Advancements in drug intervention research for stress-related psychiatric disorders

<p indent="0mm">Stress-related mental disorders, including anxiety disorders, depression, and post-traumatic stress disorder (PTSD), have become a serious threat to public mental health in China. The pathogenesis of these disorders is complex and exhibits significant individual variability, which limits the efficacy of traditional antidepressant and anxiolytic medications. To overcome these treatment challenges, exploring novel drug targets has become a critical focus. With the progress of brain science technologies, the core neural circuits, cells, and molecular mechanisms associated with stress-related mental disorders have been gradually revealed, providing new directions for drug target discovery. Specifically, (i) developing treatment plans for specific neural circuit mechanisms of stress-related mental disorders, early intervention in critical time Windows, and behavioral reshaping of neural circuits may be feasible paths to achieve accurate and effective treatment. (ii) Multi-omics technologies have revealed the spatiotemporal heterogeneity of diseases, providing multidimensional data support for mechanistic analysis. By integrating cross-species disease models and clinical data, combined with artificial intelligence technologies, dynamic disease network maps can be constructed to identify key regulatory nodes and develop multi-target intervention strategies. (iii) Research into mechanisms of stress vulnerability, resilience, and gender differences provides new perspectives for drug development. (iv) Psychoactive drugs (e.g., ketamine, psilocybin) and traditional medicine (e.g., herbal compounds) exhibit multi-target mechanisms, which can comprehensively regulate neurotransmitters, modulate synaptic plasticity, and control immune and oxidative stress levels. Combined with modern omics technologies, these approaches may reveal dynamic action networks, providing scientific evidence for the pathogenesis of stress-related psychiatric disorders and the discovery of new drug targets. (v) The integration of predictive biomarkers of efficacy with psychiatric drug development will provide important evidence for personalized treatment plans. However, current challenges such as insufficient test reliability, weak interpretability, and high risk of overfitting must be addressed through the use of artificial intelligence technologies to improve the success rate of drug development. This review, based on the 375th “Shuangqing Forum”, synthesizes recent progress in pharmacological research on stress-related mental disorders, outlines future directions, and proposes funding priorities to propel China’s drug development efforts toward more effective and precise therapeutic paradigms.