期刊
CURRENT OPINION IN PSYCHIATRY
卷 34, 期 3, 页码 222-227出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/YCO.0000000000000696
关键词
astrocytes; cognitive symptoms; microglia; schizophrenia; synaptic pruning
类别
资金
- ZonMw mental health (GGZ) (ZonMw) [63631 001 0]
The review highlights the importance of excessive synaptic pruning in schizophrenia and recent advancements in the field, focusing on the role of astrocytes and complement-mediated microglial pruning in disease onset and cognitive symptoms. The pruning machinery may be a potential target for early treatment and prevention of schizophrenia.
Purpose of review Excessive synaptic pruning has first been suggested by Irwin Feinberg (1982) as an important pillar in the pathophysiology in schizophrenia (SCZ). This article reviews recent developments highlighting factors implicated in aberrant synaptic pruning and its contribution to disease onset and emergence of cognitive symptoms in SCZ. Unraveling these factors provides new insights for potential prevention and treatment strategies for psychotic disorders. Recent findings Increased pruning in SCZ was recently confirmed by a positron emission tomography-study employing the novel tracer [11C]UCB-J, demonstrating the consequential loss of synaptic density. Recent evidence supports the contributing role of astrocytes and increased complement-mediated microglial pruning in disease onset and cognitive symptoms in SCZ. Increased microglial pruning is mediated specifically by C4. Furthermore, environmental factors (e.g., infections and stress) can lead to dysbiosis which was recently linked to microglial activation and pruning in SCZ. Recent findings render the pruning machinery a potential target for early treatment and prevention in individuals at high risk for SCZ. Minocycline can improve cognition in SCZ, probably by reducing excessive pruning. Probiotics might also have beneficial effects on cognition, although recent findings are not encouraging. N-acetyl-cysteine recovers functional connectivity in SCZ both in vitro and in vivo, making it an interesting candidate.
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