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Beyond comorbidities: metabolic dysfunction as a root cause of neuropsychiatric disorders

Published online by Cambridge University Press:  06 January 2025

Christopher M. Palmer*
Affiliation:
Director of the Department of Postgraduate and Continuing Education, McLean Hospital, Belmont, Massachusetts, USA, and an assistant professor of psychiatry at Harvard Medical School, Boston, Massachusetts, USA.
*
Correspondence Christopher M. Palmer. Email: cpalmer@mgb.org

Summary

Metabolic dysfunction has been long associated with severe mental illness (SMI), often viewed as a comorbidity to be managed. However, emerging evidence suggests that metabolic dysfunction, particularly at the mitochondrial level, may be a foundational element in the pathophysiology of neuropsychiatric disorders. This commentary expands on the current understanding by exploring the brain energy theory of mental illness, which posits that mitochondrial dysfunction is central to both metabolic and psychiatric conditions. The roles of insulin resistance, chronic stress and environmental factors are highlighted as shared biopsychosocial determinants that contribute to deterioration in both metabolic and mental health. The therapeutic potential of the ketogenic diet is discussed, particularly its ability to improve mitochondrial function and alleviate psychiatric symptoms. This shift in perspective, from viewing metabolic dysfunction as a secondary concern to recognising it as a root cause of SMI, has significant implications for clinical practice and research. By focusing on bioenergetic deficits and mitochondrial health, psychiatry may advance towards more effective, integrated treatment approaches that target the underlying cellular dysfunctions driving both metabolic and mental illnesses.

Type
Commentary
Copyright
Copyright © The Author(s), 2025. Published by Cambridge University Press on behalf of Royal College of Psychiatrists

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Footnotes

Commentary on… Metabolic dysfunction in severe mental illness. See this issue.

References

Fizíková, I, Dragašek, J, Račay, P (2023) Mitochondrial dysfunction, altered mitochondrial oxygen, and energy metabolism associated with the pathogenesis of schizophrenia. International Journal of Molecular Sciences, 24(9): 7991.CrossRefGoogle ScholarPubMed
Kim, J, Wei, Y, Sowers, JR (2008) Role of mitochondrial dysfunction in insulin resistance. Circulation Research, 102: 401–14.CrossRefGoogle ScholarPubMed
Monzel, AS, Enríquez, JA, Picard, M (2023) Multifaceted mitochondria: moving mitochondrial science beyond function and dysfunction. Nature Metabolism, 5: 546–62.CrossRefGoogle Scholar
Needham, N, Kamenská, I, Meadowcroft, B, et al (2025) Metabolic dysfunction in severe mental illness: updates on prevalence, aetiology and treatment options. BJPsych Advances, this issue [Epub ahead of print] 4 Nov 2024. Available from: https://doi.org/10.1192/bja.2024.52.Google Scholar
Ng, F, Berk, M, Dean, O, et al (2008) Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. International Journal of Neuropsychopharmacology, 11: 851–76.CrossRefGoogle ScholarPubMed
Ni, P, Ma, Y, Chung, S (2024) Mitochondrial dysfunction in psychiatric disorders. Schizophrenia Research, 273: 62–77.CrossRefGoogle ScholarPubMed
Orsolini, L, De Berardis, D, Volpe, U (2020) Up-to-date expert opinion on the safety of recently developed antipsychotics. Expert Opinion on Drug Safety, 19: 981–98.CrossRefGoogle ScholarPubMed
Palmer, CM (2022) Brain Energy: A Revolutionary Breakthrough in Understanding Mental Health – and Improving Treatment for Anxiety, Depression, OCD, PTSD, and More. BenBella Books.Google Scholar
Rho, JM (2017) How does the ketogenic diet induce anti-seizure effects? Neuroscience Letters, 637: 410.CrossRefGoogle ScholarPubMed
Scaini, G, Andrews, T, Lima, CNC, et al (2021) Mitochondrial dysfunction as a critical event in the pathophysiology of bipolar disorder. Mitochondrion, 57: 2336.CrossRefGoogle ScholarPubMed
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