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Several studies have recently reported genetic linkage between markers located on the short arm of chromosome 6 and schizophrenia. Valid conclusions, however, are difficult to formulate because chromosomal markers that yielded positive results span a relatively large region of chromosome 6, and studies did not necessarily obtain consistent results with regard to the particular loci tested. Here, we report a meta-analysis of the results of linkage studies of schizophrenia that used chromosome 6p markers. After conducting a systematic search, nine different studies were selected for the analysis using defined criteria. Pooled P values were obtained for all common markers investigated and provided additional support for a major susceptibility locus for schizophrenia in this region. In addition, two markers located 2 cM apart, D6S274 and D6S285, provided the most significant results. These findings may help narrow the chromosomal region in the search for a major gene implicated in schizophrenia.

Although clozapine (CLZ) is effective in resistant schizophrenia, it fails in some cases leading to a therapeutic problem. Authors report a case of schizophrenia which resists several neuroleptic trials (including haloperidol, chlorpromazine and thioproperazine) and responds to a sequence of CLZ and amisulpride. These two atypical neuroleptics have the same main target (mesolimbic system) but have different and complementary affinities to neuromediator receptors: CLZ has strong serotoninergic and anticholinergic action, noradrenergic alpha 1 affinity and moderately active dopaminergic antagonism; amisulpride has a high and specific dopaminergic D2 antagonism when used at high posology. This clinical improvement can be related to "second treatment effect", described by Goldman in 1966: his study included two groups of refractory schizophrenic patients who received successively during two 6 months periods, 2 neuroleptics (fluphenazine and trifluperazine). Without initial therapeutic response, he noted a significant improvement only after change of neuroleptic medication. Tricyclic antidepressants may turn to be effective, after an initial failure, when they are given after an uneffective ECT trial. The same model may be applied and the clozapine-amisulpride sequence is proposed as an alternative treatment in resistant schizophrenia: even if CLZ is uneffective, it may produce carryover effects which ease the action of amisulpride. The hypothesis of an action on 5HT2-D2 antagonism is advanced. It leads to the general question of the opportunity of neuroleptic sequential prescription in resistant schizophrenia as a therapeutic option.

Through a review of the literature, the average mortality in schizophrenia is twice higher than among the population. This over mortality is highest among the 20-40 years range of age and added risk tends to disappear after 60 years. All studies stress the unnatural causes of death, suicide or accidental deaths. However several studies found an over mortality caused by natural death. The pathologies most often involved are: infections, lung, gastrointestinal, urogenital and cardiovascular diseases. Cancer mortality in schizophrenic patients is still debated. Some studies point out a reduced mortality compared to the general population whereas other studies find similar or over mortality. Nevertheless mortality ratio is found to be near 1 in the majority of studies. So it can be admitted that schizophrenic patient do really not differ from the general population in regard to cancer mortality. Premature death is highly linked to suicide. The epidemiological indicators that enable us to estimate the importance of suicide mortality are: the rate of suicide per 105 patients per year varies between 150 and 500, the percentage of death by suicide range between 10 and 15 percent. Suicide risk factors are numerous. Some of them are accepted as valid and others are still discussed. The former are: male gender, young and medium age ten first years of the illness course, associated depressive symptoms, past history of suicide attempts, iterative relapses and post hospital discharge period. The latter are: social isolation, celibacy, unemployment, high level of instruction, delusional and hallucinatory activity and familiar rejection.

The place of electroconvulsive therapy (ECT) in the treatment of affective disorders is presently important and even inequaled in some depressive illness forms. But ECT is still controversial and its indications in the treatment of schizophrenia remain debated. In order to evaluate the place of this "vielle thérapeutique du futur" (39) in the treatment of schizophrenia, we reviewed the literature of the two last decades and tried to answer these questions. 1) Is ECT effectiveness in treatment of schizophrenic symptoms proved? 2) What is the effectiveness of ECT compared with other efficacious treatment? 3) Does the ECT + neuroleptic combination provide some advantage? and in which cases? The literature provides many studies in the topic. However, a considerable proportion of these studies make no use of modern methodological criteria. We only consider papers which: --give a clear diagnostic definition in patients groups and control groups, --use a standardized method of treatment, --use quantitative tools to evaluate results, --randomize treatment and use, when possible, double blind design. 1) Curative effects of ECT in schizophrenic symptoms: Brandon et al. (14) compare two groups of schizophrenic patients diagnosed according to PSE for schizophrenia and receiving equivalent doses of neuroleptics. The first group receives ECT when the other one receives simulate ECT. The former improved significantly better than the later. The difference persists but is no longer significant from the forth week of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)