Version 1
: Received: 26 March 2024 / Approved: 27 March 2024 / Online: 28 March 2024 (12:24:09 CET)
How to cite:
Sfera, A.; Imran, H.; Sfera, D.O.; Anton, J.J.; Kozlakidis, Z.; Hazan, S. The Future of Antipsychotic Interventions: From Managing Symptoms to Improving Outcomes. Preprints2024, 2024031692. https://doi.org/10.20944/preprints202403.1692.v1
Sfera, A.; Imran, H.; Sfera, D.O.; Anton, J.J.; Kozlakidis, Z.; Hazan, S. The Future of Antipsychotic Interventions: From Managing Symptoms to Improving Outcomes. Preprints 2024, 2024031692. https://doi.org/10.20944/preprints202403.1692.v1
Sfera, A.; Imran, H.; Sfera, D.O.; Anton, J.J.; Kozlakidis, Z.; Hazan, S. The Future of Antipsychotic Interventions: From Managing Symptoms to Improving Outcomes. Preprints2024, 2024031692. https://doi.org/10.20944/preprints202403.1692.v1
APA Style
Sfera, A., Imran, H., Sfera, D.O., Anton, J.J., Kozlakidis, Z., & Hazan, S. (2024). The Future of Antipsychotic Interventions: From Managing Symptoms to Improving Outcomes. Preprints. https://doi.org/10.20944/preprints202403.1692.v1
Chicago/Turabian Style
Sfera, A., Zisis Kozlakidis and Sabine Hazan. 2024 "The Future of Antipsychotic Interventions: From Managing Symptoms to Improving Outcomes" Preprints. https://doi.org/10.20944/preprints202403.1692.v1
Abstract
Abstract
For the past 70 years, dopamine hypothesis has been the key working model in schizophrenia. This has contributed to the development of numerous inhibitors of dopaminergic signaling, antipsychotic drugs, which led to rapid symptom resolution but only marginal outcome improvement. Over the past decades, there was limited research on the quantifiable pathological changes in schizophrenia, including premature cellular/neuronal, senescence, brain volume loss, attenuation of gamma oscillations on electroencephalogram and oxidation of lipids in plasma and mitochondrial membranes.
We surmise that aberrant activation of aryl hydrocarbon receptor by toxins derived from the gut microbes or the environment drives premature cellular, including neuronal, senescence, a hallmark of schizophrenia. Early brain aging promotes secondary changes, including impairment and loss of mitochondria, gray matter depletion, decreased gamma oscillations, and a compensatory metabolic shift to lactate and lactylation.
The aim of this narrative review is twofold:
1. To summarize what is known about premature cellular/neuronal senescence in schizophrenia or schizophrenia-like disorders.
2. To discuss novel strategies for improving long-term outcome in severe mental illness with natural senotherapeutics, membrane lipid replacement, mitochondrial transplantation, microbial phenazines, novel antioxidant phenothiazines, inhibitors of glycogen synthase kinase-3 beta, and aryl hydrocarbon receptor.
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
