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Published Online: 11 June 2024

Association of Occupational Dysfunction and Hospital Admissions With Different Polygenic Profiles in Bipolar Disorder

Lina Jonsson, Ph.D. [email protected], Elin Hörbeck, M.D., Amedeo Primerano, M.D., Jie Song, Ph.D., Robert Karlsson, Ph.D., Erik Smedler, M.D., Ph.D., Katherine Gordon-Smith, Ph.D., Lisa Jones, Ph.D., Nicholas Craddock, M.D., Ph.D., Ian Jones, Ph.D., Patrick F. Sullivan, M.D., Ph.D., Erik Pålsson, Ph.D., Arianna Di Florio, M.D., Ph.D., Timea Sparding, Ph.D., and Mikael Landén, M.D., Ph.D.Authors Info & Affiliations
Publication: American Journal of Psychiatry
Volume 181, Number 7
https://doi.org/10.1176/appi.ajp.20230073
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Abstract

Objective:

Many but not all persons with bipolar disorder require hospital care because of severe mood episodes. Likewise, some but not all patients experience long-term occupational dysfunction that extends beyond acute mood episodes. It is not known whether these dissimilar outcomes of bipolar disorder are driven by different polygenic profiles. Here, polygenic scores (PGSs) for major psychiatric disorders and educational attainment were assessed for associations with occupational functioning and psychiatric hospital admissions in bipolar disorder.

Methods:

A total of 4,782 patients with bipolar disorder and 2,963 control subjects were genotyped and linked to Swedish national registers. Longitudinal measures from at least 10 years of registry data were used to derive percentage of years without employment, percentage of years with long-term sick leave, and mean number of psychiatric hospital admissions per year. Ordinal regression was used to test associations between outcomes and PGSs for bipolar disorder, schizophrenia, major depressive disorder, attention deficit hyperactivity disorder (ADHD), and educational attainment. Replication analyses of hospital admissions were conducted with data from the Bipolar Disorder Research Network cohort (N=4,219).

Results:

Long-term sick leave and unemployment in bipolar disorder were significantly associated with PGSs for schizophrenia, ADHD, major depressive disorder, and educational attainment, but not with the PGS for bipolar disorder. By contrast, the number of hospital admissions per year was associated with higher PGSs for bipolar disorder and schizophrenia, but not with the other PGSs.

Conclusions:

Bipolar disorder severity (indexed by hospital admissions) was associated with a different polygenic profile than long-term occupational dysfunction. These findings have clinical implications, suggesting that mitigating occupational dysfunction requires interventions other than those deployed to prevent mood episodes.

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Supplementary Material

File (appi.ajp.20230073.ds001.pdf)

Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Volume 181 • Number 7 • July 01, 2024
Pages: 620 - 629
PubMed: 38859703

History

Received: 26 January 2023
Revision received: 23 June 2023
Revision received: 30 August 2023
Accepted: 14 September 2023
Published online: 11 June 2024
Published in print: July 01, 2024

Keywords

  1. Attention Deficit Hyperactivity Disorder
  2. Bipolar Disorders
  3. Genetics/Genomics
  4. Occupational Functioning
  5. Polygenic Risk Scores
  6. Schizophrenia

Authors

Affiliations

Lina Jonsson, Ph.D. [email protected]
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Jonsson, Hörbeck, Smedler, Pålsson, Sparding, Landén); National Centre for Mental Health, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Primerano, Craddock, I. Jones, Di Florio); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Song, Karlsson, Sullivan, Landén); Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China (Song); Department of Psychological Medicine, University of Worcester, Worcester, U.K. (Gordon-Smith, L. Jones); Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill (Sullivan).
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Elin Hörbeck, M.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Jonsson, Hörbeck, Smedler, Pålsson, Sparding, Landén); National Centre for Mental Health, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Primerano, Craddock, I. Jones, Di Florio); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Song, Karlsson, Sullivan, Landén); Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China (Song); Department of Psychological Medicine, University of Worcester, Worcester, U.K. (Gordon-Smith, L. Jones); Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill (Sullivan).
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Amedeo Primerano, M.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Jonsson, Hörbeck, Smedler, Pålsson, Sparding, Landén); National Centre for Mental Health, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Primerano, Craddock, I. Jones, Di Florio); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Song, Karlsson, Sullivan, Landén); Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China (Song); Department of Psychological Medicine, University of Worcester, Worcester, U.K. (Gordon-Smith, L. Jones); Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill (Sullivan).
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Jie Song, Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Jonsson, Hörbeck, Smedler, Pålsson, Sparding, Landén); National Centre for Mental Health, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Primerano, Craddock, I. Jones, Di Florio); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Song, Karlsson, Sullivan, Landén); Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China (Song); Department of Psychological Medicine, University of Worcester, Worcester, U.K. (Gordon-Smith, L. Jones); Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill (Sullivan).
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Robert Karlsson, Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Jonsson, Hörbeck, Smedler, Pålsson, Sparding, Landén); National Centre for Mental Health, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Primerano, Craddock, I. Jones, Di Florio); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Song, Karlsson, Sullivan, Landén); Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China (Song); Department of Psychological Medicine, University of Worcester, Worcester, U.K. (Gordon-Smith, L. Jones); Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill (Sullivan).
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Erik Smedler, M.D., Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Jonsson, Hörbeck, Smedler, Pålsson, Sparding, Landén); National Centre for Mental Health, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Primerano, Craddock, I. Jones, Di Florio); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Song, Karlsson, Sullivan, Landén); Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China (Song); Department of Psychological Medicine, University of Worcester, Worcester, U.K. (Gordon-Smith, L. Jones); Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill (Sullivan).
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Katherine Gordon-Smith, Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Jonsson, Hörbeck, Smedler, Pålsson, Sparding, Landén); National Centre for Mental Health, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Primerano, Craddock, I. Jones, Di Florio); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Song, Karlsson, Sullivan, Landén); Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China (Song); Department of Psychological Medicine, University of Worcester, Worcester, U.K. (Gordon-Smith, L. Jones); Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill (Sullivan).
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Lisa Jones, Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Jonsson, Hörbeck, Smedler, Pålsson, Sparding, Landén); National Centre for Mental Health, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Primerano, Craddock, I. Jones, Di Florio); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Song, Karlsson, Sullivan, Landén); Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China (Song); Department of Psychological Medicine, University of Worcester, Worcester, U.K. (Gordon-Smith, L. Jones); Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill (Sullivan).
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Nicholas Craddock, M.D., Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Jonsson, Hörbeck, Smedler, Pålsson, Sparding, Landén); National Centre for Mental Health, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Primerano, Craddock, I. Jones, Di Florio); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Song, Karlsson, Sullivan, Landén); Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China (Song); Department of Psychological Medicine, University of Worcester, Worcester, U.K. (Gordon-Smith, L. Jones); Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill (Sullivan).
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Ian Jones, Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Jonsson, Hörbeck, Smedler, Pålsson, Sparding, Landén); National Centre for Mental Health, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Primerano, Craddock, I. Jones, Di Florio); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Song, Karlsson, Sullivan, Landén); Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China (Song); Department of Psychological Medicine, University of Worcester, Worcester, U.K. (Gordon-Smith, L. Jones); Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill (Sullivan).
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Patrick F. Sullivan, M.D., Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Jonsson, Hörbeck, Smedler, Pålsson, Sparding, Landén); National Centre for Mental Health, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Primerano, Craddock, I. Jones, Di Florio); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Song, Karlsson, Sullivan, Landén); Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China (Song); Department of Psychological Medicine, University of Worcester, Worcester, U.K. (Gordon-Smith, L. Jones); Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill (Sullivan).
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Erik Pålsson, Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Jonsson, Hörbeck, Smedler, Pålsson, Sparding, Landén); National Centre for Mental Health, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Primerano, Craddock, I. Jones, Di Florio); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Song, Karlsson, Sullivan, Landén); Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China (Song); Department of Psychological Medicine, University of Worcester, Worcester, U.K. (Gordon-Smith, L. Jones); Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill (Sullivan).
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Arianna Di Florio, M.D., Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Jonsson, Hörbeck, Smedler, Pålsson, Sparding, Landén); National Centre for Mental Health, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Primerano, Craddock, I. Jones, Di Florio); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Song, Karlsson, Sullivan, Landén); Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China (Song); Department of Psychological Medicine, University of Worcester, Worcester, U.K. (Gordon-Smith, L. Jones); Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill (Sullivan).
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Timea Sparding, Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Jonsson, Hörbeck, Smedler, Pålsson, Sparding, Landén); National Centre for Mental Health, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Primerano, Craddock, I. Jones, Di Florio); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Song, Karlsson, Sullivan, Landén); Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China (Song); Department of Psychological Medicine, University of Worcester, Worcester, U.K. (Gordon-Smith, L. Jones); Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill (Sullivan).
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Mikael Landén, M.D., Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Jonsson, Hörbeck, Smedler, Pålsson, Sparding, Landén); National Centre for Mental Health, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Primerano, Craddock, I. Jones, Di Florio); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Song, Karlsson, Sullivan, Landén); Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China (Song); Department of Psychological Medicine, University of Worcester, Worcester, U.K. (Gordon-Smith, L. Jones); Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill (Sullivan).
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Notes

Send correspondence to Dr. Jonsson ([email protected]).

Competing Interests

Dr. Ian Jones has received grant support from Akrivia Health and Takeda. Dr. Sullivan has served as a consultant for and is a shareholder in Neumora Therapeutics. Dr. Landén has received lecture honoraria from Lundbeck Pharmaceutical and has served as a consultant for AstraZeneca. The other authors report no financial relationships with commercial interests.

Funding Information

Funding support for the Swedish Bipolar Collection was provided by a grant from the Stanley Medical Research Institute to the Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard. Funding for this specific project was provided by the Swedish Research Council (2022-01643) and the Swedish Brain Foundation (FO2022-0217). Funding for the Bipolar Disorder Research Network was provided by the Wellcome Trust and Stanley Medical Research Institute. Dr. Jonsson was supported by a grant from the Swedish state under the ALF agreement (ALFGBG-966370) and a grant from Genomic Medicine Sweden (GMS K131050263). Dr. Smedler was supported by a grant from the Swedish state under the ALF agreement (ALFGBG-933732). Dr. Landén was supported by a grant from the Wenner-Gren Foundation (SSv2019-0008).

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