Beyond symptom resolution: Clinical burden and immunometabolic correlates of functional remission after mania

Background Functional outcomes after manic episodes in bipolar disorder (BD) are heterogeneous and likely reflect the interaction between illness burden and biological processes, including systemic inflammation. However, the contribution of immunometabolic factors to functional remission remains unclear.Objective To identify clinical and immunometabolic predictors of functional remission in patients hospitalized for manic episodes.Methods We conducted a retrospective cohort study of 680 manic episodes. Functional outcomes at discharge were assessed using the Global Assessment of Functioning (GAF score ≥ 70). Clinical, demographic, and laboratory data were extracted from routine records. Multivariable logistic regression models were used to identify independent predictors of functional remission.Results Functional remission was achieved in 72.6% of manic episodes. In the final multivariable logistic regression model, remission was independently associated with shorter illness duration, shorter duration of untreated bipolar disorder (DUBD), higher GAF scores at admission, higher platelet-to-lymphocyte ratio (PLR), lower leukocyte levels, female sex, and absence of valproate treatment. However, in mixed-effects analyses accounting for repeated manic episodes, only illness duration, DUBD, GAF score at admission, and PLR remained statistically significant predictors of functional remission. The combined model showed acceptable discriminative ability for predicting functional remission (AUC = 0.780 95% CI 0.740-0.819).Conclusions Functional remission in BD appears to be primarily determined by illness burden, particularly indicators of illness chronicity. Among immunometabolic factors examined, PLR showed the most consistent association with remission outcomes. These findings suggest that immunometabolic markers may contribute to our understanding of the biological mechanisms underlying functional recovery, although their added predictive value beyond clinical variables appears to be limited.