Linking lipid metabolism

Researchers to study how lipid metabolism links psychotic disorders, metabolic co-morbidities

Kelsey Kaustinen
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LASKUT, Finland—A new European Union (EU) project has been announced in which several research and industry partners will seek to develop and apply neuroimaging and bioinformatics tools to analyze lipid metabolism and its role as a common pathogenic link between psychotic disorders and metabolic co-morbidities, such as metabolic syndrome and diabetes. The hope is to identify and evaluate multimodal blood and neuroimaging markers that could aid in the diagnosis, prediction and monitoring of psychotic disorders and their related metabolic co-morbidities.
The project is slated to run four years, and will be coordinated by Research Professor Matej Oresic of the not-for-profit organization VTT Technical Research Centre of Finland. The project will have a total budget of €5.94 million (approximately $8.2 million), with the EU responsible for €4.23 million (approximately $5.8 million). In addition to VTT, other partners on the project include Biomax Informatics AG, Servicio Madrileño de Salud, University of Turku, National Institute for Health and Welfare of Finland, Philips Research and King’s College London. The partners hail from Finland, Spain, Germany and the United Kingdom, and include researchers and industry partners specializing in metabolic research, psychiatry, neuroimaging, bioinformatics and systems biology.
As noted on the EU website, the specific aims of this initiative are threefold: to “optimize a multidisciplinary approach for combining positron emission tomography (PET) and magnetic resonance imaging (MRI) with metabolomics approaches, develop a PET-method for exploring endocannabinoid pathways in early psychosis in longitudinal study setting and develop combined PET-MRI biomarker methodology for psychiatric disorders by studying neurotransmitter interactions with multiple PET scan and MRI sequences.”
Oresic has previously examined this relationship, authoring a review article titled “Obesity and psychotic disorders: uncovering common mechanisms through metabolomics” that appeared in Disease Models & Mechanisms in September 2012. The abstract of the article notes that “Primary obesity and psychotic disorders are similar with respect to the associated changes in energy balance and co-morbidities, including metabolic syndrome. Such similarities do not necessarily demonstrate causal links, but instead suggest that specific causes of and metabolic disturbances associated with obesity play a pathogenic role in the development of co-morbid disorders, potentially even before obesity develops.”
In addition, Oresic goes on to note that “A confounding issue is that the use of antipsychotic drugs, especially second-generation drugs, has been consistently associated with weight gain, insulin resistance and development of metabolic syndrome. For example, after only six months of treatment with some second-generation antipsychotics, the percentage of previously drug-naïve, first-episode adolescent patients who are at risk of developing metabolic syndrome rises from 17 percent to 40 percent. Kaddurah-Daouk, et al., examined the effects of antipsychotic medication on the serum lipidome, and found significant changes in lipid metabolism after just two to three weeks. In line with these findings, gene expression studies found that antipsychotics strongly activate genes involved in lipid homeostasis. This suggests that these psychotropic drugs target central nervous system neurons that also regulate mechanisms controlling energy balance and associated metabolic alterations.”
However, Oresic adds in the paper that additional research has also shown that “metabolic disruptions occur in individuals with psychotic disorders independently of drug effects. Studies from the pre-antipsychotic era of people with schizophrenia showed that the prevalence of diabetes or glucose intolerance was higher in patients than in controls.”
This is one of two neurologically focused partnerships VTT has entered into in recent months. On Sept. 18, VTT announced a collaboration with Florida Hospital Neuroscience Institute to evaluate the screening, diagnostic and prognostic potential of a biomarker assay for Alzheimer’s disease. The assay is the result of recent work by scientists from VTT and the University of Eastern Finland to discover a serum biochemical signature that can predict a patient’s progression to Alzheimer’s disease.

Kelsey Kaustinen

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