Abstract
Background: Bipolar II disorder (BD II) is a chronic and severe mental illness frequently misdiagnosed as major depressive disorder (MDD) due to symptom overlap and the absence of objective diagnostic tools. Consequently, establishing pathophysiological markers to differentiate BD II from MDD is critical. Method: A total of 180 patients were enrolled in the study and allocated to three groups: patients with unipolar depression (UD group; MDD currently experiencing a major depressive episode, n = 60), patients with bipolar II disorder during depressive episodes (BD II group; n = 60), and age- and sex- matched healthy controls (HC; n = 60). Sociodemographic data were collected, and all participants underwent psychological assessments using the 7-item Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and 32-item Hypomania Checklist (HCL-32). Additionally, all participants passed auditory brain stem response (ABR) test and subsequently underwent event-related potential (ERP) examinations. Results: No significant differences were observed in demographic characteristics between the three groups, including age, sex, educational level, marital status, and socioeconomic status (all P > 0.05). Compared with HC, patients in both the UD and BD II groups showed significantly longer reaction time (HC: 254.4 ± 43.8 ms; UD: 297.7 ± 72.2 ms; BD II: 300.3 ± 70.0 ms; P = 0.028) and larger amplitude of P2-N2 complex (HC: 5.7 ± 4.4 μV; UD: 8.1 ± 4.8 μV; BD II: 8.6 ± 5.6 μV; P = 0.001) in P300 paradigm. The BD II group exhibited longer S2-P50 latency than the UD group (UD: 50.4 ± 11.1 ms vs. BD II: 63.2 ± 11.5 ms; P = 0.025). Additionally, the BD II group had prolonged N2 latency compared to HC (BD II: 216.2 ± 22.1 ms vs. HC: 205.2 ± 16.5 ms; P = 0.044). Conclusions: This study may identify neurophysiological distinctions between BD II and UD depression, notably a prolonged S2-P50 latency in BD II.