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Schizophrenia
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Schizophrenia is a neurodevelopmental mental disorder whose etiology includes genetic and environmental factors. Because of its early onset, chronicity, and characteristic interference with education, employment, and socialization, this illness represents a tremendous human and economic burden to those who suffer from it, their families, and society as a whole. Despite historical pessimism about schizophrenia prognosis, studies performed during the last decade suggest that early identification and intervention can improve outcome. These findings have stimulated great interest for the idea that intervention at or even prior to the onset of the first illness episode might improve subsequent treatment response and long-term outcome.
One aspect of this increased emphasis is to highlight the potential damage associated with delays in treatment of early phases of psychotic illness. Recent data indicate that duration of untreated psychosis (DUP) in schizophrenia first episodes consistently predicts outcome independently of other variables and is not simply a proxy for other factors. As one of the few potentially malleable factors influencing outcome, DUP could prove to be a target for secondary preventive efforts in early psychosis. A related recently developed concept is the notion of even earlier pharmacological intervention during the prodromal phase of schizophrenia. This concept is based upon the hypothesis that genetic liability for schizophrenia could be manifest in brain dysfunction leading to psychiatric, neuropsychological, and psychosocial impairments even without or before the full illness manifestations. The clinical applicability of this paradigm is presently assessed and it entitles the development of improved criteria for detecting individuals at high risk for developing schizophrenia and of specific and ethically acceptable treatments for this stage of illness.
The symptomatology of schizophrenia and related disorders includes positive psychotic symptoms (e.g. delusions and hallucinations), negative symptoms (e.g. impaired social skills, apathy, blunted affect, poor rapport), and widespread cognitive impairments affecting attention, memory, and learning capacities. Presently available medications are effective against positive symptoms, but they do not significantly improve negative symptoms and cognitive deficits. Moreover, their use implies patient exposure to a variety of side effects, including motor, Parkinson's disease-like symptoms, and metabolic side effects (e.g. obesity, blood sugar level elevation) that characterize second-generation antipsychotic drugs such as olanzapine (Zyprexa) and clozapine (Leponex).
During the last decade, our group has contributed extensively to the development and establishment of a novel class of medications to be used in psychotic disorders such as schizophrenia, and in illnesses such as autism, posttraumatic stress disorder, and Parkinson's disease (1-7). This class of medications affects brain neurotransmission mediated at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, and is designated as “glycine site agonists” of the NMDA receptor (substances that enhance the activity of the NMDA receptor.)" Typical representatives of these medications are glycine, D-serine, and sarcosine, which are natural amino acids that are present in the human body and thus have the advantage of being practically devoid of significant side effects. By now, studies performed by our and other research groups have demonstrated that these compounds have the capacity to significantly alleviate negative symptoms and cognitive deficits in schizophrenia subjects (1-5).
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2001