BACKGROUND: Social support is recognized as a critical factor in both the prevention and management of Major depression Disorder (MDD), and can influence interoceptive processes. The mechanism of sex differences in the association between social support and MDD has not been clarified. This study was to elucidate the mechanism of sex differences in the association between social support and MDD by a mediation analysis with interoception mediator. METHODS: Participants included 390 depressed patients (male/female: 150/240). Social Support Rating Scale (SSRS) was used to assess the degree of social support
Multidimensional Assessment of Interoceptive Awareness (MAIA-2C) was used to evaluate the interoception
Patient Health Questionnaire-9 (PHQ-9) was used to assess depression status. The pairwise correlated variables were put into the mediation model for the mediation analysis. RESULTS: The depression status in female depressed patients was more severity than that in male depressed patients, while the social support in female depressed patients was less than that in male depressed patients. In male depressed patients, the Noticing of MAIA-2C plays a partial mediating role in social support and depression status, however, in female depressed patients, the Self-Regulation and Trusting of MAIA-2C plays a partial mediating role in social support and depression status. CONCLUSIONS: The female depressed patients receive significantly less social support than male counterparts, contributing to more severe symptoms, with the quality and adequacy of social support being crucial due to its mediation by interoception, highlighting a biological mechanism behind MDD. Differences in how interoception mediating role between genders suggest a physiological reason for the heightened severity of depressive symptoms in females.