Caught in vicious circles: a perspective on dynamic feed-forward loops driving oxidative stress in schizophrenia.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
25
08
2021
accepted:
20
10
2021
revised:
18
10
2021
pubmed:
12
11
2021
medline:
26
5
2022
entrez:
11
11
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34759358
doi: 10.1038/s41380-021-01374-w
pii: 10.1038/s41380-021-01374-w
pmc: PMC9126811
doi:
Substances chimiques
Parvalbumins
0
Receptors, N-Methyl-D-Aspartate
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1886-1897Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2021. The Author(s).
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