Synaptic Pruning in Schizophrenia: Manifestations and Antecedents

Schizophrenia (SCZ) is a complex neurodevelopmental disorder characterised by structural and functional abnormalities in the brain. The synaptic pruning (SP) hypothesis, originally proposed by Irvin Feinberg (1982), suggests that excessive SP during adolescence contributes to the pathogenesis of SCZ. SP is a normal neurodevelopmental process wherein redundant synapses are eliminated to refine neural circuits. However, in SCZ, SP is aberrant and manifests as widespread grey matter depletion, reduced dendritic spine density, and cognitive deficits. This paper explores the structural and functional consequences of abnormal SP in SCZ and its potential antecedents, such as complement component 4 (C4) overexpression, neuroinflammation, NMDA receptor dysfunction, genes, and environmental deprivation and insults. Understanding the interplay between SP and schizophrenia pathophysiology may provide crucial insights into its neurodevelopmental origins and novel treatment strategies, especially for children showing early signs of psychosis.