Underlying Mechanisms of Comorbidity between Chronic Cough and Depression: A Review

There is a complex bidirectional association between chronic cough and depression, which constitutes a significant medical challenge. Epidemiological studies have shown that the incidence of depression in patients with chronic cough is as high as 33-53%, while the risk of new-onset chronic cough is significantly increased in patients with depression. Specifically, the risk of cough in individuals with severe depression is 3.32 times than those without depressive symptoms. Pathophysiological mechanisms underlying this bidirectional association include the following. From the perspective of neural pathways, the cough reflex and emotional regulation share neural pathways, including the vagus nerve, brainstem, limbic system, prefrontal cortex, and other brain regions. Both patients with chronic cough and depression exhibit abnormal functional connectivity and remodeling of the aforementioned neural pathways, as well as imbalanced levels of key neurotransmitters such as serotonin, glutamate, and γ-aminobutyric acid. From the perspective of the immune-inflammatory dimension, chronic inflammatory mediators such as IL-6 and TNF-α form a vicious cycle between peripheral inflammation and central inflammation, further exacerbating the comorbidity process. Elucidating the pathophysiological mechanism of this bidirectional association is of great theoretical and practical significance for optimizing clinical diagnosis and treatment strategies for comorbid patients, as well as improving their prognosis.