Polygenic scores for executive functioning as predictors of performance improvements after repeated testing in major psychiatric disorders
Year: 2026
Type: article
Study design: Observational Study
Abstract: Executive Functions (EF) control goal-oriented behaviors and are disrupted in patients with psychiatric disorders (PPD). Repeated EF testing in clinical practice and research aims to evaluate disease progression and treatment efficacy. Performance improvements (or “practice effects”) are expected, while deficiencies had been proposed as markers of conversion to dementia. Given the high conversion risk in PPD, understanding the determinants of practice effects is of high relevance. However, the role of genetic predisposition remains unknown. We aim to test the influence of polygenic scores on practice effects across PPD. Data were drawn from the longitudinal deep-phenotyping PsyCourse Study (N = 1,558). Latent factor analysis revealed a common Executive Function factor (cEF), which explained shared variability of 5 different EF tests. We tested the association of polygenic scores for the cEF (PGS-cEF) – based on the largest GWAS on cEF to date (N = 427,037) - with cEF scores improvements in PsyCourse. The PGS for general psychopathology “p-Factor” (PGS-PF) were used as a psychiatric liability comparison. Volunteer adults (> 18 y.o.), with and without diagnoses within the Affective-Psychotic spectrum were recruited across Germany and Austria, followed-up four times at six months intervals. The mean PGS-cEF was lower in patients with psychotic vs. affective disorders (diff: -0.01, 95% CI -0.02 to -0.002) and controls (diff: -0.02, 95% CI -0.03 - -0.006); while the mean PGS-PF was higher in psychotic vs. affective disorders (diff: 0.02, 95% CI 0.01 to 0.04) and controls (diff: 0.03, 95% CI 0.02–0.05). Overall, the PGS-cEF x Visit interaction was associated with the phenotypic latent cEF scores (eta2 = 0.03; p = 1.32e-15), but not with the scores of individual EF tests. There was no PGS-PF x Visit interaction associated with any cognitive score. To the best of our knowledge, this is the first analysis of genetic factors related to EF improvements in PPD. The PGS-cEF, but not the PGS-PF predicted practice effects in cEF scores over 18 months. This prediction was only observable using the latent‑cEF level, and not with the individual scores. Genetic testing and deep phenotyping might hint further information about EF vulnerability in PPD.
Source: Scientific Reports
Authors: Alba Navarro-Flores, Maria Heilbronner, Hajar Rafiee, Bernadette Wendel, Sergi Papiol, Kristina Adorjan, Monika Budde, Mojtaba Oraki Kohshour, Eva C. Schulte, Daniela Reich-Erkelenz, Fanny Senner, Ion-George Anghelescu, Volker Arolt, Bernhard T. Baune, Udo Dannlowski, Detlef E. Dietrich, Andreas J. Fallgatter, Christian Figge, Fabian U. Lang, Georg Juckel, Carsten Konrad, Jens Reimer, Eva Z. Reininghaus, Max Schmauß, Andrea Schmitt, Carsten Spitzer, Jens Wiltfang, Jörg Zimmermann, Peter Falkai, Thomas G. Schulze, Urs Heilbronner
Institutions: Institut für Psychiatrische Phänomik und Genomik, Ludwig-Maximilians-Universität München, University of Padua, Universitätsmedizin Göttingen, University of Göttingen, Max Planck Institute of Psychiatry, University of Bern, Ahvaz Jundishapur University of Medical Sciences, University of Bonn, University Hospital Bonn, LMU Klinikum, Deutsches Zentrum für Psychische Gesundheit, Zentrum für Psychiatrie Südwürttemberg, University of Münster, The University of Melbourne, Florey Institute of Neuroscience and Mental Health, Bielefeld University, Medizinische Hochschule Hannover, University of Tübingen, Universität Ulm, LWL-Universitätsklinikum Bochum, Ruhr University Bochum, Agaplesion Diakonieklinikum Rotenburg, Klinikum Itzehoe, University Medical Center Hamburg-Eppendorf, Medical University of Graz, University of Augsburg, Bezirkskrankenhaus Augsburg, Universidade de São Paulo, Universitätsmedizin Rostock, University of Rostock, German Center for Neurodegenerative Diseases, University of Aveiro, Johns Hopkins University, SUNY Upstate Medical University, Johns Hopkins Medicine
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W7136367588