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It is unknown whether MDD is a comorbidity of BD or its earlier stage, and no consensus exists on individual conversion predictors, delaying BD\u2019s timely recognition and treatment. We aimed to build a predictive model of MDD to BD conversion and to validate it across a multi-national network of patient databases using the standardization afforded by the Observational Medical Outcomes Partnership (OMOP) common data model. Five \u201ctraining\u201d US databases were retrospectively analyzed: IBM MarketScan CCAE, MDCR, MDCD, Optum EHR, and Optum Claims. Cyclops regularized logistic regression models were developed on one-year MDD-BD conversion with all standard covariates from the HADES PatientLevelPrediction package. Time-to-conversion Kaplan-Meier analysis was performed up to a decade after MDD, stratified by model-estimated risk. External validation of the final prediction model was performed across 9 patient record databases within the Observational Health Data Sciences and Informatics (OHDSI) network internationally. The model\u2019s area under the curve (AUC) varied 0.633\u20130.745 (<jats:italic>\u00b5<\/jats:italic> = 0.689) across the five US training databases. Nine variables predicted one-year MDD-BD transition. Factors that increased risk were: younger age, severe depression, psychosis, anxiety, substance misuse, self-harm thoughts\/actions, and prior mental disorder. AUCs of the validation datasets ranged 0.570\u20130.785 (<jats:italic>\u00b5<\/jats:italic> = 0.664). An assessment algorithm was built for MDD to BD conversion that allows distinguishing as much as 100-fold risk differences among patients and validates well across multiple international data sources.<\/jats:p>","DOI":"10.1038\/s41398-021-01760-6","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T11:13:41Z","timestamp":1639998821000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Predictors of diagnostic transition from major depressive disorder to bipolar disorder: a retrospective observational network study"],"prefix":"10.1038","volume":"11","author":[{"given":"Anastasiya","family":"Nestsiarovich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna M.","family":"Reps","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3217-4147","authenticated-orcid":false,"given":"Michael E.","family":"Matheny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott L.","family":"DuVall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine E.","family":"Lynch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura","family":"Beaton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinzhuo","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2869-0237","authenticated-orcid":false,"given":"Matthew","family":"Spotnitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R.","family":"Pfohl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9385-7158","authenticated-orcid":false,"given":"Nigam H.","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen Olga","family":"Torre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian G.","family":"Reich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3678-9862","authenticated-orcid":false,"given":"Dong Yun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7434-7996","authenticated-orcid":false,"given":"Sang Joon","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5052-6399","authenticated-orcid":false,"given":"Seng Chan","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4989-3287","authenticated-orcid":false,"given":"Rae Woong","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick B.","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1994-2893","authenticated-orcid":false,"given":"Christophe G.","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"key":"1760_CR1","unstructured":"GBD. 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