Mixed Features in Recurrent Major Depressive Disorder: Prevalence, Risk Factors, and Clinical Consequences

Mixed features in major depressive disorder (MDD)-the presence of manic symptoms during major depressive episodes (MDEs)-are associated with adverse clinical outcomes. We investigated the prevalence and clinical correlates of mixed features among Korean women with recurrent MDD.

Data (n = 3000) were drawn from the Korean Mood Disorder Genetic Study-Depression, a nationwide case-control study recruiting women aged ≥30 years with recurrent MDD from 47 hospitals across South Korea. Structured clinical interviews assessing depressive symptoms, family history, comorbidities, and psychosocial functioning were administered. Mixed features during MDEs were defined per Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria. Generalized linear models (GLMs) examined associations between mixed features and clinical correlates.

The worst-MDE-based prevalence of mixed features was 4.6%. A family history of manic episodes (odds ratio [OR] = 3.36, 95% confidence interval [CI]: 1.67-6.36) and of MDEs (OR = 1.90, 95% CI: 1.41-2.55) was significantly associated with mixed features. Five worst-MDE symptoms were independently associated with mixed features: increased weight (OR = 2.19, 95% CI: 1.16-4.09), late insomnia (OR = 1.84, 95% CI: 1.07-3.41), slow or mixed thoughts (OR = 1.93, 95% CI: 1.18-3.33), suicidal ideation (OR = 1.96, 95% CI: 1.04-3.94), and diurnal mood variation (OR = 1.94, 95% CI: 1.34-2.81). Mixed features were associated with mood-stabilizer use (lifetime use OR = 2.21, 95% CI: 1.38-3.42; current use OR = 2.53, 95% CI: 1.58-3.92), panic disorder (OR = 2.10, 95% CI: 1.46-2.99), premenstrual syndrome symptoms (rate ratio [RR] = 1.22, 95% CI: 1.08-1.37), and damage by suicide attempts (RR = 1.66, 95% CI: 1.17-2.07).

Although less prevalent in this clinically ascertained sample than in Western samples, mixed features in recurrent MDD exhibit distinct clinical patterns. This finding underscores the importance of screening for mixed features, particularly when associated depressive symptoms are present, to inform early detection and treatment planning.