Mitochondrial Metabolism in Major Depressive Disorder: From Early Diagnosis to Emerging Treatment Options.
Ane Larrea, Laura C Sánchez-sánchez, Eguzkiñe Diez-Martin, Ane Elexpe, María Torrecilla, Egoitz Astigarraga, Gabriel Barreda-Gómez
Journal of Clinical Medicine March 17, 2024 DOI: 10.3390/jcm13061727 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | Ketamine Esketamine Psychedelics Anti-inflammatories Transcranial Magnetic Stimulation Deep Brain Stimulation |
| Topics | Depression |
| Keywords | Inflammation Ketamine/esketamine Mitochondrial dysfunction Psychedelic Transcranial stimulation Clinical depression Neuroscience brain science Neurobiology Neural research Mental health interventions |
| Citations | 21 |
| Key findings | Mitochondrial dysfunction is a key factor in MDD pathophysiology, and mitochondrial biomarkers could improve diagnosis, while emerging pharmacological and non-pharmacological treatments offer alternatives to traditional antidepressants. |
Abstract
Major Depressive Disorder (MDD) is one of the most disabling diseases in the world. MDD is traditionally diagnosed based on a patient's symptoms, which can lead to misdiagnosis. Although the pathogenic mechanisms of MDD are unknown, several studies have identified mitochondrial dysfunction as a central factor in the onset and progression of MDD. In the context of MDD, alterations in mitochondrial metabolism can lead to imbalances in energy production and oxidative stress, contributing to the disorder´s underlying pathophysiological mechanisms. Consequently, the identification of mitochondrial dysfunction as a key biomarker for early and accurate diagnosis of MDD represents a significant challenge. Faced with the limits of traditional treatments with antidepressants, new pharmacological therapeutic targets are being investigated such as ketamine/esketamine, psychedelics, or anti-inflammatories. All of these drugs show potential antidepressant effects due to their speed of action and ability to modulate neuroplasticity and/or motor processing. In parallel, non-pharmacological therapeutic targets are studied, like Transcranial Magnetic Stimulation (TMS) and Deep Brain Stimulation (DBS), recognized for their ability to modulate neuronal activity and offer treatment alternatives. As cellular activity is directly related to mitochondrial respiration, the aim of this review is examining the link between mitochondrial dysfunction and MDD, assessing how mitochondrial biomarkers could provide a more objective and precise diagnostic tool, and exploring other treatments in addition to traditional antidepressants, with a specific focus on emerging therapeutic targets. Finally, a detailed analysis of the strengths, weaknesses, opportunities, and threats of these approaches was carried out, highlighting the key challenges that must be addressed.
Comparable studies
Other narrative reviews on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synaptic Dysfunction in Depression: Potential Therapeutic Targets | 2012 | Review | |
| Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse | 2003 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines | 2005 | Review |
Citations in the library
Cited by 3
- Psilocybin alleviates high-glucose and high-lipid-induced skin aging in BJ5Ta fibroblasts Biochemistry and Cell Biology 2025
- Exploring the Therapeutic Potential of Entheogens in Postoperative Cognitive Decline and Psychological Resilience ACS Medicinal Chemistry Letters August 21, 2024
- CB1R-dependent mitochondrial biogenesis may contribute to the antidepressant effects of esketamine in a chronic variable stress male mouse model. Neuroscience July 27, 2026
Cites 37
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
and 32 more in the library