Investigating the association of the plasma lipidomic profile with cognitive performance and genetic risk in the PsyCourse study
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.
Authors
- Janos L. Kalman (ORCID: https://orcid.org/0000-0003-0930-4214)
- Jens Wiltfang (ORCID: https://orcid.org/0000-0003-1492-5330)
- Sabrina K. Schaupp (ORCID: https://orcid.org/0000-0002-2062-3585)
- Urs Heilbronner (ORCID: https://orcid.org/0000-0001-7135-762X)
- Georg Juckel (ORCID: https://orcid.org/0000-0001-9860-9620)
- Mojtaba Oraki Kohshour (ORCID: https://orcid.org/0000-0002-1357-2636)
- Thomas Joseph Vogl (ORCID: https://orcid.org/0000-0001-5218-1075)
- Sergi Papiol (ORCID: https://orcid.org/0000-0001-9366-8728)
- Maria Heilbronner (ORCID: https://orcid.org/0009-0000-8344-275X)
- Philipp Khaitovich (ORCID: https://orcid.org/0000-0002-4305-0054)
- Thomas G. Schulze (ORCID: https://orcid.org/0000-0001-6624-2975)
- Eva Christina Schulte (ORCID: https://orcid.org/0000-0003-3105-5672)
- Martin von Hagen
- Max Schmauß
- Monika Budde (ORCID: https://orcid.org/0000-0001-7301-9157)
- Udo Dannlowski (ORCID: https://orcid.org/0000-0002-0623-3759)
- Peter Falkai (ORCID: https://orcid.org/0000-0002-0284-2290)
- Eva Z. Reininghaus (ORCID: https://orcid.org/0000-0001-5964-4087)
- Daniela Reich‐Erkelenz (ORCID: https://orcid.org/0000-0001-7818-539X)
- Kristina Adorjan (ORCID: https://orcid.org/0000-0001-7501-9556)
- Carsten Spitzer (ORCID: https://orcid.org/0000-0002-2711-285X)
- Fanny Senner (ORCID: https://orcid.org/0000-0003-3375-5314)
- Anna Tkachev (ORCID: https://orcid.org/0000-0001-5653-6988)
- Elena Stekolshchikova
- Andreas J. Fallgatter
Institutions
- University of Bern (CH)
- Ahvaz Jundishapur University of Medical Sciences (IR)
- Skolkovo Institute of Science and Technology (RU)
- University of Bonn (DE)
- Johns Hopkins University (US)
- Medical University of Graz (AT)
- SUNY Upstate Medical University (US)
- University of Münster (DE)
- University Hospital Bonn (DE)
- Johns Hopkins Medicine (US)
- University Hospital of Bern (CH)
- German Center for Neurodegenerative Diseases (DE)
- LMU Klinikum (DE)
- Ravensburg University of Cooperative Education (DE)
- German Center for Infection Research (DE)
- Universitätsmedizin Göttingen (DE)
- German Centre for Cardiovascular Research (DE)
- Max Planck Institute of Psychiatry (DE)
- LWL-Universitätsklinikum Bochum (DE)
- German Center for Diabetes Research (DE)
- Bezirkskrankenhaus Augsburg (DE)
- University of Rostock (DE)
- University of Aveiro (PT)
- University of Tübingen (DE)
- Ludwig-Maximilians-Universität München (DE)
- Ruhr University Bochum (DE)
Publication Details
- Journal
- Translational Psychiatry
- Published
- 2025-03-28
- DOI
- https://doi.org/10.1038/s41398-025-03323-5
- Citations
- 2
- Primary Topic
- Liver Disease Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 2.71
Funders
- Deutsche Forschungsgemeinschaft
- Horizon 2020 Framework Programme
- Medizinischen Fakultät, Ludwig-Maximilians-Universität München