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.
Highlights
Schizophrenia is a heterogeneous disorder, exhibiting variability in presentation and outcomes that complicate treatment and recovery
The prevalence of other psychiatric diagnoses in individuals diagnosed with schizophrenia was more than 5-fold higher at age of censoring than among the population controls (relative risk (RR) ranging from 6.2 (95% confidence interval (CI): 5.0–7.6) for eating disorders to 18.7 (CI: 16.4–21.3) for substance abuse; Table 1)
A substantial proportion of childhood disorders, defined by a typically early onset in population cohorts, were diagnosed after the first diagnosis of schizophrenia, such that they occurred in adolescence or adulthood
Summary
Schizophrenia is a heterogeneous disorder, exhibiting variability in presentation and outcomes that complicate treatment and recovery. The Psychiatric Central Research Register (PCRR)[23] follows the population from birth in a longitudinal and prospective manner, providing a unique, time-stamped, and reliable[23,25,26,27,28] diagnoses for an individual at each hospital contact. These data, more closely reflect real-world clinical practice than retrospective casecontrol diagnoses because they objectively catalog preceding and succeeding psychiatric contacts. A systematic, data-driven study of life-course patterns of comorbid diagnoses and their relation to etiological factors has not been pursued but could contribute greatly to how we understand heterogeneity within schizophrenia
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