The Mixed Tendency in Bipolar Disorder: An Operational Proposal for the Integration of Mixed Episodes in Predominant Polarity

J Clin Med. 2023 Nov 29;12(23):7398. doi: 10.3390/jcm12237398.

Abstract

Predominant Polarity (PP) is an established specifier of Bipolar Disorder (BD), holding significant clinical implications. Nevertheless, there exists no consensus on how to incorporate mixed states into PP, leaving patients prone to mixed recurrences that are unclassified. In a comprehensive study involving 701 euthymic BD patients, we sought to redefine PP by introducing a novel metric, the "mixed tendency", and establish a practical threshold to identify patients with a "mixed phenotype". Furthermore, we investigated potential associations between the mixed phenotype and specific PP categories. Our findings revealed that the mixed tendency correlated significantly with early BD type I, lifetime suicide attempts, self-aggressive behaviour, and lifetime number of affective episodes (>5). Using a ROC curve analysis, we determined an optimal cut-off point for the mixed tendency at 0.228, suggesting that patients with ~25% of lifetime mixed episodes relative to total affective episodes should be identified as having a mixed phenotype. Notably, the mixed phenotype was positively associated with undetermined PP and negatively with manic and depressive PP. This study introduces a promising approach to incorporating mixed episodes into the PP definition, potentially enabling tailored interventions for patients with a substantial history of mixed episodes. However, further research in large, longitudinal cohorts is essential to validate these findings.

Keywords: bipolar disorder; course specifier; mixed episodes; mixed tendency; predominant polarity; rapid cycling; suicide.

Grants and funding

The project that gave rise to these results received the support of a fellowship from the “La Caixa” Foundation (ID 100010434). A.M. has received a grant (PI19/00672) from the Instituto de Salud Carlos III Subdirección General de Evaluación y Fomento de la investigación, Plan Nacional 2019–2022.