Clinical and metabolic correlates of DSM-5 mixed features in subjects with bipolar depression and mania: A cross-sectional study

Objective: Evidence on the clinical and metabolic characterization of mixed features (MFs) in bipolar disorder (BD) is limited. We performed a cross-sectional study analyzing clinical and metabolic correlates of MFs in people with bipolar depression or mania/hypomania.Methods: We included people with BD consecutively admitted for inpatient treatment from May 2020 to July 2023 as part of the Northern Milan Area Cohort (NOMIAC) project. The SCID-5 was used to confirm the diagnosis and assess DSM-5 specifiers. Young Mania Rating Scale and Montgomery-Asberg Depression Rating Scale were used to measure symptom severity. Information on socio-demographic, clinical, and metabolic conditions - including obesity, diabetes, hypertension, dyslipidemia, and hypothyroidism - were collected. Multiple logistic regression models were used to compare clinical and metabolic correlates between subjects with and without DSM-5 MFs.Results: We included 163 inpatients with BD (111 admitted for a manic/hypomanic episode and 52 for a major depressive episode), 39 of whom with MFs. The overall logistic regression model showed that MFs were associated with anxious distress (z = 2.44; p = 0.015) and obesity (z = 2.39; p = 0.017), also being less frequent among moderately/markedly ill people as compared with those borderline/mildly ill (z = 2.71; p = 0.007). Additional analyses corroborated the association between MFs and these characteristics in people with a depressive episode, though not in those with mania/hypomania.Conclusion: Notwithstanding some limitations, our study provides additional insight into the characterization of individuals with MFs, highlighting that anxious distress and symptom severity, along with obesity, may represent core features helpful for the assessment and management of MFs in BD.