Caught in vicious circles: a perspective on dynamic feed-forward loops driving oxidative stress in schizophrenia.

Details

Serval ID
serval:BIB_49CB12C0C114
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Caught in vicious circles: a perspective on dynamic feed-forward loops driving oxidative stress in schizophrenia.
Journal
Molecular psychiatry
Author(s)
Cuenod M., Steullet P., Cabungcal J.H., Dwir D., Khadimallah I., Klauser P., Conus P., Do K.Q.
ISSN
1476-5578 (Electronic)
ISSN-L
1359-4184
Publication state
Published
Issued date
10/11/2021
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: aheadofprint
Abstract
A growing body of evidence has emerged demonstrating a pathological link between oxidative stress and schizophrenia. This evidence identifies oxidative stress as a convergence point or "central hub" for schizophrenia genetic and environmental risk factors. Here we review the existing experimental and translational research pinpointing the complex dynamics of oxidative stress mechanisms and their modulation in relation to schizophrenia pathophysiology. We focus on evidence supporting the crucial role of either redox dysregulation, N-methyl-D-aspartate receptor hypofunction, neuroinflammation or mitochondria bioenergetics dysfunction, initiating "vicious circles" centered on oxidative stress during neurodevelopment. These processes would amplify one another in positive feed-forward loops, leading to persistent impairments of the maturation and function of local parvalbumin-GABAergic neurons microcircuits and myelinated fibers of long-range macrocircuitry. This is at the basis of neural circuit synchronization impairments and cognitive, emotional, social and sensory deficits characteristic of schizophrenia. Potential therapeutic approaches that aim at breaking these different vicious circles represent promising strategies for timely and safe interventions. In order to improve early detection and increase the signal-to-noise ratio for adjunctive trials of antioxidant, anti-inflammatory and NMDAR modulator drugs, a reverse translation of validated circuitry approach is needed. The above presented processes allow to identify mechanism based biomarkers guiding stratification of homogenous patients groups and target engagement required for successful clinical trials, paving the way towards precision medicine in psychiatry.
Pubmed
Web of science
Open Access
Yes
Create date
26/11/2021 19:12
Last modification date
04/12/2021 7:36
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