Irritable Mood and Subthreshold Hypomanic Episodes Correlate with More Severe Major Depression
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Updated: Nov 17, 2025

Author Spotlight: Unveiling the Connection Between Sleep Disorders and Cognitive Symptoms in Depression
Published on: April 26, 2024
Alessandro Serretti1, Diana De Ronchi2, Paolo Olgiati2
1Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy, alessandro.serretti@unibo.it.
Introduction:
Irritable mood (IM) and subthreshold hypomanic symptoms are reported in half and two-fifths of major depressed subjects respectively, but their clinical and prognostic meanings remain unclear. The aim of this study was to test the clinical usefulness of 2 specifiers in DSM-IV major depressive disorder (MDD): IM occurring during an index episode (IM+) and lifetime episodes of elated mood or IM with at least 2 concurrent hypomanic symptoms (subthreshold hypomanic episodes [SHEs]).
Method:
We included 482 outpatients with MDD participating in the Combining Medications to Enhance Depression Outcome study (mean age 43.14 ± 12.46 years, 144 males - 30%). The main aim of the original study was to test whether 2 different medications when given in combination as the first treatment step, compared to 1 medication, would improve antidepressant response.
Results:
IM + subjects (N = 349; 70%) were younger and more often females, with a more severe depression, a more marked social impairment, and more psychiatric comorbidities. The IM + group was also characterized by higher levels of suicidal ideation and more cases of emotional abuse. The combination of IM+ and SHEs was associated with an even more severe clinical picture. Limitations include the post hoc method, incomplete assessment of bipolar validators (e.g., family history of bipolar illness), personality disorders and suicide attempts.
Conclusions:
The presence of IM and SHEs in MDD correlate with an overall more severe clinical condition.
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