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Updated: Jun 10, 2026

Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
Major depressive disorder with subthreshold bipolarity in the National Comorbidity Survey Replication
Jules Angst1, Lihong Cui, Joel Swendsen
1Department of Psychiatry, Zurich University Psychiatric Hospital, Zurich, Switzerland.
Objective:
There is growing clinical and epidemiologic evidence that major mood disorders form a spectrum from major depressive disorder to pure mania. The authors examined the prevalence and clinical correlates of major depressive disorder with subthreshold bipolarity compared with pure major depressive disorder in the National Comorbidity Survey Replication (NCS-R).
Method:
The NCS-R is a nationally representative face-to-face household survey of the U.S. population conducted between February 2001, and April 2003. Lifetime history of mood disorders, symptoms, and clinical indicators of severity were collected using version 3.0 of the World Health Organization's Composite International Diagnostic Interview.
Results:
Nearly 40% of study participants with a history of major depressive disorder had a history of subthreshold hypo-mania. This subgroup had a younger age at onset, more episodes of depression, and higher rates of comorbidity than those without a history of hypomania and lower levels of clinical severity than those with bipolar II disorder.
Conclusions:
These findings demonstrate heterogeneity in major depressive disorder and support the validity of inclusion of subthreshold mania in the diagnostic classification. The broadening of criteria for bipolar disorder would have important implications for research and clinical practice.
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