Parietal alpha asymmetry as a diagnostic marker for depression and a predictive biomarker for anhedonia improvement after melatonergic antidepressant treatment

Background Major depressive disorder (MDD) is often marked by anhedonia, a symptom poorly addressed by first-line antidepressants. While frontal alpha asymmetry (FAA) has been widely studied, findings are inconsistent. Recent evidence suggests parietal alpha asymmetry (PAA) may better capture reward-related dysfunction. Methods We examined resting-state EEG alpha asymmetry in 84 unmedicated MDD patients and 143 healthy controls (HCs). Patients received 8 weeks of agomelatine, a melatonergic antidepressant. Anhedonia was assessed with the Snaith-Hamilton Pleasure Scale (SHAPS) and the 5-item anhedonia subscale of the Montgomery–Åsberg Depression Rating Scale (MADRS). Results At baseline, MDD patients showed reduced PAA, especially at P7-P8, distinguishing them from HCs (AUC = 0.85). After treatment, depressive symptoms, anxiety, cognition, and anhedonia improved significantly. Lower baseline P3-P4 asymmetry predicted greater improvement in clinician-rated anhedonia, whereas FAA showed no predictive value. Sex-stratified analyses indicated F3-F4 abnormalities were specific to females, while P7-P8 changes were robust across sexes. Conclusions PAA, particularly at P7-P8, demonstrated diagnostic utility, while P3-P4 asymmetry was associated with treatment-related improvement in anhedonia. This study extends prior work by including a larger unmedicated MDD cohort, focusing on melatonergic treatment, and employing subitem-level anhedonia measures. Findings support PAA as a state-sensitive biomarker for diagnostic classification and prognosis in MDD, warranting replication and mechanistic investigation.