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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Insights into myelin dysfunction in schizophrenia and bipolar disorder
Marcela Valdés-Tovar, Alejandra Monserrat Rodríguez-Ramírez, Leslye Rodríguez-Cárdenas, Carlo E Sotelo-Ramírez, Beatriz Camarena, Marco Antonio Sanabrais-Jiménez, Héctor Solís-Chagoyán, Jesús Argueta, Germán Octavio López-Riquelme
Marcela Valdés-Tovar, Departamento de Farmacogenética, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City 14370, Mexico
Alejandra Monserrat Rodríguez-Ramírez, Leslye Rodríguez-Cárdenas, Carlo E Sotelo-Ramírez, Beatriz Camarena, Marco Antonio Sanabrais-Jiménez, Departamento de Farmacogenética, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City 14370, Mexico
Carlo E Sotelo-Ramírez, Jesús Argueta, Doctorado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City 09340, Mexico
Héctor Solís-Chagoyán, Jesús Argueta, Laboratorio de Neurofarmacología, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City 14370, Mexico
Germán Octavio López-Riquelme, Laboratorio de Socioneurobiología, Centro de Investigación en Ciencias Cognitivas, Universidad del Estado de Morelos, Cuernavaca 62209, Morelos, Mexico
Author contributions: Valdés-Tovar M contributed to the overall conception and design of the study; all authors carried out comprehensive literature search and wrote the first draft; Rodríguez-Ramírez AM contributed to the clinical perspective and figure design; Sotelo-Ramírez CE contributed to figure creation; Solís-Chagoyán H critically revised the manuscript; Valdés-Tovar M and Camarena B obtained funding; all authors assisted in a thorough revision of the manuscript and approved its final version.
Supported by Fondo Sectorial de Investigación para la Educación (FSIE SEP/CONACyT) to MV-T, No. 287115; and Fondo Sectorial de Investigación en Salud y Seguridad Social (FOSISS SS/IMSS/ISSSTE-CONACyT) to BC, No. 261459.
Conflict-of-interest statement: Dr. Valdés-Tovar has received research funding from Fondo Sectorial de Investigación para la Educación (FSIE), SEP-CONACyT and Dr. Camarena has received research funding from Fondo Sectorial de Investigación en Salud y Seguridad Social (FOSISS), SS/IMSS/ISSSTE-CONACyT, during the conduct of the study.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Marcela Valdés-Tovar, PhD, Research Scientist, Departamento de Farmacogenética, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada México-Xochimilco No. 101, Col. San Lorenzo-Huipulco, Tlalpan, Mexico City 14370, Mexico. mvaldes@imp.edu.mx
Received: May 31, 2021
Peer-review started: May 31, 2021
First decision: July 14, 2021
Revised: August 10, 2021
Accepted: January 17, 2022
Article in press: January 17, 2022
Published online: February 19, 2022
Processing time: 262 Days and 1.4 Hours
Schizophrenia and bipolar disorder are disabling psychiatric disorders with a worldwide prevalence of approximately 1%. Both disorders present chronic and deteriorating prognoses that impose a large burden, not only on patients but also on society and health systems. These mental illnesses share several clinical and neurobiological traits; of these traits, oligodendroglial dysfunction and alterations to white matter (WM) tracts could underlie the disconnection between brain regions related to their symptomatic domains. WM is mainly composed of heavily myelinated axons and glial cells. Myelin internodes are discrete axon-wrapping membrane sheaths formed by oligodendrocyte processes. Myelin ensheathment allows fast and efficient conduction of nerve impulses through the nodes of Ranvier, improving the overall function of neuronal circuits. Rapid and precisely synchronized nerve impulse conduction through fibers that connect distant brain structures is crucial for higher-level functions, such as cognition, memory, mood, and language. Several cellular and subcellular anomalies related to myelin and oligodendrocytes have been found in postmortem samples from patients with schizophrenia or bipolar disorder, and neuroimaging techniques have revealed consistent alterations at the macroscale connectomic level in both disorders. In this work, evidence regarding these multilevel alterations in oligodendrocytes and myelinated tracts is discussed, and the involvement of proteins in key functions of the oligodendroglial lineage, such as oligodendrogenesis and myelination, is highlighted. The molecular components of the axo-myelin unit could be important targets for novel therapeutic approaches to schizophrenia and bipolar disorder.
Core Tip: Schizophrenia and bipolar disorder are multifactorial neuropsychiatric entities that share clinical manifestations as well as alterations to brain structure and function, genetic characteristics, and neurobiological pathways. Among the main pathophysiological mechanisms shared by these conditions is oligodendroglial dysfunction. Scientific evidence that ranges from the microscale cellular and subcellular levels to the macroscale connectomic level strongly supports overall myelin dysfunction and brain disconnection as hallmarks of schizophrenia and bipolar disorder.
