Core Insights - The research published in the journal "Nature" confirms that the adenosine signaling pathway is a common core mechanism for the rapid antidepressant effects of ketamine and electroconvulsive therapy (ECT), providing a clear target for developing safer and more effective depression treatments [1][2] Group 1: Research Findings - Approximately one-third of treatment-resistant depression patients do not respond well to traditional medications, highlighting the need for effective interventions like ketamine and ECT, which have known efficacy but also significant side effects [1] - The research team utilized genetically encoded adenosine probes and fiber photometry to monitor adenosine levels in the brains of mice, discovering that both ketamine and ECT rapidly and persistently elevated adenosine levels in key brain regions associated with emotional regulation [1][2] - The study identified that the adenosine A1 and A2A receptors are essential for the antidepressant effects, as their knockout or blockade resulted in the complete loss of the antidepressant effects of both therapies [1] Group 2: Mechanism Exploration - Ketamine was found to directly inhibit the mitochondrial tricarboxylic acid cycle, regulating cellular energy metabolism and increasing intracellular adenosine reserves, which are released extracellularly, independent of the traditional NMDA receptor inhibition mechanism [2] - A ketamine derivative, deketamine, was developed, showing stronger antidepressant efficacy and weaker side effects related to motor hyperactivity [2] - The proposed "intermittent hypoxia intervention" can safely induce adenosine release in the brain, achieving rapid antidepressant effects in depression model mice [2] Group 3: Collaborative Efforts and Future Directions - The research was led by the laboratory of Luo Minmin, in collaboration with the Changchun Institute of Applied Chemistry and Peking University, addressing a long-standing mystery in the field of antidepressant mechanisms [2] - This study paves the way for transitioning rapid antidepressant therapies from empirical use to precision medicine, laying a solid foundation for the development of small molecule new drugs and non-drug intervention techniques [2] - Clinical trials for related non-drug therapies have already commenced, with expected phased results by 2026 [2]