Elucidating the pathogenesis of schizophrenia

BMJ 2003; 327 doi: https://doi.org/10.1136/bmj.327.7416.632 (Published 18 September 2003) Cite this as: BMJ 2003;327:632
  1. Akira Sawa, director (asawa1@jhmi.edu),
  2. Atsushi Kamiya, postdoctoral fellow
  1. Cellular Neurobiology Laboratory, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Meyer 2-181, Baltimore, MD 21287, USA

    DISC-1 gene may predispose to neurodevelopmental changes underlying schizophrenia

    Genetic predisposition to schizophrenia is evident from family, twin, and adoption studies.13 But whereas genetic factors contribute to the fundamental mechanisms or vulnerability to schizophrenia, additional influences including environmental factors are clearly involved in the full manifestation of symptoms of schizophrenia.4 Thus currently schizophrenia is best conceptualised as a “multiple hit” illness similar to cancer. This editorial looks at the fundamental mechanisms underlying the disease.

    The following evidence implies that neurodevelopmental abnormalities contribute to susceptibility to schizophrenia.1 5 6 7 Firstly, clinical studies show that patients with schizophrenia manifest minor behavioural abnormalities in childhood even before the onset of schizophrenia.

    Secondly, recent advanced imaging techniques such as magnetic resonance imaging provide reliable evidence of abnormalities during development of the central nervous system. Such abnormalities include consistent increases in ventricular size at the onset of schizophrenia, with notable alterations in some areas including the prefrontal cerebral cortex and hippocampus.

    Thirdly, neuropathological studies …

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