Abstract
BackgroundPsychotic patients are at high risk for developing obesity, metabolic syndrome and type 2 diabetes. These metabolic co-morbidities are hypothesized to be related to both treatment side-effects as well as to metabolic changes occurring during the psychosis. Earlier metabolomics studies have shown that blood metabolite levels are predictive of insulin resistance and type 2 diabetes in the general population as well as sensitive to the effects of antipsychotics. Here we aimed to identify the metabolite profiles predicting future weight gain and other metabolic abnormalities in psychotic patients.MethodsWe applied metabolomics to investigate serum metabolite profiles in a prospective study setting in 36 first-episode psychosis patients during the first year of the antipsychotic treatment and 19 controls. Two analytical platforms with broad analytical coverage were used. Molecular lipids were analysed by ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC_QTOFMS) and polar metabolites were analysed by two-dimensional gas chromatography coupled to TOFMS (GCxGC-TOFMS). Ongoing prospective metabolomics studies ae focusing on the subjects in at-risk mental state.ResultsWhile corroborating several earlier findings when comparing cases and controls and the effects of the antipsychotic medication, we also found that prospective weight gain in psychotic patients was associated with increased levels of triacylglycerols with low carbon number and double-bond count at baseline and independent of obesity, that is, lipids known to be associated with increased liver fat.DiscussionThe first-episode psychotic patients who rapidly gain weight in the follow-up have early metabolic disturbances which are associated with insulin resistance and fatty liver. Our studies suggest that metabolite profiles may be used to identify the psychotic patients most vulnerable to develop metabolic co-morbidities, and may point to a pharmacological approach to counteract the antipsychotic-induced weight gain.
Highlights
Psychotic patients are at high risk for developing obesity, metabolic syndrome and type 2 diabetes
Molecular lipids were analysed by ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC_QTOFMS) and polar metabolites were analysed by two-dimensional gas chromatography coupled to TOFMS (GCxGC-TOFMS)
While corroborating several earlier findings when comparing cases and controls and the effects of the antipsychotic medication, we found that prospective weight gain in psychotic patients was associated with increased levels of triacylglycerols with low carbon number and double-bond count at baseline and independent of obesity, that is, lipids known to be associated with increased liver fat
Summary
S69 psychosis is presented and compared with matched healthy controls. Three time points (baseline, 2 months, 12 months) are available for patients and two (baseline, 12 month) for controls. First results regarding the gut microbiome will be presented (Schwarz et al 2017), and the possible contribution of gut microbiota to inflammation and weight gain in first-episode psychosis explored. Results: Our previous findings from a subset of the study sample found most marked changes in innate immunity chemokines (Mäntylä et al 2015), whereas full longitudinal data on 38 cyto- and chemokines will be available at the SIRS congress. As a preliminary result on the longitudinal course of inflammation, high-sensitivity C-reactive protein showed a significant increase during the first year of treatment in patients (median baseline 0.65 mg/l, 2 months 0.79 mg/l and 12 months 1.68 mg/l). Discussion: The findings will be discussed in the context of to what extent they may reflect underlying disease mechanisms and environmental contributions, including gut microbiota alterations, and to what extent inflammation is a secondary phenomenon related to antipsychotic use and weight gain.
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