BJRP 011003

Glutathione / Redox dysregulation : towards a biomaker profile for early intervention in psychosis, a Brazil – Swiss consortium (BRASWISZ)

Abstract

Intervention in early psychosis (EP) has become a major domain of clinical development and research, but the benefits of these new treatment strategies are still hampered by a lack of evidence based knowledge regarding neurobiological mechanisms involved in the illness process. Identification of biomarkers for psychosis or for its various forms and identifications of new and more specific targets for medication are therefore important issues to be resolved. Research conducted in our laboratories has led to the development of the hypothesis that a genetically mediated glutathione/redox antioxidant dysregulation is a vulnerability factor, contributing to the development of schizophrenia.  Such redox dysregulation combined with environmental stressors at specific developmental stages could underlie structural and functional connectivity anomalies. The development of new research resources and strategies in the area of psychotic disorders is of very high priority for medical policy and regulation worldwide. Indeed, psychotic disorders represent an enormous cost to the society and their diagnosis, prevention, and treatment, however, are not as well developed as in somatic medicine.
Based on new etio-pathophysiological mechanisms, the BRASWISZ consortium aims to identify sensitive and accurate biomarker profiles for early diagnosis and monitoring the effectiveness of drugs. In early psychosis, schizophrenia and bipolar patients, we will evaluate biological correlates with advanced technologies such as brain imaging (MRS, DSI, PET), EEG as well as genetic, metabolic and inflammatory profiling Patients psychopathology and cognitive functioning will also be assessed in order to explore possible correlations between neurobiological characteristics and clinical manifestations of the illness or diagnostic subgroups.

The proposal will allow us to identify biomarker profiles useful for diagnosis and monitoring the effectiveness of drugs. Such a biomarker profile would be highly valuable in terms of (i) contributing to and improving the specificity of early identification of patients at risk to develop psychosis and as a consequence contributing to the development of preventive strategies in the handling of psychotic disorders; (ii) improving our capacity to discriminate diagnostic subgroups of patients if this profile is specific to certain subtypes of psychoses and as a consequence allowing more specific treatments; (iii) allowing a monitoring of treatment response if variations in the marker profile can be observed in the context  of changes in symptomatology; (iv) identification of new targets for medication in the pre-symptomatic and early phase of illness, and (v) provide a means for evaluation of efficacy of new treatments. Moreover, Brazil and Switzerland are very different in terms of economic and social development. Thus, we expect to identify different prevalence for risk factors correlated with psychotic disorders. By studying different groups with psychotic disorders and comparing them with controls and developed/developing country groups, we might be able to uncover biomarkers that would not be clear in a single population. Our work will also extend research in psychotic disorders to the full range of ethnic groups and socio-economic status.

Dr Kim DO

Dr Marco Aurelio ROMANO-SILVA