Despite the wealth of neuroimaging and neuropathologic evidence for abnormalities of brain structure and function in schizophrenia that has evolved over the past two decades, considerably less is known of their origins or of how they might relate mechanistically to the clinical features and the course of the disorder.<sup>41 Carpenter W.T., Buchanan R.W. Schizophrenia N Engl J Med 1994 ;  330 : 681-690  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> In the 1980s, there emerged renewed interest in an old and neglected question, the apparent answer to which continues to exert a powerful influence over contemporary research and theory: Do these abnormalities reflect a brain that was once normal but that became subject to some later pathological process (at or somewhat before the onset of psychosis), or do they reflect a brain whose early development was disrupted so as to preclude the development of normal cerebral structure and function?<sup>126 Murray R.M., Lewis S.W. Is schizophrenia a neurodevelopmental disorder? BMJ 1987 ;  296 : 681-682  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 186 Weinberger D.R. Implications of normal brain development for the pathogenesis of schizophrenia Arch Gen Psychiatry 1987 ;  44 : 660-669

Cliccare qui per andare alla sezione Riferimenti</sup> Epidemiologic (see article by Jones elsewhere in this issue) and neuropathologic (see article by Kleinman elsewhere in this issue) evidence synergise in contemporary emphasis on schizophrenia as a neurodevelopmental disorder,<sup>174 Waddington J.L. Schizophrenia: Developmental neuroscience and pathobiology Lancet 1993 ;  341 : 531-536

Cliccare qui per andare alla sezione Riferimenti, 175 Waddington J.L., Buckley P.F.   The Neurodevelopmental Basis of Schizophrenia Austin: Landes (1996). 

Cliccare qui per andare alla sezione Riferimenti, 185 Weinberger D.R. From neuropathology to neurodevelopment Lancet 1995 ;  346 : 552-557  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> and the ascendancy of this perspective has implications that extend beyond causal theorizing to other equally material aspects thereof; for example, in relation to course of illness, it has been argued that schizophrenia is, therefore, a static (i.e., nonprogressive) condition, in a manner antithetical to active (i.e., progressive) disease as encapsulated in classic Kraepelinian deterioration.<sup>69 Goldberg T.E., Hyde T.M., Kleinman J.E. , e al. Course of schizophrenia: Neuropsychological evidence for a static encephalopathy Schizophr Bull 1993 ;  19 : 797-804

Cliccare qui per andare alla sezione Riferimenti, 185 Weinberger D.R. From neuropathology to neurodevelopment Lancet 1995 ;  346 : 552-557  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> This debate as to origin(s) and course(s) of illness<sup>48 DeLisi L.E. Is schizophrenia a lifetime disorder of brain plasticity, growth and aging? Schizophr Res 1997 ;  23 : 119-129  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 133 O'Connell P., Woodruff P.W.R., Wright I. , e al. Developmental insanity or dementia praecox: Was the wrong concept adopted? Schizophr Res 1997 ;  23 : 97-106  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 179 Waddington J.L., Scully P.J., Youssef H.A. Developmental trajectory and disease progression in schizophrenia: The conundrum, and insights from a 12-year prospective study in the Monaghan 101 Schizophr Res 1997 ;  23 : 107-118  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> is surely fundamental to any meaningful concept of schizophrenia.

The present article has a threefold purpose: First, the recent proposals for network pathophysiologies that seek to unite otherwise diverse abnormalities of brain structure and function and the extent to which they might contain clues to their origin are considered. Second, indices of early developmental disturbance and the extent to which such putative network dysfunction can be related thereto are examined. Third, from such a developmental anchor, a cascade process for schizophrenia that encompasses a later, progressive element to the disorder is articulated.