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.

BackgroundGeneral psychiatric and forensic psychiatric beds, supported housing and the prison population have been suggested as indicators of institutionalized mental health care. According to the Penrose hypothesis, decreasing psychiatric bed numbers may lead to increasing prison populations. The study aimed to assess indicators of institutionalized mental health care in post-communist countries during the two decades following the political change, and to explore whether the data are consistent with the Penrose hypothesis in that historical context.Methodology/Principal FindingsGeneral psychiatric and forensic psychiatric bed numbers, supported housing capacities and the prison population rates were collected in Azerbaijan, Belarus, Croatia, Czech Republic, East Germany, Hungary, Kazakhstan, Latvia, Poland, Romania, Russia and Slovenia. Percentage change of indicators over the decades 1989–1999, 1999–2009 and the whole period of 1989–2009 and correlations between changes of different indicators were calculated. Between 1989 and 2009, the number of general psychiatric beds was reduced in all countries. The decrease ranged from −11% in Croatia to −51% in East Germany. In 2009, the bed numbers per 100,000 population ranged from 44.7 in Azerbaijan to 134.4 in Latvia. Forensic psychiatric bed numbers and supported housing capacities increased in most countries. From 1989–2009, trends in the prison population ranged from a decrease of −58% in East Germany to an increase of 43% in Belarus and Poland. Trends in different indicators of institutionalised care did not show statistically significant associations.Conclusions/SignificanceAfter the political changes in 1989, post-communist countries experienced a substantial reduction in general psychiatric hospital beds, which in some countries may have partly been compensated by an increase in supported housing capacities and more forensic psychiatric beds. Changes in the prison population are inconsistent. The findings do not support the Penrose hypothesis in that historical context as a general rule for most of the countries.

Given the existing controversies on the course of cognitive changes in schizophrenia, differentiated approaches specifically focusing on the peculiarities of the clinical features and changes in specific cognitive domains could shed light on the trajectories of cognitive deficits in schizophrenia and spectrum disorders.

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Recent interest in the early course of schizophrenia accentuated altered cognition prior to the onset. Ultrahigh risk (UHR) individuals with attenuated positive symptoms and transient psychotic episodes demonstrate neurocognitive deficits across multiple domains such as memory, executive functioning, and processing speed which are consistent with similar disturbances identified in patients with a first episode of schizophrenia. Cognitive remediation (CR) approaches representing a broad set of activities are aimed to restore or improve cognitive functioning. CR proved to be effective in modulating the cognitive dysfunction in schizophrenia but is rarely used in ultrahigh risk individuals. From the clinical prospective, a better understanding of cognitive functioning in at-risk states is essential for the development of optimal early intervention models. In the review, we highlight the intervention targets, notably the specific cognitive deficits in at risk individuals which preceed the transition to psychosis and emphasize the need of the additional studies using CR approaches in UHR group aiming to enhance cognition and therefore mediate functional improvement.

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The results of the present study suggest that the different schizophrenic sub-types may differ in terms of DUI, likely due to different clinical severity and social functioning. Studies with larger samples are needed to confirm the data of the present study.