• Laura Sakalauskaitė, Luna S Hansen, Julie Margrethe Dubois, Malina Ploug Larsen, Gustavo Miguel Feijóo, Marcus S Carstensen, Kamilla Woznica Miskowiak, Mai Nguyen, Line Katrine Harder Clemmensen, Paul Michael Petersen, and Klaus Martiny.
• New Interventions in Depression Group (NID-Group), Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.
• Ann. Med. 2024 May 11; 56 (1): 23548522354852.

BackgroundMajor depressive disorder (MDD) is a debilitating condition that affects more than 300 million people worldwide. Current treatments are based on a trial-and-error approach, and reliable biomarkers are needed for more informed and personalized treatment solutions. One of the potential biomarkers, gamma-frequency (30-80 Hz) brainwaves, are hypothesized to originate from the excitatory-inhibitory interaction between the pyramidal cells and interneurons. The imbalance between this interaction is described as a crucial pathological mechanism in neuropsychiatric conditions, including MDD, and the modulation of this pathological interaction has been investigated as a potential target. Previous studies attempted to induce gamma activity in the brain using rhythmic light and sound stimuli (GENUS - Gamma Entrainment Using Sensory stimuli) that resulted in neuroprotective effects in Alzheimer's disease (AD) patients and animal models. Here, we investigate the antidepressant, cognitive, and electrophysiological effects of the novel light therapy approach using 40 Hz masked flickering light for patients diagnosed with MDD.Methods And DesignSixty patients with a current diagnosis of a major depressive episode will be enrolled in a randomized, double-blinded, placebo-controlled trial. The active treatment group will receive 40 Hz masked flickering light stimulation while the control group will receive continuous light matched in color temperature and brightness. Patients in both groups will get daily light treatment in their own homes and will attend four follow-up visits to assess the symptoms of depression, including depression severity measured by Hamilton Depression Rating Scale (HAM-D17), cognitive function, quality of life and sleep, and electroencephalographic changes. The primary endpoint is the mean change from baseline to week 6 in depression severity (HAM-D6 subscale) between the groups.

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