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Abnormal synaptic pruning during adolescence underlying the development of psychotic disorders
Monique Germann1, Sanne G Brederoo, Iris E C Sommer
1University of Groningen, Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, Groningen, The Netherlands.
Current Opinion in Psychiatry
|February 9, 2021
Summary
Excessive synaptic pruning contributes to schizophrenia (SCZ) pathophysiology. Targeting this pruning offers potential for early intervention and novel treatments for psychotic disorders.
Area of Science:
- Neuroscience
- Psychiatry
- Immunology
Background:
- Excessive synaptic pruning is a key factor in schizophrenia (SCZ) pathophysiology.
- Understanding aberrant synaptic pruning is crucial for SCZ research.
Purpose of the Study:
- Review recent developments in factors contributing to aberrant synaptic pruning in SCZ.
- Highlight the role of pruning in SCZ onset and cognitive symptoms.
- Identify potential prevention and treatment strategies for psychotic disorders.
Main Methods:
- Review of recent scientific literature on synaptic pruning in SCZ.
- Analysis of studies using positron emission tomography (PET) with [11C]UCB-J tracer.
- Examination of the roles of astrocytes, microglia, complement C4, and environmental factors.
Main Results:
- Positron emission tomography confirmed increased synaptic pruning and loss of synaptic density in SCZ.
- Astrocytes and complement-mediated microglial pruning (specifically by C4) contribute to SCZ.
- Environmental factors like infections and stress can influence microglial activation and pruning via dysbiosis.
Conclusions:
- The pruning machinery presents a potential therapeutic target for early SCZ treatment and prevention.
- Minocycline may improve SCZ cognition by reducing excessive pruning.
- N-acetyl-cysteine shows promise in restoring functional connectivity in SCZ.
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