Studies conducted in chronic patients (see Results) are limited by several factors:

• They focus on patients whose evolution is unfavorable and do not take those patients into consideration who recover after a first episode. 
• They are influenced by the impact of relapses inherent to the experience of chronic patients; these often aggravating relapses are likely to modify the response to treatment and do not allow to assess its effectiveness on initial symptoms of the disease. 
• Results are also influenced by the consequences of long term medication on the mechanisms of the disease. 

Studies focusing on persons experiencing the early phase of a psychotic disorder allow to avoid these biases and thus provide an opportunity to examine specificities intimately linked to the pathology itself in a group of patients representative of any possible evolution.

Furthermore, several investigations suggest that the first 5 years of psychotic disorders represent a "critical phase" during which the detrimental evolution of the disease could possibly be prevented. Other studies show that cerebral modifications appear at the time of transition to explicit psychosis (fully declared psychosis, beyond the stage of forerunners). 
It thus appears important to develop treatments which would allow to act on symptoms arising during the critical phase.  

Considering these elements, the trial presently conducted by the Unit for Research in Schizophrenia (URS) is aimed at evaluating the impact of NAC supplementation (N-acetyl-cysteine, new drug resulting from the URS research program) to standard neuroleptic treatments in patients during the first episode of a psychotic disorder.  

The randomized, double-blind, placebo-controlled trial lasts for a period of 6 months per patient.  It is planned to gradually include 80 to 100 patients. Half of the patients participating in the study receive NAC, the other half take a placebo (neutral substance); the distribution is carried out randomly. The study is conducted simultaneously in both groups; neither the patients nor the team responsible for the study know who receives NAC and who takes the placebo.

Several institutions in Lausanne collaborate on this project (CHUV, EPFL, UNIL) as well as a research group of the Psychiatric University Hospital in Basel, under the responsibility of Professor Anita Riecher-Rössler.
Furthermore, a team of the Harvard Medical School in Boston (USA), under the responsibility of professor Larry J. Seidman, is interested in the project and decided to participate in the study through conduction a similar trial, whose results will represent a valuable complement to the data obtained in Lausanne and Basel.

The study thus involves several research centers; it is conducted according to common parameters but its financing (in Switzerland and the United States) is entirely independant. The trial started at the beginning of 2009 and will mobilize a major part of the URS's means and clinical research staff during four years.

Besides the study in progress, the promising results achieved by the URS motivate the further development of its translational research programme, which includes:

• clinical research in patients, in particular during the early stages of the disease; an investigation concerning the impact of NAC during the prodromal phase of the disease, i.e. when the first forerunner symptoms appear - before the disease breaks out, is under consideration; indeed, the effectiveness of a treatment is possibly better if it is applied as early as possible in the pathological process.
• basic research in experimental models (cell cultures, mice) with a view to clarifying pathophysiological mechanisms and discovering new drug targets;
• clinical trials aimed at new treatments and - ultimately - at the prevention of schizophrenia.

Clinical research:

• Investigate other factors of vulnerability
• Study interactions between genes and environment
• Determine a reliable profile of biological markers for early detection and intervention
  
• Evaluate the profile of biomarkers in a longitudinal study, i.e. periodically and over several years following the first psychotic episodes

 Experimental models:

• Investigate pathophysiological mechanisms
• Study the imbalance of the "redox" system (system of reductions and oxidations in nerve cells) during critical phases of the development of the brain
  
• Study the role of the "redox" imbalance in the development of cells responsible for the formation of myelin, a substance which isolates and protects nerve fibres; these fibres connect the different sections of the brain with each other and transmit nerve impulses; the disorders regarding nerve fibres observed in patients account for their problems on the level of sensory, cognitive and motor integration.
• Extend this research to other psychiatric diseases such as bipolar disorders and autism, for which recent evidence shows the involvement of "redox" dysregulation; if this hypothesis is confirmed, it could have important consequences on the treatment of these diseases.
• Identify anomalies with regard to gene constellations involved in schizophrenia

 Clinical trials:

• Conduct trials with substances that raise the cerebral level of glutathione (precursors of glutathione, enzyme modifiers)

The research programme developed by the URS  should lead to a better understanding of the various disorders related to schizophrenia. It should make it possible to establish a profile of reliable biological markers for early detection of subjects at risk. A preventive treatment, without side effects, could then be administered to avoid irreversible damages of the nervous system during development.