Inflammation and mitochondrial dysfunction in affective disorders-novel understandings, novel treatments?

Abstract

Background: Mitochondria are involved in energy production, oxidative balance, cell survival/apoptosis, immune response, and inflammation. A possible role in affective disorders has fueled research on mitochondrial targets for novel treatments. Methods: A systematic review of the literature was conducted, in Science Direct, Scopus and PubMed databases, from inception to 12th September 2022. Key words used were mitochondria AND/OR inflammation AND affective OR bipolar OR depression AND therapy OR treatment OR intervention. Results: Twenty-one studies were included in the analysis. Animal studies (n=16) have shown positive results for Nucleus Accumbens Deep Brain Stimulation (NAc DBS), Near-Infrared Photobiomodulation (NIR-PBM), exercise, 48-hour fasting, and fluoxetine, Li, valproate, BI-11A7 Bid inhibitor, methylene blue (MB), AC-5216, atractylenolide-III (ALT-III), ONO-2952, oxytocin (OT), tocopherol-a, Coenzyme Q10 (CoQ10). Human studies (n=5) have tested adjunctive therapies, with NAC plus antioxidant combination therapy, triacetyl-uridine (TAU), cytidine add-on, and andacetyl-l-carnitine and a-lipoic acid combination, with positive (TAU), negative, or difficult-to-interpret results. Limitations: The search was conducted on three databases only, and only articles written in English were included. Unpublished articles or research with negative results may have been missed. Conclusion: Mitochondria-targeting interventions are promising novel treatments for depression and bipolar disorder.

Keywords

• Bipolar disorder
• Depression
• Mitochondria
• Antioxidant
• Anti-inflammatory
• Anti-apoptotic