中国团队破解抗抑郁“谜题”，北京脑所罗敏敏：十二年求索催生新疗法 低氧设备有望成为家用治疗仪

Core Insights - The World Health Organization reports approximately 332 million people suffer from depression globally, with about one-third experiencing treatment-resistant depression. In China, around 95 million people are affected by depression. Current treatments face challenges such as significant side effects and a lack of understanding of underlying mechanisms [1][2]. Research Breakthrough - A research team from Beijing Brain Science and Brain-Inspired Research Institute has identified a common mechanism driving the rapid antidepressant effects of both ketamine and electroconvulsive therapy (ECT), specifically through the adenosine signaling pathway in the medial prefrontal cortex (mPFC) [1][3][4]. - This discovery provides a new biological target for depression treatment and has led to the development of candidate drugs with fewer side effects and a non-drug therapy called intermittent hypoxia (aIH), which is currently in clinical validation [1][3][7]. Research Journey - The research journey spanned twelve years, with significant progress made after an unexpected finding in 2019. The team utilized gene-encoded fluorescent probes to observe adenosine signaling in live animal brains, confirming that both ketamine and ECT lead to a rapid increase in adenosine levels in the mPFC [2][3][5][6]. - Initial challenges included inconsistent results in early experiments and the failure of traditional drug development approaches based on ketamine's known targets [4][5]. Drug Development - The team has designed over 30 new ketamine derivatives, with "dechloroketamine" (DCK) showing promising results in inducing adenosine release at lower doses compared to traditional ketamine, while also exhibiting fewer side effects [7][8]. - The development of these new molecules is expected to take 3 to 5 years to complete all necessary clinical trials before market introduction [8]. Non-Drug Therapy - The team is also exploring a non-drug therapy, intermittent hypoxia, which aims to induce adenosine production through controlled low-oxygen breathing. This method has entered clinical trials with the potential for home use [9][10][11]. - If proven effective, this therapy could provide a non-invasive, convenient, and low-cost treatment option for depression patients [11].