© 2003 by Oxford University Press and the Maryland Psychiatric Research Center (MPRC)
The Schizophrenia Prodrome Revisited: A Neurodevelopmental Perspective
Professor of Psychiatry, Albert Einstein College of Medicine Bronx, NY, Senior Research Scientist and Psychologist, The Zucker Hill side Hospital Glen Oaks, NY, and Director of the Recognition and Prevention (RAP) Program, The Zucker Hillside Hospital and Schneider Children's Hospital Lake Success, NY
Assistant Professor of Psychiatry, Albert Einstein College of Medicine Bronx, NY; Research Attending Psychologist in the Department of Psychiatry Research, The Zucker Hillside Hospital Glen Oaks, NY; and Associate Director, The Recognition and Prevention (RAP) Program of the Zucker Hillside Hospital and Schneider Children's Hospital Lake Success, NY
Assistant Director, the RAP Program
Research Scientist, Department of Psychiatry Research, The Zucker Hill side Hospital and Schneider Children's Hospital Glen Oaks, NY
Assistant Psychologist, the RAP Program Lake Success, NY
Assistant Psychologist, the RAP Program Lake Success, NY
Send reprint requests to Dr. B.A. Comblatt, The RAP Program, 444 Lakeville Road, Suite 303, Lake Success, NY 11042; e-mail: cornblat{at}lij.edu.
Despite the widespread acceptance of the neurodevelopmental model of schizophrenia, its application to research concerned with the prodromal phase of illness is limited. Little recognition has been given to the concept of an enduring biological vulnerability to illness that may be responsive to early intervention. Rather, the focus of most prodromal studies is on emerging positive symptoms. The Recognition and Prevention (RAP) program follows the strategy of being equally concerned with the nonspecific symptoms reflecting the core of schizophrenia and those directly related to psychosis. Data were collected from 62 adolescents (mean age = 16.4 years) during the ini tial 3-year pilot phase of the RAP program (1998–2001). Subjects were divided into three clinical high-risk groups, characterized by (1) negative and nonspecific symptoms (e.g., social isolation, school failures), the earliest prodrome stage; (2) emerging attenuated positive symptoms of moderate intensity; and (3) severe attenuated (but subpsychotic) positive symptoms, considered most proximal to psychosis. Four risk factors, derived from the neurodevelopmental literature, were selected to reflect the vulnerability core: cognitive deficits, affective disturbances, social isolation, and school failure. All four domains were equally impaired across the three risk groups, supporting the presence of the underlying vulnerability core regardless of the magnitude of emerging positive symptoms. An observational pilot study was also conducted to identify the medications typically used to treat emerging positive symptoms. Antidepressants were used as frequently as antipsychotics to treat adolescents presenting with moderate attenuated positive symptoms. Regardless of type of medication, moderately symptomatic youngsters did quite well over the approximately 1-year followup period. By contrast, adolescents presenting with more severe (but nonpsychotic) attenuated symptoms were treated with antipsychotics, often in combination with other agents. Outcome for the more symptomatic youngsters was, however, more guarded, with nearly half (i.e., 47%) of the group converting to a schizophrenia spectrum psychotic disorder. Nonadherence to medication appeared to be a major risk factor in this group. We conclude that a neurodevelopmental model of schizophrenia is supported by our data and that a range of novel treatment strategies may be neuroprotective by directly affecting the disorder's vulnerability core.
Keywords: Prodrome / schizophrenia / neurodevelop mental / clinical high risk / vulnerability / risk factors / attenuated positive symptoms / negative symptoms / antipsychotics / antidepressants
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