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Potential Role in Schizophrenia
Synaptic pruning has been suggested to have a role in the pathology of neurodevelopmental disorders such as schizophrenia, as well as in autism spectrum disorder.  

Microglia have been implicated in synaptic pruning, as they have roles in both the immune response as macrophages as well as in neuronal upkeep and synaptic plasticity in the CNS during fetal development, early postnatal development, and adolescence, in which they engulf unneeded or redundant synapses via phagocytosis.   Microglial synapse engulfment and uptake has been specifically observed to be upregulated in the isolated synaptosomes of male patients with schizophrenia compared to healthy controls, suggesting upregulated microglia-induced synaptic pruning in these individuals. Microglia-mediated synaptic pruning has also been observed to upregulated during late adolescence and early adulthood, which could also account for the age of onset for schizophrenia often being reported around this time in development. The drug minocycline, a semisynthetic brain-penetrant tetracycline antibiotic, has been found to somewhat reverse these changes made to patient synaptosomes by downregulating synaptic pruning.

Genes in the Complement Component 4 (C4) locus of the major histocompatibility complex (MHC), which encode for complement factors, have also been tied to schizophrenia risk through gene linkage studies. The fact that some of these complement factors are involved in signaling during synaptic pruning suggests that schizophrenia risk may be linked to synaptic pruning. Specifically, complement factors C1q and C3 have been found to have a role in microglia-mediated synaptic pruning.   Carriers of C4 risk variants have also specifically been found to be tied to this kind of synapse overpruning in microglia. The proposed mechanism for this interaction is increased complement factor C3 deposition onto synaptosomes as a consequence of increased C4A expression in these risk variant carriers.