A bibliometric and micro‑interpretation review that maps research on the comorbidity of depression and type 2 diabetes, emphasizing HPA axis and BDNF mechanisms and noting links to Parkinson's disease and obesity.

While primarily a high‑level review with limited direct translational data, it flags BDNF and stress‑axis pathways that overlap with PD‑relevant neuroprotection and metabolic/inflammatory mechanisms, pointing to potential biomarker and repurposing hypotheses for Parkinson's therapeutic research.

AIMS: This study aimed to address the lack of comprehensive reviews on the comorbidity between depression and type 2 diabetes mellitus (T2DM) by investigating their complex connections and identifying emerging research trends. METHODS: We conducted an in-depth review combining macro bibliometric analysis and micro content interpretation of literature. Based on the bibliometric analysis of 3,986 papers in Web of Science Core Collection and 238 clinical trials in PubMed published between 2016 and 2025, the institutions, countries, authors and keywords were investigated, and the research maps were drawn by bibliometric software such as VOSviewer, Citespace and Bibliometrix. Meanwhile, micro interpretation entails in-depth content analysis of key articles to develop personal insights. RESULTS: The analysis identified 3,986 relevant papers and 238 clinical trials, revealing a consistent overall growth in research volume. Key contributing entities and potential future research hotspots are mapped, such as the link between comorbidity and Parkinson's disease and obesity. Also, our micro-interpretation identified the comorbidity mechanism through hypothalamic pituitary adrenal axis (HPA axis) and Brain derived neurotrophic factor (BDNF) and integrated treatment strategy of depression and T2DM. CONCLUSION: The results of the study outlined the evolving knowledge and research focus in this field. This study provides a comprehensive review of the comorbidity of depression and T2DM, emphasizing the mechanism and treatment of the comorbidity. The current research focus is on the HPA axis and BDNF, and the integrated treatment idea to solve depression and T2DM at the same time has the potential to change in chronic disease management and clinical practice.