Dysregulated Lipid Metabolism Precedes Onset of Psychosis
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Background: A key clinical challenge in the management of individuals at clinical high risk for psychosis (CHR) is that it is difficult to predict their future clinical outcomes. Here, we investigated if the levels of circulating molecular lipids are related to adverse clinical outcomes in this group. Methods: Serum lipidomic analysis was performed in 263 CHR individuals and 51 healthy control subjects, who were then clinically monitored for up to 5 years. Machine learning was used to identify lipid profiles that discriminated between CHR and control subjects, and between subgroups of CHR subjects with distinct clinical outcomes. Results: At baseline, compared with control subjects, CHR subjects (independent of outcome) had higher levels of triacylglycerols with a low acyl carbon number and a double bond count, as well as higher levels of lipids in general. CHR subjects who subsequently developed psychosis (n = 50) were distinguished from those that did not (n = 213) on the basis of lipid profile at baseline using a model with an area under the receiver operating curve of 0.81 (95% confidence interval = 0.69–0.93). CHR subjects who became psychotic had lower levels of ether phospholipids than CHR individuals who did not (p <.01). Conclusions: Collectively, these data suggest that lipidomic abnormalities predate the onset of psychosis and that blood lipidomic measures may be useful in predicting which CHR individuals are most likely to develop psychosis.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Biological Psychiatry |
| Vol/bind | 89 |
| Udgave nummer | 3 |
| Sider (fra-til) | 288-297 |
| Antal sider | 10 |
| ISSN | 0006-3223 |
| DOI | |
| Status | Udgivet - 1 feb. 2021 |
Bibliografisk note
Funding Information:
This study has received funding from the European Union's Seventh Framework Programme for projects EU-GEI?European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (Grant No. HEALTH-F2-2010-241909 [to PMG, NB-V, MN, AR-R, SR, GS, RB, M-OK, GPA, LdH, and MvdG]) and METSY?Neuroimaging Platform for Characterization of Metabolic Comorbidities in Psychotic Disorders (Grant No. 602478 [to MO]). Additional support was provided by a Medical Research Council Fellowship (Grant No. MR/J008915/1 [to MJK]), Ministerio de Ciencia, Innovaci?n e Universidades (Grant No. PSI2017-87512-C2-1-R), and Generalitat de Catalunya (Grant No. 2017SGR1612 and ICREA Academia Award [to NB-V]). We thank Cecilia Carlsson for technical assistance in lipidomic analysis. We would also like to acknowledge the Turku Metabolomics Centre, which is a part of Biocentre Finland, for their role in this study. The lipidomics dataset and the relevant clinical metadata generated in this study are available from the EU-GEI management group on reasonable request. We also thank the following EU-GEI High Risk Study Group collaborators: Maria Calem, Stefania Tognin, Gemma Modino, Tamar C. Kraan, Daniella S. van Dam, Nadine Burger, Barnaby Nelson, Patrick McGorry, Christos Pantelis, Athena Politis, Joanne Goodall, Stefan Borgwardt, Charlotte Rapp, Sarah Ittig, Erich Studerus, Renata Smieskova, Ary Gadelha, Elisa Brietzke, Graccielle Asevedo, Elson Asevedo, Andre Zugman, Tecelli Dom?nguez-Mart?nez, Anna Racciopi, Thomas R. Kwapil, Manel Monsonet, Araceli Rosa, Ariel Frajerman, Boris Chaumette, Julie Bourgin, Oussama Kebir, C?lia Jantac, Dorte Nordholm, Lasse Randers, Kristine Krakauer, Louise Glenth?j, Birte Glenth?j, Dominika Gebhard, Julia Arnhold, Joachim Klosterk?tter, Iris Lasser, Bernadette Winklbaur, Philippe A. Delespaul, Bart P. Rutten, and Jim van Os. The authors report no biomedical financial interests or potential conflicts of interest.
Funding Information:
This study has received funding from the European Union’s Seventh Framework Programme for projects EU-GEI—European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (Grant No. HEALTH-F2-2010-241909 [to PMG, NB-V, MN, AR-R, SR, GS, RB, M-OK, GPA, LdH, and MvdG]) and METSY—Neuroimaging Platform for Characterization of Metabolic Comorbidities in Psychotic Disorders (Grant No. 602478 [to MO]). Additional support was provided by a Medical Research Council Fellowship (Grant No. MR/J008915/1 [to MJK]), Ministerio de Ciencia, Innovación e Universidades (Grant No. PSI2017-87512-C2-1-R ), and Generalitat de Catalunya (Grant No. 2017SGR1612 and ICREA Academia Award [to NB-V]).
Publisher Copyright:
© 2020 Society of Biological Psychiatry
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