AUTHOR=Gao Tao , Xiang Han , Wu Qian Nan , Zhu Li Shan , Pei Wan Juan , Fu Wei Jie , Chou Tian Shu TITLE=Advances in the research of comorbid insomnia and depression: mechanisms, impacts, and interventions JOURNAL=Frontiers in Psychiatry VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2025.1468212 DOI=10.3389/fpsyt.2025.1468212 ISSN=1664-0640 ABSTRACT=Insomnia and depression, both significantly impacting public health, are common psychosomatic illnesses that frequently co-occur in the same individual. Not only do these two conditions commonly co-occur, but they also exhibit a bidirectional link, where the existence of one may heighten the risk for the other. Latest research offers compelling evidence of significant overlap in biological, psychological, and sociological aspects in the comorbidity of insomnia and depression. Building on this, we aim to examine the pathophysiology of insomnia and depression, along with their comorbid mechanisms, encompassing biological routes (like genetics, HPA axis, immune-inflammatory activation, neuroendocrine regulation, microbiome alterations, and neural circuits integrating sleep and emotion regulation), as well as psychosocial routes. Consequently, proposing a self-perpetuating and mutually reinforcing “snowball effect” model of comorbid insomnia and depression, and examining corresponding preventative intervention strategies to rectify associated imbalances. Finally, this article encapsulates the challenges in this field of study and the directions for future research. Finally, the paper points out the limitations of current research (cross-sectional data being dominant, and the mechanism of multi-omics dynamics being unknown) and the future direction (longitudinal cohort combined with computational modeling to resolve temporal interactions), which will provide a theoretical basis for precision interventions.