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Adaptive changes to oxidative stress in schizophrenia

Molecular Psychiatry volume 27, pages 3565–3566 (2022)Cite this article

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Do & Cuenod have long argued that oxidative stress forms the core of pathophysiology in schizophrenia, inspiring many crucial investigations in this direction. In their most recent synthesis [1], Cuenod and colleagues go a step further and suggest that dynamic feed-forward loops exist among the major mechanistic pathways in schizophrenia, abetting oxidative stress across the course of neurodevelopment. They specifically argue for a vicious circle of cellular interactions centred around oxidative stress pathways initiated by either redox dysregulation, NMDA receptor hypofunction, neuroinflammation or mitochondria bioenergetics dysfunction. Accordingly, a dysregulation involving any one of these components can eventually amplify one another in positive feed-forward loops. They present extensive support for convincingly linking these mechanistic processes to oxidative stress and point out promising interventions to interrupt these vicious circles. I examine the central tenet of their argument i.e., a vicious cycle of pathophysiology begins from one of many mechanistic strands, but spirals over time to include several others, producing the phenotype of schizophrenia.

The explanatory framework of a vicious circle has an alluring appeal in pathophysiology. A vicious circle is said to exist when a presumed causal mechanism and its effect are so intertwined, that cause becomes effect, and the effect becomes cause [2]. When applied to biological phenomena, this metaphor further implies (1) some degree of loss of regulation/control, once triggered (2) ineffective compensatory feedback (3) progressive decompensation, potentially leading to depletion, if played out for sufficient time. Can we assume the redox system to be in this state—impaired regulation, failure of compensatory adaptation and progressive worsening—in schizophrenia?

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Funding

The author acknowledges salary support from the Tanna Schulich Chair of Neuroscience and Mental Health (Schulich School of Medicine, Western University, 2019–2022) and Monique H. Bourgeois Chair (McGill University).

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  1. Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Quebec, Canada

    Lena Palaniyappan

  2. Department of Psychiatry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada

    Lena Palaniyappan

  3. Department of Medical Biophysics, Western University, London, Ontario, Canada

    Lena Palaniyappan

  4. Robarts Research Institute, Western University, London, Ontario, Canada

    Lena Palaniyappan

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LP is the sole author that conceived, drafted and approved the final version this work.

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Correspondence to Lena Palaniyappan.

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The author reports personal fees from Otsuka Canada, SPMM Course Limited, UK, Canadian Psychiatric Association; book royalties from Oxford University Press; investigator-initiated educational grants from Janssen Canada, Sunovion and Otsuka Canada outside the submitted work.

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Palaniyappan, L. Adaptive changes to oxidative stress in schizophrenia. Mol Psychiatry 27, 3565–3566 (2022). https://doi.org/10.1038/s41380-022-01550-6

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