Schizophrenia is a chronic, complex and heterogeneous mental disorder, with pathological features of disrupted neuronal excitability and plasticity within limbic structures of the brain. These pathological features manifest behaviorally as positive symptoms (including hallucinations, delusions and thought disorder), negative symptoms (such as social withdrawal, apathy and emotional blunting) and other psychopathological symptoms (such as psychomotor retardation, lack of insight, poor attention and impulse control). Altered glutamate neurotransmission has for decades been linked to schizophrenia, but all commonly prescribed antipsychotics act on dopamine receptors. LY404039 is a selective agonist for metabotropic glutamate 2/3 (mGlu2/3) receptors and has shown antipsychotic potential in animal studies. With data from rodents, we provide new evidence that mGlu2/3 receptor agonists work by a distinct mechanism different from that of olanzapine. To clinically test this mechanism, an oral prodrug of LY404039 (LY2140023) was evaluated in schizophrenic patients with olanzapine as an active control in a randomized, three-armed, double-blind, placebo-controlled study. Treatment with LY2140023, like treatment with olanzapine, was safe and well-tolerated; treated patients showed statistically significant improvements in both positive and negative symptoms of schizophrenia compared to placebo (P < 0.001 at week 4). Notably, patients treated with LY2140023 did not differ from placebo-treated patients with respect to prolactin elevation, extrapyramidal symptoms or weight gain. These data suggest that mGlu2/3 receptor agonists have antipsychotic properties and may provide a new alternative for the treatment of schizophrenia.

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The combination of olanzapine and carbamazepine did not have superior efficacy to carbamazepine alone. The increases in weight and triglycerides observed during combination treatment are a matter of concern.

The concept of latent schizophrenia was developed by E. Bleuler (1911) and was further promoted in the studies of a number of research psychiatric schools of Europe, the United States, Japan, and other countries. In Soviet psychiatry, there is a long-established tradition of studying "soft" forms of schizophrenia (Kerbikov 1933; Rozenshtein 1933; Brukhanskii 1934). In the systematics of schizophrenia, developed by Snezhnevsky (1969) and his colleagues, sluggish schizophrenia is viewed not as an initial (prodromal) stage of schizophrenia, but rather an independent diagnostic category characterized by a slowly progressive course, subclinical manifestations in the latent period, overt psychopathological symptoms in the active period, and then by a gradual reduction of positive symptoms, with negative symptoms predominating the clinical picture during patient stabilization. Studies are reviewed examining the relationship of constitutional and genetic factors to the clinical manifestation of sluggish schizophrenia. Finally, the importance of methodological considerations and an examination of divergent factors in the U.S. and Soviet concepts of schizophrenia are presented.

A critical analysis of the main concepts of schizophrenia (from the Kraepelin paradigm to the current studies attempted to «destruct» schizophrenia as nosologically independent disease) is presented. In author's opinion, the elimination of schizophrenia may lead to negative consequences as in aspect of clinical practice (the diagnosis of schizophrenia provides information about disease course, clinical and social outcomes) as well as in aspect of denial of autochthonous (endogenous) origin of mental disorders that fall under this definition. Based on the current level of knowledge, manifestation of these disorders can't be well explained by the adverse effects of situational, psychogenic or somatogenic factors. The restriction of the definition of schizophrenia («process» schizophrenia) should be brought about by the elimination of a group of schizophrenia spectrum disorders (schizotypal disorder, schizoaffective disorder, delusional psychosis).