Temporal dynamics of mixed symptom configurations in bipolar disorder: An intensive longitudinal study

Mixed symptom presentations in bipolar disorder (BD) are clinically consequential, but their short-term temporal organization remains poorly understood. Using ecological momentary assessment (EMA), we mapped transitions across depressive, hypo/manic, co-symptomatic, and mixed symptom configurations and examined the symptom context surrounding mixedness.

Fifty adults with BD were recruited for the BADAS Study and completed the Bipolar Disorder Symptom Scale (BDS_x) twice daily over 123 days on average (3 to 14 months). Symptom presentations were classified into 10 mutually exclusive configurations spanning asymptomatic, depressive, hypo/manic, co-symptomatic, and mixed symptom configurations. We characterized 9627 consecutive within-person transitions, modeled predictors of entry into mixedness, and examined prospective associations between the underlying continuous symptom dimensions.

Overall, 42.3% of transitions remained in the same symptom configuration. Mixedness showed increasing short-term continuity with severity: 60.1%, 68.4%, and 75.0% of assessments remained mixed following low, moderate, and clinical-range mixedness, respectively. Depression-containing configurations accounted for 88.6% of 925 entries into mixedness and 88.6% of 932 exits. Among 493 complete nonmixed-mixed-nonmixed sequences, 77.7% were depression-containing on both sides. In prospective analyses restricted to transitions within 12 h, within-person elevations in depression predicted subsequent hypo/ mania after accounting for prior hypo/mania and elapsed time (standardized β = 0.077, 95% CI [0.048, 0.106], p < .001). The reciprocal association was smaller (β = 0.026, 95% CI [-0.003, 0.055], p = .077), and the two pathways differed significantly (p = .019).

Mixed symptom configurations showed structured short-term persistence and occurred predominantly within depression-containing symptom contexts. Prospective dimensional analyses additionally identified modest temporal asymmetry between depressive and hypo/manic symptoms independent of the categorical definition of mixedness.