Core Insights - A Chinese research team has identified a common mechanism driving the rapid antidepressant effects of ketamine and electroconvulsive therapy (ECT), focusing on the adenosine signaling pathway in the medial prefrontal cortex [2][5][12]. Group 1: Research Findings - The study published in the journal Nature confirms that both ketamine and ECT induce a significant and sustained increase in adenosine levels in the brain, which is crucial for their antidepressant effects [2][5]. - The research utilized gene-encoded fluorescent probes to observe adenosine signaling in live animal brains, marking a significant advancement in understanding the biological mechanisms behind these therapies [5][12]. - The team conducted experiments that demonstrated blocking adenosine signaling negated the antidepressant effects of both treatments, while activating this pathway produced similar effects in animal models [5][12]. Group 2: Development of New Treatments - The research has led to the design of new candidate drugs with fewer side effects, as well as a non-drug therapy called intermittent hypoxia (aIH), which is currently in clinical validation [2][12][15]. - The new drug candidates, including "dechloroketamine" (DCK), have shown promising results in animal tests, achieving significant adenosine release at lower doses compared to traditional ketamine [12][13]. - The aIH therapy aims to safely induce adenosine production through controlled low-oxygen breathing, with the potential for home use if clinical trials prove effective [14][15]. Group 3: Historical Context and Challenges - The research journey spanned over twelve years, with initial challenges in linking the immediate effects of ketamine on neural activity to its delayed antidepressant outcomes [6][7]. - A pivotal moment occurred in 2019 when the team successfully observed adenosine signaling dynamics in response to ketamine, leading to a renewed focus on this pathway [8][11]. - The team faced setbacks with traditional drug development approaches, prompting a shift towards exploring the anti-inflammatory properties of ketamine as a potential breakthrough [6][7].

Core Insights - A Chinese research team has identified a common biological mechanism driving the rapid antidepressant effects of ketamine and electroconvulsive therapy (ECT), focusing on the adenosine signaling pathway in the medial prefrontal cortex [3][6][12] - This discovery opens new avenues for antidepressant treatments, leading to the development of candidate drugs with fewer side effects and a non-drug therapy called intermittent hypoxia, which is currently in clinical validation [3][13][19] Group 1: Research Findings - The study published in the journal Nature confirms that both ketamine and ECT induce a significant and sustained increase in adenosine levels in the brain, which is crucial for their antidepressant effects [3][6][12] - The research utilized gene-encoded fluorescent probes to observe adenosine signaling in live animal brains, marking a significant advancement in understanding the mechanisms behind these therapies [6][10] Group 2: Development of New Therapies - The research team is designing new drug candidates that effectively activate the adenosine pathway while minimizing side effects, with over 30 new derivatives of ketamine already synthesized and tested [13][14] - The promising candidate, "dechloroketamine" (DCK), showed comparable adenosine release effects at lower doses than traditional ketamine, indicating a potential for reduced side effects [14] Group 3: Non-Drug Therapy Approach - The team is also developing a non-drug therapy, intermittent hypoxia, which aims to safely induce adenosine production through controlled low-oxygen breathing [15][18] - Clinical trials for this therapy are set to begin, with expectations that it could provide a low-cost, non-invasive treatment option for patients with treatment-resistant depression [19]