Core Insights - The research reveals a common neurobiological mechanism behind the antidepressant effects of ketamine and electroconvulsive therapy (ECT) for treatment-resistant depression, highlighting the role of adenosine signaling [1][2][3] Group 1: Treatment Landscape - Depression affects nearly 100 million people in China, with about one-third of patients being treatment-resistant [1][2] - Ketamine and ECT are currently the two main effective treatments for treatment-resistant depression, but both have significant side effects [2][3] - The study aims to decouple the efficacy of these treatments from their adverse effects by understanding their underlying mechanisms [2][4] Group 2: Research Findings - The research team utilized genetically encoded fluorescent probes to demonstrate that both ketamine and ECT lead to a significant and sustained increase in adenosine levels in key brain regions [2][3] - The study found that the activation of the adenosine pathway by ketamine occurs through the regulation of cellular energy metabolism, rather than the previously believed NMDA receptor pathway [3][4] - Evidence shows that blocking adenosine signaling negates the antidepressant effects of both treatments, while directly activating this pathway produces clear antidepressant effects [2][3] Group 3: Development of New Therapies - The research team has successfully designed a new ketamine derivative that achieves superior antidepressant effects at lower doses with reduced side effects, indicating strong clinical translation potential [4] - A novel non-drug therapy called acute intermittent hypoxia (aIH) has been developed, which effectively activates the brain's adenosine signaling and shows promise as a safe, non-invasive treatment option [5] - The team is collaborating with clinical teams to advance clinical trials for the aIH therapy, aiming to enhance treatment durability and reduce tolerance issues [5]

Core Insights - Chinese scientists have made a significant breakthrough in depression treatment research by revealing the common mechanism behind ketamine and electroconvulsive therapy (ECT), which is the adenosine signaling pathway [1][2][3] - This discovery provides a clear path for developing safer and more effective new treatment options for depression [1][3] Research Collaboration - The research was led by the Beijing Brain Science and Brain-like Research Institute, in collaboration with the Changchun Institute of Applied Chemistry and Peking University [1][2] - The project leader, Luo Minmin, has over 30 years of experience in neuroscience and has made several original contributions in various fields [1][2] Depression Statistics - Depression is one of the most common mental disorders globally, with the World Health Organization estimating over 300 million patients annually [1] - Approximately one-third of patients do not respond well to traditional medications, known as treatment-resistant depression [1] Mechanism of Action - The study utilized advanced gene-encoded fluorescent probe technology to observe that both ketamine and ECT cause a rapid and sustained increase in adenosine levels in key brain areas related to emotional regulation [2][3] - Blocking the brain's reception of adenosine signals negated the antidepressant effects of both therapies, while directly activating this pathway produced clear antidepressant effects [2][3] Drug Development - The research has led to the design and synthesis of more efficient ketamine derivatives that show superior antidepressant effects at lower doses with significantly reduced side effects [2][3] - The study provides a roadmap for developing next-generation drugs that retain the benefits of existing therapies while minimizing adverse effects [2][3] Non-Pharmacological Approaches - The research also opens new avenues for non-drug treatments, such as using acute intermittent hypoxia to activate the adenosine signaling pathway and produce antidepressant effects [3] - This shift from empirical use to mechanism-based precision medicine could revolutionize the treatment of depression [3] Future Directions - The team has applied for patents on related small molecule drugs and hypoxia treatment devices, and has initiated efficacy validation in collaboration with Beijing Anding Hospital [5] - The next steps involve advancing the translation of new drugs and treatment devices to provide groundbreaking solutions for depression treatment [5]