BDNF mediates the heart-brain axis: implications for cardiovascular diseases and mental disorders

Eur Arch Psychiatry Clin Neurosci. 2025 Apr 29. doi: 10.1007/s00406-025-02016-w. Online ahead of print.

ABSTRACT

The comorbidity of cardiovascular diseases (CVDs) and mental disorders (MD) has become a significant challenge in modern medicine, severely affecting patients’ quality of life and prognosis. The heart-brain axis, a bidirectional pathway connecting the central nervous system and the cardiovascular system, plays a critical role in the comorbidity mechanisms of CVDs and MD. In recent years, brain-derived neurotrophic factor (BDNF) has emerged as a key molecule in the study of CVDs and MD. By binding with high affinity to TrkB receptors and activating various signaling pathways, BDNF exerts multiple functions in both the nervous and cardiovascular systems. BDNF may participate in the pathogenesis of CVDs combined with MD through multiple mechanisms such as regulating inflammatory responses, oxidative stress (OS), and the hypothalamic-pituitary-adrenal (HPA) axis, making it a promising new target for future diagnosis and treatment. This review systematically summarizes the mechanisms by which BDNF functions in heart-brain comorbidity, particularly its multifaceted influence on inflammation, OS, and neuroendocrine regulation. Additionally, we discuss the clinical application prospects of BDNF in disease diagnosis and treatment, as well as progress in related drug development. A deeper understanding of BDNF’s role in the heart-brain axis will provide new insights and strategies for the prevention, diagnosis, and treatment of CVDs and MD.

PMID:40299045 | DOI:10.1007/s00406-025-02016-w