Monahan, Patrick O.Stump, TimothyCoryell, William H.Harezlak, JaroslawMarcoulides, George A.Liu, HaiSteeger, Christine M.Mitchell, Philip B.Wilcox, Holly C.Hulvershorn, Leslie A.Glowinski, Anne L.Iyer-Eimerbrink, Priya AnapurnaMcInnis, MelvinNurnberger, John I. Jr.2015-10-082015-10-082015-07Monahan, P. O., Stump, T., Coryell, W. H., Harezlak, J., Marcoulides, G. A., Liu, H., ... & Nurnberger, J. I. (2015). Confirmatory test of two factors and four subtypes of bipolar disorder based on lifetime psychiatric co-morbidity. Psychological medicine, 45(10), 2181-2196.https://hdl.handle.net/1805/7222Background The first aim was to use confirmatory factor analysis (CFA) to test a hypothesis that two factors (internalizing and externalizing) account for lifetime co-morbid DSM-IV diagnoses among adults with bipolar I (BPI) disorder. The second aim was to use confirmatory latent class analysis (CLCA) to test the hypothesis that four clinical subtypes are detectible: pure BPI; BPI plus internalizing disorders only; BPI plus externalizing disorders only; and BPI plus internalizing and externalizing disorders. Method A cohort of 699 multiplex BPI families was studied, ascertained and assessed (1998–2003) by the National Institute of Mental Health Genetics Initiative Bipolar Consortium: 1156 with BPI disorder (504 adult probands; 594 first-degree relatives; and 58 more distant relatives) and 563 first-degree relatives without BPI. Best-estimate consensus DSM-IV diagnoses were based on structured interviews, family history and medical records. MPLUS software was used for CFA and CLCA. Results The two-factor CFA model fit the data very well, and could not be improved by adding or removing paths. The four-class CLCA model fit better than exploratory LCA models or post-hoc-modified CLCA models. The two factors and four classes were associated with distinctive clinical course and severity variables, adjusted for proband gender. Co-morbidity, especially more than one internalizing and/or externalizing disorder, was associated with a more severe and complicated course of illness. The four classes demonstrated significant familial aggregation, adjusted for gender and age of relatives. Conclusions The BPI two-factor and four-cluster hypotheses demonstrated substantial confirmatory support. These models may be useful for subtyping BPI disorders, predicting course of illness and refining the phenotype in genetic studies.en-USPublisher Policybipolar disorderco-morbidityconfirmatory factor analysisArticle