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Updated: Jun 12, 2026

Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
Morbidity in 303 first-episode bipolar I disorder patients
Ross J Baldessarini1, Paola Salvatore, Hari-Mandir Kaur Khalsa
1Department of Psychiatry, Harvard Medical School, Boston, MA, USA. rjb@mclean.org
Objectives:
To test the hypotheses that: (i) depressive-dysthymic-dysphoric (D-type) morbidity is more prevalent than manic-hypomanic-psychotic (M-type) morbidity even from first episodes of bipolar I disorder (BPD-I) and despite treatment; (ii) initial presentations predict later morbidity; (iii) morbidity varies internationally; and (iv) early and later morbidity are similar.
Methods:
We followed SCID-based, DSM-IV BPD-I patients (n = 303) systematically and prospectively for two years to estimate the percent of weeks in specific morbid states from first lifetime major episodes.
Results:
Total morbidity accounted for 44% of the first two years, and D-type exceeded M-type illnesses by 2.1-fold (30%/14%) among morbidities ranking: mixed states (major + minor) >or= dysthymia >or= mania >or= major depression > hypomania > psychosis. In 164 cases, morbidities at 0.5-2.5 and 2.5-4.5 years were very similar. Depressive or mixed initial episodes predicted a 3.6-fold excess of D-type morbidity, and initial M-type episodes predicted a 7.1-fold excess of M-type morbidity over two years. Morbidity in European (EU) sites was nearly half that in the U.S., and 22% greater overall among men than women. In five comparable studies, illness accounted for 54% of follow-up time, and the ratio of D/M morbidity averaged 3.0.
Conclusions:
In accord with four midcourse studies, morbidity from BPD-I onset, despite treatment by community standards, averaged 44%, was 68% D-type morbidity, and was strongly predicted by first-episode polarity. Lower morbidity in EU than U.S. sites may reflect differences in healthcare or social systems.
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