Sphingolipid mechanisms in schizophrenia and its pharmacotherapy

Müller CP, Chestnykh D, Lourdusamy A, Alzheimer C, Gulbins E, Kornhuber J, Kalinichenko L (2026)

Publication Type: Journal article, Review article

Publication year: 2026

Journal

Current Opinion in Physiology Elsevier

Book Volume: 49

Article Number: 100972

DOI: 10.1016/j.cophys.2026.100972

Abstract

Schizophrenia is a debilitating mental disorder whose nature is still a conundrum, and for which treatments are still not fully satisfactory. While numerous alternative pathogenic processes are discussed, a common end path where they converge may still not be excluded. Accumulating evidence strongly suggests that schizophrenia symptoms arise from a progressive functional dysconnectivity in multiple neuronal circuits of the brain. The search for key mechanisms responsible for dysconnectivity identified oligodendroglia and their myelination of neuronal projections as a potential key pathogenic basis. It was suggested that this leads to synaptic dysfunctions in networks, resulting in a decline and disengagement of otherwise highly convergent information processing. A key pathological process, emerging now, may be a developmentally emerging or induced disturbance in dynamic sphingolipid regulation within oligodendrocytes. This will lead to a disruption in the dynamics of cerebral network myelination. Resulting unsystematic dyscoordination of conduction speed and lack of information convergence will then blur network efficacy and distort information processing. Here, we review the evidence suggesting the brain sphingolipid system as a potential nodal point in the pathogenesis of schizophrenia. New evidence suggests components of the sphingolipid system as a druggable target for a better therapy of schizophrenia.

Authors with CRIS profile

Peter Christian Müller Department of Psychiatry and Psychotherapy Daria Chestnykh Department of Psychiatry and Psychotherapy Christian Alzheimer Lehrstuhl für Physiologie Johannes Kornhuber Lehrstuhl für Psychiatrie und Psychotherapie Liubov Kalinichenko Department of Psychiatry and Psychotherapy

Involved external institutions

Nottingham Trent University GB United Kingdom (GB) Universitätsklinikum Essen DE Germany (DE)

How to cite

APA:

Müller, C.P., Chestnykh, D., Lourdusamy, A., Alzheimer, C., Gulbins, E., Kornhuber, J., & Kalinichenko, L. (2026). Sphingolipid mechanisms in schizophrenia and its pharmacotherapy. Current Opinion in Physiology, 49. https://doi.org/10.1016/j.cophys.2026.100972

MLA:

Müller, Christian P., et al. "Sphingolipid mechanisms in schizophrenia and its pharmacotherapy." Current Opinion in Physiology 49 (2026).

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