Schizophrenia has long been understood primarily through the lens of neurodevelopmental hypotheses, which attribute the disorder’s origins to brain development abnormalities. A review evaluated recent research to reassess the neurodegenerative hypothesis in schizophrenia, a less accepted model which suggests that certain aspects of cognitive and biological integrity, such as white matter function, deteriorate beyond normal aging.

Historical perspectives noted the progressive nature of schizophrenia but lacked consistent post-mortem evidence of neurodegeneration. However, recent studies highlight biological dysfunctions in chronic schizophrenia, such as decreased dendritic spines and synaptic density, supporting a neurodegenerative process. Findings from cognitive studies show accelerated cognitive decline in older patients with schizophrenia, reinforcing the notion of progressive deterioration. White matter studies also reveal greater reductions in integrity with age in patients with schizophrenia compared to healthy controls. These observations suggest that schizophrenia involves both neurodevelopmental and neurodegenerative components, requiring a reevaluation of how these processes interact throughout the life span.

Reference: Stone WS, Phillips MR, Yang LH, Kegeles LS, Susser ES, Lieberman JA. Neurodegenerative model of schizophrenia: Growing evidence to support a revisit. Schizophr Res. 2022 May;243:154-162. doi: 10.1016/j.schres.2022.03.004. Epub 2022 Mar 25. PMID: 35344853; PMCID: PMC9189010.