Abstract: Objective To explore the comorbidity mechanism of asthma and depression. Methods A self-developed questionnaire, which also contained Asthma Control Test (ACT), Asthma Quality of Life Questionnaire (AQLQ) and Hamilton Rating Scale for depression (HRSD), was administered in 41 participants with asthma (AS), asthma and depression (AD), or none any of these conditions (health control, HC). Lung function and blood levels of eosnophils and IgE were also detected in those in the AS and AD groups. Blood CD4+ T cells were isolated in all of the participants to extract RNA for reverse transcription to cDNA. Real-time polymerase chain reaction (RT-PCR) was performed using cDNA as a template to detected the expression levels of HTR1A, HTR2A, HTR7, SLC6A4, and B2M genes. Results Participants with AS and AD had lower expression level ofSLC6A4 than the healthy controls ( P=0.000). The expression level of HTR2Ain participants with AS was lower than that in the healthy controls ( P=0.021) and marginally lower than that in participants with AD ( P=0.077). Participants with AD had lower AQLQ scores than participants with AS ( P=0.004). Conclusion Asthma and depression is correlated at gene level. Decreased expression ofSLC6A4gene may be one of the possible comorbidity mechanisms of asthma and depression.