Research Progress on the Pathogenesis of Post-Stroke Depression

Abstract

Poststroke depression (PSD) is a common neuropsychiatric complication following stroke. Clinically, it is characterized by persistent low mood, cognitive dysfunction, and somatic symptoms, which severely impact the recovery and quality of life of stroke patients, making it an urgent issue in clinical practice. Currently, the pathogenesis of PSD remains incompletely understood. This study presents a narrative review of the literature from PubMed, Web of Science, and CNKI, with a particular focus on research conducted between 2021 and 2025. The findings reveal that advancements in neuroscience, immunology, and gut microbiome studies have contributed to important breakthroughs in understanding the mechanisms underlying PSD, such as the interaction between the hypothalamic–pituitary–adrenal (HPA) axis and neuroinflammation. In terms of treatment, several novel approaches have emerged. Traditional Chinese medicine (TCM) has attracted increasing attention due to its low cost, high safety, and minimal side effects. Herbal formulas have shown promising therapeutic effects for PSD. Moreover, combination therapies, such as acupuncture combined with repetitive transcranial magnetic stimulation (rTMS), have been demonstrated to be more effective than monotherapies. This review summarizes the multidimensional pathophysiology of PSD, including neurotransmitter imbalance, neuroinflammation, impaired neuroplasticity, structural brain damage, HPA axis dysregulation, gut-brain axis imbalance, and psychosocial factors. Additionally, current clinical treatment strategies for PSD are reviewed, with the aim of providing a theoretical foundation for early diagnosis, timely intervention, the development of novel anti-PSD therapies, and the establishment of more comprehensive treatment strategies for PSD.