Role of neural oscillations in depression: highlights on gamma oscillations

Depression is a prevalent and debilitating psychiatric disorder traditionally conceptualized as monoaminergic dysregulation. Although this view has guided pharmacotherapeutic development for decades, its clinical and mechanistic limitations have spurred research into alternative frameworks, particularly those focusing on network-level dysfunctions. Within this evolving framework, neural oscillations, especially in the frequency of gamma oscillations (30-80 Hz), serve as a critical windowt into the dynamics of the large-scale brain network. Therefore, this review summarizes a substantial body of evidence positing a central role for aberrant gamma oscillations in the pathophysiology of depression. We first synthesize the neurobiological basis of gamma oscillations and critique their crucial relationship with synaptic plasticity, proposing that gamma impairments may underpin key cognitive and affective deficits observed in this disorder. Notably, we critically examine the complex effects of conventional antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), and neuromodulation therapies like repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation (DBS) on gamma oscillations. Finally, we discuss emerging gamma oscillation-targeting therapies like 40 Hz flickering light therapy and future directions. In summary, we conclude that gamma oscillations represent not an epiphenomenon but a fundamental pathophysiological hub and a promising therapeutic target, paving the way for more precise and effective treatments for depression.