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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.
Schizophrenia is a complex disorder where individuals experience different symptoms and outcomes that can be captured by patterns in other diagnoses. Here the authors use computational approaches to summarize these patterns and suggest they are associated with genetic and environmental exposure.
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1 Mental Health Services Capital Region of Denmark, Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Copenhagen, Denmark (GRID:grid.466916.a) (ISNI:0000 0004 0631 4836); iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300)
2 Copenhagen University Hospital, Copenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen, Copenhagen, Denmark (GRID:grid.4973.9) (ISNI:0000 0004 0646 7373); University of Copenhagen, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X)
3 iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Aarhus University Hospital, Risskov, Denmark (GRID:grid.154185.c) (ISNI:0000 0004 0512 597X)
4 iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Aarhus University, Department of Biomedicine and iSEQ-Centre for Integrative Sequencing, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); Aarhus University, Center for Genomics and Personalized Medicine, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722)
5 iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Statens Serum Institut, Department for Congenital Disorders, Copenhagen, Denmark (GRID:grid.6203.7) (ISNI:0000 0004 0417 4147)
6 iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Aarhus University, Center for Genomics and Personalized Medicine, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); Aarhus University, Business and Social Sciences, National Centre for Register-Based Research, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722)
7 iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Copenhagen University Hospital, Copenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen, Copenhagen, Denmark (GRID:grid.4973.9) (ISNI:0000 0004 0646 7373)
8 University of California, Los Angeles, Department of Neurology, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718); University of California, Los Angeles, Department of Human Genetics, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718); University of California, Los Angeles, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718)
9 Mental Health Services Capital Region of Denmark, Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Copenhagen, Denmark (GRID:grid.466916.a) (ISNI:0000 0004 0631 4836); iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); University of California, Center for Human Development, San Diego, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242)
10 University of California, Los Angeles, Department of Neurology, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718); University of California, Los Angeles, Department of Human Genetics, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718); University of California, Los Angeles, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718); University of California Los Angeles, Program in Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718)
11 Mental Health Services Capital Region of Denmark, Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Copenhagen, Denmark (GRID:grid.466916.a) (ISNI:0000 0004 0631 4836); iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); The Translational Genomics Research Institute (TGEN), Neurogenomics Division, Phoenix, USA (GRID:grid.250942.8) (ISNI:0000 0004 0507 3225)
12 Mental Health Services Capital Region of Denmark, Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Copenhagen, Denmark (GRID:grid.466916.a) (ISNI:0000 0004 0631 4836); iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); University of Copenhagen, Center for GeoGenetics, Globe Institute, Faculty of Health and Medical Sciences, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X); University of Copenhagen, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X)
13 Mental Health Services Capital Region of Denmark, Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Copenhagen, Denmark (GRID:grid.466916.a) (ISNI:0000 0004 0631 4836); iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); University of California, Division of Biostatistics and Department of Radiology, Population Neuroscience and Genetics Lab, San Diego, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242)