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Associations between patterns in comorbid diagnostic trajectories of individuals with schizophrenia and etiological factors

Author

Listed:
  • Morten Dybdahl Krebs

    (Mental Health Services Capital Region of Denmark
    iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research)

  • Gonçalo Espregueira Themudo

    (Mental Health Services Capital Region of Denmark
    iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research)

  • Michael Eriksen Benros

    (Copenhagen University Hospital
    University of Copenhagen)

  • Ole Mors

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Aarhus University Hospital)

  • Anders D. Børglum

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Aarhus University
    Aarhus University)

  • David Hougaard

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Statens Serum Institut)

  • Preben Bo Mortensen

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Aarhus University
    Aarhus University, Business and Social Sciences)

  • Merete Nordentoft

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Copenhagen University Hospital)

  • Michael J. Gandal

    (University of California, Los Angeles
    University of California, Los Angeles
    University of California, Los Angeles)

  • Chun Chieh Fan

    (Mental Health Services Capital Region of Denmark
    iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    University of California)

  • Daniel H. Geschwind

    (University of California, Los Angeles
    University of California, Los Angeles
    University of California, Los Angeles
    University of California Los Angeles)

  • Andrew J. Schork

    (Mental Health Services Capital Region of Denmark
    iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    The Translational Genomics Research Institute (TGEN))

  • Thomas Werge

    (Mental Health Services Capital Region of Denmark
    iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    University of Copenhagen
    University of Copenhagen)

  • Wesley K. Thompson

    (Mental Health Services Capital Region of Denmark
    iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    University of California)

Abstract

Schizophrenia is a heterogeneous disorder, exhibiting variability in presentation and outcomes that complicate treatment and recovery. To explore this heterogeneity, we leverage the comprehensive Danish health registries to conduct a prospective, longitudinal study from birth of 5432 individuals who would ultimately be diagnosed with schizophrenia, building individual trajectories that represent sequences of comorbid diagnoses, and describing patterns in the individual-level variability. We show that psychiatric comorbidity is prevalent among individuals with schizophrenia (82%) and multi-morbidity occur more frequently in specific, time-ordered pairs. Three latent factors capture 79% of variation in longitudinal comorbidity and broadly relate to the number of co-occurring diagnoses, the presence of child versus adult comorbidities and substance abuse. Clustering of the factor scores revealed five stable clusters of individuals, associated with specific risk factors and outcomes. The presentation and course of schizophrenia may be associated with heterogeneity in etiological factors including family history of mental disorders.

Suggested Citation

  • Morten Dybdahl Krebs & Gonçalo Espregueira Themudo & Michael Eriksen Benros & Ole Mors & Anders D. Børglum & David Hougaard & Preben Bo Mortensen & Merete Nordentoft & Michael J. Gandal & Chun Chieh F, 2021. "Associations between patterns in comorbid diagnostic trajectories of individuals with schizophrenia and etiological factors," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26903-7
    DOI: 10.1038/s41467-021-26903-7
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    1. Oleksandr Frei & Dominic Holland & Olav B. Smeland & Alexey A. Shadrin & Chun Chieh Fan & Steffen Maeland & Kevin S. O’Connell & Yunpeng Wang & Srdjan Djurovic & Wesley K. Thompson & Ole A. Andreassen, 2019. "Bivariate causal mixture model quantifies polygenic overlap between complex traits beyond genetic correlation," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    2. Matthias Studer & Gilbert Ritschard, 2016. "What matters in differences between life trajectories: a comparative review of sequence dissimilarity measures," Journal of the Royal Statistical Society Series A, Royal Statistical Society, vol. 179(2), pages 481-511, February.
    3. Nick Patterson & Alkes L Price & David Reich, 2006. "Population Structure and Eigenanalysis," PLOS Genetics, Public Library of Science, vol. 2(12), pages 1-20, December.
    4. J. Kruskal, 1964. "Multidimensional scaling by optimizing goodness of fit to a nonmetric hypothesis," Psychometrika, Springer;The Psychometric Society, vol. 29(1), pages 1-27, March.
    5. Aysu Okbay & Jonathan P. Beauchamp & Mark Alan Fontana & James J. Lee & Tune H. Pers & Cornelius A. Rietveld & Patrick Turley & Guo-Bo Chen & Valur Emilsson & S. Fleur W. Meddens & Sven Oskarsson & Jo, 2016. "Genome-wide association study identifies 74 loci associated with educational attainment," Nature, Nature, vol. 533(7604), pages 539-542, May.
    6. Jan Leeuw & Jacqueline Meulman, 1986. "A special Jackknife for Multidimensional Scaling," Journal of Classification, Springer;The Classification Society, vol. 3(1), pages 97-112, March.
    7. Gunnar Andersson & Marit Rønsen & Lisbeth B. Knudsen & Trude Lappegård & Gerda Neyer & Kari Skrede & Kathrin Teschner & Andres Vikat, 2009. "Cohort fertility patterns in the Nordic countries," Demographic Research, Max Planck Institute for Demographic Research, Rostock, Germany, vol. 20(14), pages 313-352.
    8. Bryan N Howie & Peter Donnelly & Jonathan Marchini, 2009. "A Flexible and Accurate Genotype Imputation Method for the Next Generation of Genome-Wide Association Studies," PLOS Genetics, Public Library of Science, vol. 5(6), pages 1-15, June.
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    1. Andras Gezsi & Sandra Auwera & Hannu Mäkinen & Nora Eszlari & Gabor Hullam & Tamas Nagy & Sarah Bonk & Rubèn González-Colom & Xenia Gonda & Linda Garvert & Teemu Paajanen & Zsofia Gal & Kevin Kirchner, 2024. "Unique genetic and risk-factor profiles in clusters of major depressive disorder-related multimorbidity trajectories," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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