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Brain maturational processes and delayed onset in schizophrenia

Published online by Cambridge University Press:  01 September 1999

MATCHERI S. KESHAVAN
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic
GERARD E. HOGARTY
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic

Abstract

The central feature of schizophrenia is its onset in adolescence. Although this clinicalobservation is consistent with the view that schizophrenia may be a neurodevelopmentaldisorder, debate has focused on when the proposed brain maturational deviations may begin andwhat might be the nature of such defective development. Conflicting models of this illness (e.g.,the early and late neurodevelopmental models) have been proposed. In this paper, we will firstreview concepts from basic developmental neurobiology pertinent to these issues; we thensummarize aspects of the neurobiology of schizophrenia that have a particular bearing on theadolescent onset of this illness. We propose that the schizophrenic syndrome may result fromearly brain adversity and late maturational processes of brain development interacting withadverse humoral, biochemical, and psychosocial factors during adolescence and early adulthood.The onset of schizophrenia in adolescence may be related to the “plasticity switch”secondary to the peripubertal brain maturational changes, perhaps involving an alteration inglutamate receptor function. This loss of plasticity could result in social and nonsocial cognitivedeficits that are central to the pathophysiology of schizophrenia; the vulnerable person maytherefore utilize prepubertal processing styles that are insufficient to the adaptive and“gistful” abstraction requirements of adult cognition. Schizophrenia onset mightoccur in the context of psychosocial developmental challenges to a delayed social cognitivecapacity among neurodevelopmentally compromised individuals. We review therapeuticimplications as well as testable predictions generated by this model, and discuss researchstrategies that might further our understanding of the brain maturational abnormalities inschizophrenia.

Information

Type
Research Article
Copyright
© 1999 Cambridge University Press

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