Investigating the association of the plasma lipidomic profile with cognitive performance and genetic risk in the PsyCourse study
Year: 2025
Type: article
Study design: Observational Study
Abstract: Although lipid biology may play a key role in the pathophysiology of mental health disorders such as schizophrenia (SCZ) and bipolar disorder (BD), the nature of this interplay and how it could shape phenotypic presentation, including cognitive performance is still incompletely understood. To address this question, we analyzed the association of plasma level of different lipid species with cognitive performance in the transdiagnostic PsyCourse Study. Plasma lipidomic profiles of 623 individuals (188 SCZ, 243 BD, 192 healthy controls) belonging to the PsyCourse Study were assessed using liquid chromatography and untargeted mass spectrometry. The association between 364 annotated lipid species from 16 lipid classes and six cognitive tests was evaluated. Likewise, the association of polygenic risk scores (PRS) for SCZ, BD, executive function (EF), and educational attainment (EA) with lipid plasma levels were also investigated. In the regression analysis, three lipid species belonging to phosphatidylethanolamine plasmalogen and one belonging to ceramide class showed significant negative association with Digit-Symbol test scores. Lipid class-based enrichment analysis in LipidR replicated the significance of the phosphatidylethanolamines class for the Digit-Symbol test, which evaluates the processing speed in cognitive tasks. Polygenic load for SCZ, BD, EF, or EA was not associated with lipid levels. Our findings suggest a link between lipids and cognitive performance independent of mental health disorders. Still, independent replication is warranted to better understand if phosphatidylethanolamines could represent an actionable pharmacologic target to tackle cognitive dysfunction, an important unmet clinical need that affects long-term functional outcomes in individuals with severe mental health disorders.
Source: Translational Psychiatry
Authors: Mojtaba Oraki Kohshour, Sergi Papiol, Anna Tkachev, Elena Stekolshchikova, Kristina Adorjan, Monika Budde, Urs Heilbronner, Maria Heilbronner, Janos L. Kalman, Daniela Reich-Erkelenz, Sabrina K. Schaupp, Fanny Senner, Thomas Vogl, Jens Wiltfang, Eva Z. Reininghaus, Georg Juckel, Udo Dannlowski, Andreas J. Fallgatter, Carsten Spitzer, Max Schmauß, Martin von Hagen, Peter Falkai, Philipp Khaitovich, Thomas G. Schulze, Eva C. Schulte
Institutions: Ahvaz Jundishapur University of Medical Sciences, LMU Klinikum, Institut für Psychiatrische Phänomik und Genomik, Ludwig-Maximilians-Universität München, Max Planck Institute of Psychiatry, Skolkovo Institute of Science and Technology, University of Bern, Zentrum für Psychiatrie Südwürttemberg, German Center for Neurodegenerative Diseases, Universitätsmedizin Göttingen, University of Aveiro, University of Göttingen, Medical University of Graz, LWL-Universitätsklinikum Bochum, Ruhr University Bochum, University of Münster, Deutsches Zentrum für Psychische Gesundheit, University of Tübingen, Universitätsmedizin Rostock, University of Rostock, University of Augsburg, Bezirkskrankenhaus Augsburg, Johns Hopkins University, SUNY Upstate Medical University, Johns Hopkins Medicine, University of Bonn, University Hospital Bonn
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,290
Awards: G1392250549, G1527371574, G179444772, G214923873, G222496000, G238323396, G2511155013, G2579491456, G2831939486, G3374514668, G3879576984, A New Intervention for Implementation of Pharmacogenetics in Psychiatry, G4812287033, G5275296542, Longitudinale Veränderungen der Gesamtheit kleiner RNAs in der transdiagnostinschen PsyCourse Studie, DZPG Aufbauförderung - 'Standort München': Betriebskonzept, G648958512, G6733821374, G7341669135, G8087705, G8377545079, G961545024
OpenAlex ID: W4408969148