Dysregulated Lipid Metabolism Precedes Onset of Psychosis
Alex M. Dickens, Partho Sen, Matthew J. Kempton, Neus Barrantes‐Vidal, Conrad Iyegbe, Merete Nordentoft, Thomas Pollak, Anita Riecher‐Rössler, Stephan Ruhrmann, Gabriele Sachs, Rodrigo A. Bressan, Marie‐Odile Krebs, G. Paul Amminger, Lieuwe de Haan, Mark van der Gaag, Lucia Valmaggia, Tuulia Hyötyläinen, Philip McGuire, Lucia Valmaggia, Matthew J. Kempton, Maria Calem, Stefania Tognin, Gemma Modinos, Lieuwe de Haan, Mark van der Gaag, Eva Velthorst, Tamar Kraan, Daniëlla S. van Dam, Nadine Burger, Barnaby Nelson, Patrick D. McGorry, G. Paul Amminger, Christos Pantelis, Athena Politis, Joanne Goodall, Anita Riecher‐Rössler, Stefan Borgwardt, Charlotte Rapp, Sarah Ittig, Erich Studerus, Renata Smieskova, Rodrigo A. Bressan, Ary Gadelha, Elisa Brietzke, Graccielle Asevedo, Elson Asevedo, André Zugman, Neus Barrantes‐Vidal, Tecelli Domínguez‐Martínez, Anna Racciopi, Thomas R. Kwapil, Manel Monsonet, Araceli Rosa, Ariel Frajerman, Boris Chaumette, Julie Bourgin, Oussama Kébir, Célia Jantac, Marie‐Odile Krebs, Dorte Nordholm, Lasse Randers, Kristine Krakauer, Louise Birkedal Glenthøj, Birte Glenthøj, Merete Nordentoft, Stephan Ruhrmann, Dominika Gebhard, Julia Arnhold, Joachim Klosterkötter, Gabriele Sachs, Iris Lasser, Bernadette Winklbaur, Philippe Delespaul, Bart P. F. Rutten, Jim van Os, Matej Orešič, Philip McGuire
Abstract
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.