Research Topic

Myelin and Oligodendrocyte Function as the Novel Treatment Targets of Serious Mental Illness (SMI)

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Schizophrenia (SZ) and Bipolar Disorder (BPD) are Severe Mental Illnesses (SMI) that affect 2-4% of the world population. SMI is a major cause of disability in young adults globally and significantly decreases the quality of life for patients. Additionally, patients with SMI often experience persistent ...

Schizophrenia (SZ) and Bipolar Disorder (BPD) are Severe Mental Illnesses (SMI) that affect 2-4% of the world population. SMI is a major cause of disability in young adults globally and significantly decreases the quality of life for patients. Additionally, patients with SMI often experience persistent cognitive impairments even in remission from psychopathological symptoms. Current medications for SZ and BPD do not show any beneficial effects on cognitive function. Thus, novel interventions that can improve cognitive and social functions in SMI are urgently needed.

Higher functions of the brain, such as perception, emotion regulation, and cognition, are considered the summative outcomes of the integrated activities of multiple brain regions. The “dysconnectivity” theory postulates that SMI results from the disrupted anatomical and functional connectivity among multiple brain regions. Numerous neuroimaging studies have found decreased integrity of major interregional White Matter (WM) tracts in patients with SMI. WM abnormalities in the fronto-limbic and fronto-temporal tracts have been associated with cognitive impairments and suicide attempts in SMI, indicating the critical role of WM in cognitive function.

Oligodendrocytes (OL) are the myelin-forming glial cells that compose WM tracts together with axons in the Central Nervous System (CNS). The lipid-rich myelin sheath acts as a high resistance electrical insulator around axons and maintains the integrity and function of interregional connectivity. OLs are sensitive to inflammation, oxidative stress and other insults and subject to cell death. Damage to the OLs leads to a decrease in conduction velocity and, when severe, cessation of conduction. Neuropathological and genetic studies show decreased OL cell numbers and altered myelin structure in cortical and subcortical areas of SZ and BPD. As the key contributors to the pathophysiology of SMI, WM and OL abnormalities may also be promising targets for SZ and BPD treatment.

This Research Topic for Frontiers in Psychiatry will focus on research progress in developing novel treatments of SZ or BPD by altering WM or OLs pathology, regeneration, or functions. We intend to cover broad research areas, from clinical trials to translational studies, using animal and tissue cultures. These studies will generate knowledge that will lead to a better understanding of the role of OL and WM pathology, and ultimately provide effective treatments for SMI, especially for cognitive impairments.


Keywords: White Matter, Cognitive Impairment, Schizophrenia, Bipolar Disorders, Oligodendrocyte Pathology, White Matter Pathology


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