Application in Depression | Sources |
CoQ10 | Antioxidant; Improves mitochondrial energy production; Enhances electron chain transport efficiency | Reduces oxidative stress | S. Andalib, M. Mashhadi-Mousapour, S. Bijani, M.J. Hosseini Coenzyme Q(10) alleviated behavioral dysfunction and bioenergetic function in an animal model of depression Neurochem. Res., 44 (5) (2019), pp. 1182-1191, 10.1007/s11064-019-02761-0 |
L-Carnitine | Facilitates fatty acid metabolism; Improves mitochondrial biogenesis | Increases energy production; Has neuroprotecdtive effects. Found to be particularly helpful for those taking Depakote. | G. Chen, W. Zhang, D. Li, J. Song, M. Dong Testosterone synthesis was inhibited in the testis metabolomics of a depression mouse model J. Affect Disord., 350 (2024), pp. 627-635, 10.1016/j.jad.2024.01.143 |
Alpha-lipoic acid | Antioxidant; Protects mitochondria | Supports overall mitochondrial health | R. Maiti, A. Mishra, B.R. Mishra, M. Jena Comparative efficacy of mitochondrial agents for bipolar disorder during depressive episodes: a network meta-analysis using frequentist and Bayesian approaches Psychopharmacol. (Berl.), 238 (12) (2021), pp. 3347-3356, 10.1007/s00213-021-06019-y |
Creatine | Supports ATP (energy) production | May increase energy availability in brain cells; Improves mitochondrial function | S.K. Bhullar, N.S. Dhalla Status of mitochondrial oxidative phosphorylation during the development of heart failure Antioxid. (Basel), 12 (11) (2023), p. 1941, 10.3390/antiox12111941 |
N-acetylcysteine (NAC) | Precursor to the antioxidant, glutathione | Reduces oxidative stress in the brain; Increases antioxidant capacity | M. Berk, A. Turner, G.S. Malhi, C.H. Ng, S.M. Cotton, S. Dodd, et al. A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo BMC Med., 17 (1) (2019), p. 18, 10.1186/s12916-019-1257-1 |
Rhodiola rosea | Adaptogen; Enhances stress resilience; Increases ATP production | May improve mood | B. Yang, Y. Xu, J. Yu, Q. Wang, Q. Fan, X. Zhao, et al. Salidroside pretreatment alleviates ferroptosis induced by myocardial ischemia/reperfusion through mitochondrial superoxide-dependent AMPKα2 activation Phytomedicine, 128 (2024), Article 155365, 10.1016/j.phymed.2024.155365 |
Omega 3 fatty acids | Supports cell membrane health | Reduces inflammation; Positively impacts mood and cognitive function | M. Lepretti, S. Martucciello, M.A. Burgos Aceves, R. Putti, L. Lionetti Omega-3 fatty acids and insulin resistance: focus on the regulation of mitochondria and endoplasmic reticulum stress Nutrients, 10 (3) (2018), p. 350, 10.3390/nu10030350 |
Evidence links mitochondrial dysfunction to depression. Studies show depressed patients have mitochondrial abnormalities like decreased ATP production. These deficits lead to inadequate energy supply, increased oxidative stress, and neuroinflammation - exacerbating depressive symptoms.
Targeting mitochondrial impairments may alleviate downstream effects like oxidative damage and inflammation that underlie mood disorders. Optimizing mitochondrial function presents a novel therapeutic approach for restoring neurological energy balance and reducing depression.
Other modalities shown to improve mitochondrial function and decrease both inflammation and oxidative stress include photobiomodulation. This is a non-invasive therapy that utilizes red-beam or near-infrared light therapy at a specific wavelength that works at the cellular level. We offer different forms of targeted photobiomodulation at our clinic and it is most effective when done three days a week for several weeks.
Interested in working with Dr. Burger and using an integrative treatment approach for depression or other mental health symptoms that involve metabolic psychiatry and mitochondrial function repair therapy? Learn more about becoming a patient here.
A kind reminder: This blog post is designed as a general guide. This is not a substitute for personalized medical advice, nor is a patient-physician relationship established in this blog post.
References:
Haiyang Chen, Mei Lu, Qin Lyu, Liuqing Shi, Chuntong Zhou, Mingjie Li, Shiyu Feng, Xicai Liang, Xin Zhou, Lu Ren (2024). Mitochondrial dynamics dysfunction: Unraveling the hidden link to depression, Biomedicine & Pharmacotherapy,175, 116656, https://doi.org/10.1016/j.biopha.2024.116656.
R. Ortiz-González (2021)l Mitochondrial Dysfunction: A Common Denominator in Neurodevelopmental Disorders?. Dev Neurosci 10 September, 43 (3-4): 222–229. https://doi.org/10.1159/000517870
Rossignol, D., Frye, R. (2012). Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry 17, 290–314. https://doi.org/10.1038/mp.2010.136