Analysis of diagnosis instability in electronic health records reveals diverse disease trajectories of severe mental illness

Investigations using Electronic Health Records (EHR) databases could enable accurate delineation of psychiatric disease trajectories at an unprecedented scale. Using EHR from a single institution (Clínica San Juan de Dios in Manizales, Colombia), we characterize diagnostic trajectories of >22,000 (ages 4-90, 60% female) individuals treated for severe mental illness (SMI), including schizophrenia (SCZ), bipolar disorder (BD), and severe or recurrent major depressive disorder (MDD). We extracted diagnostic codes, clinical notes, and healthcare use data collected since 2005. Using a subsample of 105 SMI patients, we assessed diagnostic reliability, comparing EHR to clinical chart review. EHR diagnostic codes showed very good agreement with chart review diagnoses (Cohen’s kappa 0.78). Using 3,600 annotated sentences from 2,788 patients, we developed a pipeline for extracting clinical features from the electronic text, which showed high agreement with gold-standard annotations (average F1 0.88). Factors associated with diagnostic instability, defined as changes in diagnosis between successive visits, were identified using mixed-effect logistic regression models. Of SMI patients with >3 visits (n=12,962), 64% had multiple EHR diagnoses; diagnostic switches (19%), comorbidities (30%), and both (15%). While some diagnostic switches are common, such as the switch from MDD to BD (observed in 22% of BD patients), trajectories are highly heterogeneous, with rare trajectories (occurring in <1% of patients) making up the majority (58% of all patients). Predictors of diagnostic instability include time since initial visit (OR 0.56 by visit number, p-value 2e-66), previous diagnostic change (OR= 4.02, p-value 3e-250) and NLP-derived descriptions of delusions (OR 1.50, p-values 2e-18). Our results underline the importance of considering longitudinal rather than cross-sectional diagnoses in psychiatric research and show how high-quality EHR data can contribute to global efforts to understand disease trajectories. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Research reported here was supported by R01MH123157 (to LMOL, CLJ, and NBF), R01MH113078 (to CEB, CLJ, and NBF), R00MH116115 (to LMOL), T32MH073526 (to JFDLH) and the Fulbright Commission in Colombia through a Fulbright-Colciencias grant (to JFDLH). The content is solely the responsibility of the authors and does not necessarily represent the official views of Fulbright or the National Institutes of Health. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All procedures involving human subjects/patients were approved by the Institutional Review Boards at Clinica San Juan de Dios Manizales and University of California, Los Angeles I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes NA