Stability of depressive and manic symptoms as a predictor of conversion from major depressive disorder to bipolar disorder: A prospective cohort study
Han Qi, Zizhao Feng, Yuan Feng, Le Xiao, Ruinan Li, Xiaoya Li, Jing Liu, Xueshan Zhang, Jingjing Zhou, Gang WangAbstract
Background
Bipolar disorder (BD) is characterized by mood fluctuations and is prone to misdiagnosis as major depressive disorder (MDD). Quantifying the relationship between symptom fluctuations and conversion risk is essential for early identification.
Methods
In a national prospective cohort of patients with MDD (enrolled from May 2022 to February 2025), depressive and manic symptoms were assessed using clinician-rated and self-report instruments. Two measures were calculated: the time in target range (TTR), the proportion of numbers of evaluations with scores below predefined clinical cutoffs; and Statistical Process Control (SPC) stability, evaluated with a person-specific approach defining each individual’s normal fluctuation range via their 25th–75th percentiles. The outcome was the incidence of manic or hypomanic episodes that met the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria. Cox regression models were used to evaluate the associations of the TTR and SPC with the conversion to BD.
Results
Among the 2,367 eligible patients with MDD (mean [SD] age, 29.88 [9.79] years; 792 [33.46%] male), 69 (2.92%) converted to BD in the 52-week follow-up. During weeks 0-8, higher TTR of the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16) (cutoff set at ≤10) and the 33-item Hypomania Checklist (HCL-33) (cutoffs set at ≤7 and ≤15) were significantly associated with a lower risk of conversion between Weeks 8 and 52. Additionally, a greater SPC-evaluated stability of the HCL-33 scores was significantly associated with lower conversion risk over the same period.
Conclusions
While further validation in independent samples is still needed, continuous monitoring of hypomanic symptoms, especially evaluated with the HCL-33, may be of clinical significance for the early identification of conversion to BD.