| مستخلص: |
The modern era of the treatment of major psychotic disorders started in 1927 when Manfred Sakel introduced the insulin-coma therapy but the real revolution came in 1938, when Lucio Bini and Ugo Cerletti documented the first therapeutic use of electrically induced seizures in humans. Later, in 1952 the first antipsychotic, cholpromazine was introduced by Henry Laborit, Jean Delay and Pierre Deniker while lithium was established in the 70s thanks to the works of Mogens Schou and Christian Baastrup. In 1957 antidepressants appeared, haloperidol was introduced in the 70s and second generation antipsychotics in the 90s. Valproate and carbamazepine were established in the 80s. Thus a variety of agents and therapeutic modalities are available today for the treatment of schizophrenia, bipolar spectrum disorders and other psychotic disorders and often are used in combination to treat clusters of symptoms with little concern for the primary diagnosis. In schizophrenia, which has a year prevalence of around 1 and life prevalence 1.4 in the general population and an incidence of around 10 per 10,000 [1], the advances in treatment made possible the release of a great number of patients from asylums, and gave a chance for the deinstitutionalization movement. However, recent data suggest that major impairment is still the rule rather than the exception. On the other hand, the treatment of BD (which has a lifetime prevalence of 3-6.5 including a wider spectrum of bipolarity in comparison to the DSM-IV-TR definition [2-4]) is complex and full of caveats for the clinician. Contrary to the approach by Kraepelin, today we know that a significant proportion of bipolar patients remain symptomatic and disabled, many of them suffering from subsyndromal depression and significant disability. Schizophrenia and bipolar disorder include patient adherence, long term clinical stability and prevention, treatment of comorbid depression and suicide and eventually the psychosocial rehabilitation and restoration of functioning and the treatment of the high rates of somatic morbidity and mortality. Social stigma represents another important issue. It is clear that the outcome of available treatment and care for major psychotic illnesses is suboptimal. These unmet needs should be addressed urgently, if the next generation of treatments is going to constitute a progress for the benefit of the patients. The excitatory aminoacids system and especially the NMDA receptor has been at the focus of research especially concerning schizophrenia and the knowledge on their involvement is coming of age. Several theoretical proposals for possible therapeutic targets in this system have been developed and the first clinical data have already appeared [5, 6]. The current supplement aims to explore the possible future role of agents acting on the NMDA receptor complex. In this frame, Xenia Gonda provided a short and comprehensive description of the basic pharmacology of these receptors [7]. Martin Bauer reviewed the data concerning the prodromal phase of schizophrenia, the limitations of the dopaminergic hypothesis and the possible importance of NMDA receptors in this process [8]. Thomas Schwartz reviewed genetic data supporting the NMDA glutamate receptor hypothesis for schizophrenia [9] and Corina Bondi comments on glutamatergic animal models of schizophrenia [10] while myself reviewed the possible involvement of NMDA glutamate receptor in the etiopathogenesis of bipolar disorder and its therapeutic implications [11] |