Key role for lipids in cognitive symptoms of schizophrenia
In: ISSN: 2158-3188, 2020
Online
academicJournal
Zugriff:
International audience ; Schizophrenia (SZ) is a psychiatric disorder with a convoluted etiology that includes cognitive symptoms, which arise from among others a dysfunctional dorsolateral prefrontal cortex (dlPFC). In our search for the molecular underpinnings of the cognitive deficits in SZ, we here performed RNA sequencing of gray matter from the dlPFC of SZ patients and controls. We found that the differentially expressed RNAs were enriched for mRNAs involved in the Liver X Receptor/Retinoid X Receptor (LXR/RXR) lipid metabolism pathway. Components of the LXR/RXR pathway were upregulated in gray matter but not in white matter of SZ dlPFC. Intriguingly, an analysis for shared genetic etiology, using two SZ genome-wide association studies (GWASs) and GWAS data for 514 metabolites, revealed genetic overlap between SZ and acylcarnitines, VLDL lipids, and fatty acid metabolites, which are all linked to the LXR/RXR signaling pathway. Furthermore, analysis of structural T1-weighted magnetic resonance imaging in combination with cognitive behavioral data showed that the lipid content of dlPFC gray matter is lower in SZ patients than in controls and correlates with a tendency towards reduced accuracy in the dlPFC-dependent task-switching test. We conclude that aberrations in LXR/RXR-regulated lipid metabolism lead to a decreased lipid content in SZ dlPFC that correlates with reduced cognitive performance.
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Key role for lipids in cognitive symptoms of schizophrenia
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Autor/in / Beteiligte Person: | Maas, Dorien, A ; Martens, Marijn, B ; Priovoulos, Nikos ; Zuure, Wieteke, A ; Homberg, Judith, R ; Nait-Oumesmar, Brahim ; Martens, Gerard, J M ; Donders Institute for Brain, Cognition and Behaviour ; Radboud University Nijmegen ; Institut du Cerveau = Paris Brain Institute (ICM) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) ; Radboud University Medical Center Nijmegen ; NeuroDrug Research Ltd Nijmegen, The Netherlands ; Spinoza Centre for Neuroimaging Amsterdam, The Netherlands |
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Zeitschrift: | ISSN: 2158-3188, 2020 |
Veröffentlichung: | HAL CCSD ; Nature Pub. Group, 2020 |
Medientyp: | academicJournal |
DOI: | 10.1038/s41398-020-01084-x |
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