Neurodegenerative model of schizophrenia: Growing evidence to support a revisit

William S. Stone, Michael R. Phillips, Lawrence H. Yang, Lawrence S. Kegeles, Ezra S. Susser, Jeffrey A. Lieberman

Research output: Contribution to journalReview articlepeer-review


Multidimensional progressive declines in the absence of standard biomarkers for neurodegeneration are observed commonly in the development of schizophrenia, and are accepted as consistent with neurodevelopmental etiological hypotheses to explain the origins of the disorder. Far less accepted is the possibility that neurodegenerative processes are involved as well, or even that key dimensions of function, such as cognition and aspects of biological integrity, such as white matter function, decline in chronic schizophrenia beyond levels associated with normal aging. We propose that recent research germane to these issues warrants a current look at the question of neurodegeneration. We propose the view that a neurodegenerative hypothesis provides a better explanation of some features of chronic schizophrenia, including accelerated aging, than is provided by neurodevelopmental hypotheses. Moreover, we suggest that neurodevelopmental influences in early life, including those that may extend to later life, do not preclude the development of neurodegenerative processes in later life, including some declines in cognitive and biological integrity. We evaluate these views by integrating recent findings in representative domains such as cognition and white and gray matter integrity with results from studies on accelerated aging, together with functional implications of neurodegeneration for our understanding of chronic schizophrenia.

Original languageEnglish (US)
Pages (from-to)154-162
Number of pages9
JournalSchizophrenia Research
StatePublished - May 2022


  • Accelerated aging
  • Chronic schizophrenia
  • Cognition
  • Neurodegenerative processes
  • Neurodevelopmental hypothesis
  • White matter

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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