Frontal alpha asymmetry across genders as a distinction between major depressive disorder and bipolar disorder

Bipolar disorder (BD) and major depressive disorder (MDD) impose a significant burden worldwide. Misdiagnosis between BD and MDD has long been a challenging issue. Frontal alpha asymmetry (FAA) is one of the most widely studied electroencephalogram (EEG) markers in mental health research. This study utilizes a relatively large sample size to investigate whether FAA can effectively differentiate BD from MDD.

We enrolled 149 participants aged 18-65 years, including 68 with MDD, 51 with BD, and 30 healthy control participants. Resting-state EEG was recorded for 5 min each under eyes-open and eyes-closed conditions. FAA was calculated at FP1/FP2, F3/F4, and F7/F8. Depression and anxiety severity were assessed using HAMD-17 and HAMA.

In males, FAA at F3/F4 was significantly higher in BD than MDD and controls under both conditions (p < 0.05), while no differences were observed at other electrode pairs. In females, no differences appeared in eyes-open recordings. However, in the eyes-closed condition, FAA at FP1/FP2 was lower in BD than MDD (p = 0.004), while FAA at F3/F4 was higher in MDD than controls (p = 0.041). Receiver operating characteristic (ROC) analyses demonstrated good diagnostic performance in males at F3/F4 (AUC = 0.863 and 0.774 for open- and closed-eye, respectively) and moderate accuracy in females at FP1/FP2 under the closed-eye condition (AUC = 0.690).

FAA exhibits distinct patterns in MDD and BD, suggesting its potential as a key biomarker for differentiating the two diseases. Moreover, the study highlights the crucial influence of gender in FAA research.