The Role of Mitochondria in Mood Disorders: From Physiology to Pathophysiology and to Treatment

Giménez‐Palomo, Anna; Dodd, Seetal; Anmella, Gerard; Carvalho, André F.; Scaini, Giselli; Quevedo, João; Pacchiarotti, Isabella; Vieta, Eduard; Berk, Michael

doi:10.3389/fpsyt.2021.546801

Cited by 69 publications

(65 citation statements)

References 371 publications

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“…The dysfunctional mitochondrial hypothesis is one of the current hypotheses that attempt to explain the origin of mood disorders. Many studies have confirmed that mood stabilizers affect mitochondrial functions, even though the exact mechanism or localization of action is unknown [ 347 ].…”

Section: Diseases Linked To Mitochondrial Dysfunctionmentioning

confidence: 99%

Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System

Tanaka

Szabó

Spekker

et al. 2022

Cells

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Nearly half a century has passed since the discovery of cytoplasmic inheritance of human chloramphenicol resistance. The inheritance was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, a number of mutations in mtDNA were identified as a cause of severe inheritable metabolic diseases with neurological manifestation, and the impairment of mitochondrial functions has been probed in the pathogenesis of a wide range of illnesses including neurodegenerative diseases. Recently, a growing number of preclinical studies have revealed that animal behaviors are influenced by the impairment of mitochondrial functions and possibly by the loss of mitochondrial stress resilience. Indeed, as high as 54% of patients with one of the most common primary mitochondrial diseases, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, present psychiatric symptoms including cognitive impairment, mood disorder, anxiety, and psychosis. Mitochondria are multifunctional organelles which produce cellular energy and play a major role in other cellular functions including homeostasis, cellular signaling, and gene expression, among others. Mitochondrial functions are observed to be compromised and to become less resilient under continuous stress. Meanwhile, stress and inflammation have been linked to the activation of the tryptophan (Trp)–kynurenine (KYN) metabolic system, which observably contributes to the development of pathological conditions including neurological and psychiatric disorders. This review discusses the functions of mitochondria and the Trp-KYN system, the interaction of the Trp-KYN system with mitochondria, and the current understanding of the involvement of mitochondria and the Trp-KYN system in preclinical and clinical studies of major neurological and psychiatric diseases.

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Section: Diseases Linked To Mitochondrial Dysfunctionmentioning

confidence: 99%

Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System

Tanaka

Szabó

Spekker

et al. 2022

Cells

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“…Mitochondria are cellular organelles involved in energy production and several other biological processes, such as regulating oxidative stress and apoptosis. A relationship between mitochondrial dysfunction, characterised by impairments in energy production and increased oxidative stress and depression, has been reported in a wide range of studies on cell cultures, animal models, and clinical research [ 146 – 149 ]. Consequently, interest in treatments that target mitochondria dysfunction is on the rise.…”

Section: Curcumin’s Potential Antidepressant Mechanisms Of Actionmentioning

confidence: 99%

Potential Role of Curcumin for the Treatment of Major Depressive Disorder

Lopresti

2022

CNS Drugs

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Curcumin is the major biologically active polyphenolic constituent in the turmeric plant (Curcuma longa) that has been shown to have antioxidant, anti-inflammatory, neuroprotective, anticancer, antimicrobial, and cardioprotective effects. Interest in curcumin as a treatment for mental health conditions has increased and there is an expanding body of preclinical and clinical research examining its antidepressant and anxiolytic effects. In this narrative review, human trials investigating the effects of curcumin for the treatment of depression or depressive symptoms are summarised. Using findings from in vitro, animal, and human trials, possible biological mechanisms associated with the antidepressant effects of curcumin are also explored. To increase the understanding of curcumin for the treatment of depression, directions for future research are proposed. Key PointsEvidence from animal and human trials confirms curcumin is a promising treatment for depression.Curcumin has multiple biological actions that may account for its antidepressant effects.More research is required to increase the understanding of the antidepressant effects of curcumin.

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“…The dysfunctional mitochondrial hypothesis is one of current hypotheses attempts to explain the origin of mood disorders. Many studies have confirmed that mood stabilizers affect mitochondrial functions, even though the exact mechanism or localization of action is unknown [314].…”

Section: Bipolar Disordermentioning

confidence: 99%

Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan-Kynurenine Metabolic System

Tanaka¹,

Szabó²,

Spekker³

et al. 2022

Preprint

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Nearly half a century has passed since the discovery of cytoplasmic inheritance of human chloramphenicol resistance. The inheritance was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, a number of mutations in mtDNA were identified as a cause of severe inheritable metabolic diseases with neurological manifestation, and the impairment of mitochondrial functions has been probed in the pathogenesis of a wide range of illnesses including neurodegenerative diseases. Recently growing number of preclinical studies has revealed that animal behaviors are influenced by the impairment of mitochondrial functions and possibly by the loss of mitochondrial stress resilience. Indeed, as high as 54% of patients with one of the most common primary mitochondrial diseases, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, present psychiatric symptoms including cognitive impairment, mood disorder, anxiety, and psychosis. Mitochondria are multifunctional organelles which produce cellular energy and play a major role in other cellular functions including homeostasis, cellular signaling, and gene expression, among other. Mitochondrial functions are observed to be compromised and to become less resilient under continuous stress. Meanwhile, stress and inflammation have been linked to the activation of the tryptophan (Trp)-kynurenine (KYN) metabolic system, which observably contributes to development of pathological conditions including neurological and psychiatric disorders. This narrative review discusses the functions of mitochondria and the Trp-KYN system, the interaction of the Trp-KYN system with mitochondria, and the current understanding of the involvement of mitochondria and the Trp-KYN system in preclinical and clinical studies of major neurological and psychiatric diseases.

show abstract

The Role of Mitochondria in Mood Disorders: From Physiology to Pathophysiology and to Treatment

Cited by 69 publications

References 371 publications

Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System

Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System

Potential Role of Curcumin for the Treatment of Major Depressive Disorder

Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan-Kynurenine Metabolic System

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