Altered gamma oscillations and beta-gamma coupling in drug-naive first-episode major depressive disorder: Association with sleep and cognitive disturbance

Objective: Gamma oscillations contribute to the pathogenesis mechanisms of major depressive disorder (MDD) have been proposed, but gamma activity is not well characterized. This study is the first attempt to investigate the altered gamma oscillations in first-episode MDD, particularly the beta-gamma coupling, and to determine the potential symptomatic relationship with the identified gamma dysregulation. Methods: Resting electroencephalography was recorded for 43 drug-naive first-episode MDD and 57 healthy control (HC) subjects. Integrated analysis of relative spectral power, weighted phase lag index, and phase --amplitude coupling (PAC) were utilized to reveal the alterations of gamma activities. Pearson's correlation was implemented to identify the relationship between altered gamma activities and the clinical depressive symptoms, which were categorized into four factors: anxiety somatization, retardation, cognitive disturbance, and sleep disturbance. Results: Compared with HC subjects, MDD patients showed not only significantly decreased gamma powers in the left temporal and the bilateral occipital regions but also weakened gamma connectivity between the left hemisphere and the right frontal region. Furthermore, attenuated beta-gamma PAC of MDD patients was observed in the left temporal regions. Importantly, the suppression of left occipital mid-and high gamma os-cillations were negatively correlated with sleep disturbance, while the deficits in left temporal beta-mid-gamma PAC and beta-high gamma PAC showed negative correlations with cognitive disturbance.Limitations: Important limitations are the small sample size and the possible inclusion of bipolar depression in the MDD group. Conclusions: Our findings provide the first evidence that in first-episode MDD, aberrant gamma powers and beta-gamma coupling are associated with sleep and cognitive impairments, respectively, deepening our un-derstanding of the physiological mechanisms underlying sleep and cognitive symptoms in first-episode MDD. Altered gamma oscillations emerge as promising biomarkers for diagnosing MDD.