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METSY Consortium to Develop Neuroimaging, Bioinformatics Tools for Psychosis Biomarker Studies


This article has been updated to include comments from Biomax Informatics about its participation in the consortium.

A newly launched European consortium studying links between lipid metabolism, psychotic disorders, and metabolic co-morbidities such as metabolic syndrome and diabetes will also develop neuroimaging and bioinformatics tools to locate possible diagnostic biomarkers of psychosis.

The so-called METSY consortium is funded in part by the EU's Seventh Framework Programme, which has provided about €4.23 million ($5.65 million) of the €5.94 million total project budget. The rest of the funds will come from the consortium's members which are the VTT Technical Research Center of Finland, University of Turku, Finland's National Institute for Health and Welfare, Biomax Informatics, the Madrid Health Service, Philips Research, and Kings College London.

Over the next four years, members will identify and evaluate multi-modal blood and neuroimaging biomarkers that could be used to predict and monitor psychotic disorders like schizophrenia and associated disorders like obesity and cardiovascular disease.

They'll use techniques such as magnetic resonance imaging, position emission tomography, and metabolite profiling to generate imaging and metabolomic data from samples collected from about 500 patients recruited at four sites in Spain, the UK, and Finland, Matej Orešič, consortium coordinator and research professor at VTT, told BioInform. A central repository developed and maintained by consortium members in Spain will house image data collected from multiple sites so it can be made available to other members, he said.

The consortium will also develop software that uses a combination of metabolic, imaging, and clinical data to predict patient outcomes. For this portion of the project, Orešič said that Philips Research is developing tools that can combine images from MRIs and PET scans. Other consortium members are working on tools that can extract information from these combined images and integrate them with metabolic, clinical, and cognitive variables using statistical and network-based methods.

"We have … a decision support system that takes the data, like metabolic variables and image variables and basically develops a map" that provides a visual representation of psychosis-related changes, Orešič said.

Meanwhile, Biomax Informatics will work on building a semantic knowledgebase for the consortium using image data and molecular pathways identified in the various psychosis studies, he said.

In an email, Dieter Maier, Biomax's head of project management, told BioInform that company will use its BioXM Knowledge Management Environment and its BioRS Integration and Retrieval System to "integrate existing knowledge sources about brain structure and function, extend them with literature-derived information about psychosis and genetic factors and combine that with the clinical, imaging and metabolic data generated within the METSY project."

This will produce "a semantic network of psychosis specific knowledge based on associations between structures, functions, and molecules ... which can be overlaid with the patient specific data" and analysed with algorithms developed by the consortium, he said.

The METSY members plan to use the software they develop to explore structural and metabolic changes that occur in the brain during psychotic episodes. They'll also analyze changes in participants' metabolic profiles to better understand how alterations at the metabolite level play a part in the rise of associated conditions like diabetes — an aspect of psychosis that is both "well known" and "poorly understood," according to Orešič.

Co-diseases are in part linked to the use of antipsychotics which have been implicated in cases of metabolic syndrome, for instance; however, studies show that there may also be an "underlying pathogenic link" involved, he said.

This potential link has been documented in studies like this one in Genome Medicine which found, based on the analysis of serum samples from 139 subjects with psychotic disorders, that "specific metabolic abnormalities related to glucoregulatory processes and proline metabolism are specifically associated with schizophrenia and reflect two different disease-related pathways." A second study, also in Genome Medicine, analyzed the roles of phospholipids and insulin resistance in schizophrenia with data from 19 twin pairs and concluded that "altered neurotransmission in schizophrenia may be in part mediated by reactive lipids such as prostaglandins."

Findings like these are why the group is now trying to "link this imaging approach commonly used in psychotic research … to metabolic research," Orešič explained. "That way we can get a better insight into this underlying link that could be then explored more diagnostically [and could] also [provide] some clues about the etiology of the psychotic disorders."

One line of research they'll explore as part of the METSY project is the role that the endocannabinoid system — a group of neuromodulatory lipids and receptors that are involved in physiological processes such as mood and memory — plays in psychosis. "[We will use] PET imaging to really look at the distribution of these endocannabinoids and receptors," Orešič said. "And that will then be linked to characterization[s] of endocannabinoid metabolites in psychosis."