NEURODEVELOPMENTAL AND NEUROPROGRESSIVE PROCESSES IN SCHIZOPHRENIA : Antithetical or Complementary, Over a Lifetime Trajectory of Disease? - 08/09/11
Résumé |
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.41 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?126, 186 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,174, 175, 185 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.69, 185 This debate as to origin(s) and course(s) of illness48, 133, 179 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.
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| Address reprint requests to John L. Waddington, PhD, DSc, Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland The authors' studies are supported by the Stanley Foundation. |
Vol 21 - N° 1
P. 123-149 - mars 1998 Retour au numéro
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- CHEMICAL AND PHYSIOLOGIC BRAIN IMAGING IN SCHIZOPHRENIA
- Richard J. McClure, Matcheri S. Keshavan, Jay W. Pettegrew
- EMERGING ROLES FOR NOVEL ANTIPSYCHOTIC MEDICATIONS IN THE TREATMENT OF SCHIZOPHRENIA
- Candace Andersson, Miranda Chakos, Richard Mailman, Jeffrey Lieberman
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