Contrasting genetic burden for bipolar disorder: Early onset versus late onset in an older adult bipolar disorder sample
Older Adults with Bipolar Disorder (OABD) represent a heterogeneous group, including those with early and late onset of the disorder. Recent evidence shows both groups have distinct clinical, cognitive, and medical features, tied to different neurobiological profiles. This study explored the link between polygenic risk scores (PRS) for bipolar disorder (PRS-BD), schizophrenia (PRS-SCZ), and major depressive disorder (PRS-MDD) with age of onset in OABD. PRS-SCZ, PRS-BD, and PRS-MDD among early vs late onset were calculated. PRS was used to infer posterior SNP effect sizes using a fully Bayesian approach. Demographic, clinical, and cognitive variables were also analyzed. Logistic regression analysis was used to estimate the amount of variation of each group explained by standardized PRS-SCZ, PRS-MDD, and PRS-BD. A total of 207 OABD subjects were included (144 EOBD; 63 LOBD). EOBD showed higher PRS-BD compared to LOBD (p = 0.005), while no association was found between age of onset and PRS-SCZ or PRS-MDD. Compared to LOBD, EOBD individuals also showed a higher likelihood for suicide attempts (p = 0.01), higher presence of psychotic symptoms (p = 0.003), higher prevalence of BD-I (p = 0.002), higher rates of familiarity for any psychiatric disorder (p = 0.004), and lower processing speed measured with Trail-Making Test part A (p = 0.03). OABD subjects with an early onset showed a greater genetic burden for BD compared to subjects with a late onset. These findings contribute to the notion that EOBD and LOBD may represent different forms of OABD, particularly regarding the genetic predisposition to BD.
Authors
- Janos L. Kalman (ORCID: https://orcid.org/0000-0003-0930-4214)
- Ion‐George Anghelescu (ORCID: https://orcid.org/0000-0003-3130-6347)
- 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)
- Laura Montejo (ORCID: https://orcid.org/0000-0003-4407-9454)
- Mojtaba Oraki Kohshour (ORCID: https://orcid.org/0000-0002-1357-2636)
- Anabel Martínez‐Arán (ORCID: https://orcid.org/0000-0002-0623-6263)
- Carsten Konrad (ORCID: https://orcid.org/0000-0001-7015-3860)
- 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)
- Giovanna Fico (ORCID: https://orcid.org/0000-0003-1785-7126)
- Eva Christina Schulte (ORCID: https://orcid.org/0000-0003-3105-5672)
- Jörg Zimmermann (ORCID: https://orcid.org/0000-0002-7667-5616)
- Max Schmauß
- Monika Budde (ORCID: https://orcid.org/0000-0001-7301-9157)
- Eduard Vieta (ORCID: https://orcid.org/0000-0002-0548-0053)
- Bernhardt T. Baune
- Udo Dannlowski (ORCID: https://orcid.org/0000-0002-0623-3759)
- Vincenzo Oliva (ORCID: https://orcid.org/0000-0002-5961-6032)
- Andreas J. Fallgatter (ORCID: https://orcid.org/0000-0001-7713-4259)
- Michele De Prisco (ORCID: https://orcid.org/0000-0002-2032-1181)
- Peter Falkai (ORCID: https://orcid.org/0000-0002-0284-2290)
- Detlef E. Dietrich (ORCID: https://orcid.org/0000-0002-1159-6538)
- Brisa Solé (ORCID: https://orcid.org/0000-0003-1673-8248)
- Volker Arolt (ORCID: https://orcid.org/0000-0002-2445-9778)
- Eva Z. Reininghaus (ORCID: https://orcid.org/0000-0001-5964-4087)
- Carla Torrent (ORCID: https://orcid.org/0000-0003-0335-582X)
- Daniela Reich‐Erkelenz (ORCID: https://orcid.org/0000-0001-7818-539X)
- Kristina Adorjan (ORCID: https://orcid.org/0000-0001-7501-9556)
- Jens Reimer (ORCID: https://orcid.org/0009-0007-5406-5319)
- Christian Figge
- Fanny Senner (ORCID: https://orcid.org/0000-0003-3375-5314)
- Sara Martin‐Parra
- Andrea Ruíz
- Thomas G. Schulze
Institutions
- Ahvaz Jundishapur University of Medical Sciences (IR)
- Johns Hopkins University (US)
- University of Hildesheim (DE)
- Universität Hamburg (DE)
- The University of Melbourne (AU)
- Medical University of Graz (AT)
- SUNY Upstate Medical University (US)
- University of Münster (DE)
- Florey Institute of Neuroscience and Mental Health (AU)
- University Hospital Bonn (DE)
- University Hospital of Bern (CH)
- LMU Klinikum (DE)
- Medizinische Hochschule Hannover (DE)
- Centro de Investigación Biomédica en Red de Salud Mental (ES)
- Landwirtschaftskammer Niedersachsen (DE)
- Klinikum Itzehoe (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- European Neuroscience Institute Göttingen (DE)
- Bernstein Center for Computational Neuroscience Tübingen (DE)
- Max Planck Institute of Psychiatry (DE)
- LWL-Universitätsklinikum Bochum (DE)
- Fundació Clínic per a la Recerca Biomèdica (ES)
- Agaplesion Diakonieklinikum Rotenburg (DE)
- Bezirkskrankenhaus Augsburg (DE)
- Universitat de Barcelona (ES)
- University of Tübingen (DE)
- Ludwig-Maximilians-Universität München (DE)
- Ruhr University Bochum (DE)
Publication Details
- Journal
- European Neuropsychopharmacology
- Published
- 2024-12-22
- DOI
- https://doi.org/10.1016/j.euroneuro.2024.12.001
- Citations
- 4
- Primary Topic
- Bipolar Disorder and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.54
Funders
- Ministerio de Ciencia, Innovación y Universidades
- Centres de Recerca de Catalunya
- European Commission
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Generalitat de Catalunya
- Ministerio de Ciencia e Innovación
- Instituto de Salud Carlos III
- European Regional Development Fund