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

BACKGROUND

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.

METHODS

Fifty adults with BD were recruited for the BADAS Study and completed the Bipolar Disorder Symptom Scale (BDSx) 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.

RESULTS

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).

CONCLUSIONS

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.