Abstract
BACKGROUND: The intricate pathophysiological mechanisms of major depressive disorder (MDD) necessitate the development of comprehensive early indicators that reflect the complex interplay of emotional, physical, and cognitive factors. Despite its potential to fulfill these criteria, interoception remains underexplored in MDD. This study aimed to evaluate the potential of interoception in transforming MDD's clinical practices by examining interoception deficits across various MDD stages and analyzing their complex associations with the spectrum of depressive symptoms. METHODS: This study included 431 healthy individuals, 206 subclinical depression individuals, and 483 MDD patients. Depressive symptoms and interoception function were assessed using the PHQ-9 and MAIA-2, respectively. RESULTS: Interoception dysfunction occurred in the preclinical phase of MDD and further impaired in the clinical stage. Antidepressant therapies showed limited efficacy in improving interoception and might damage some dimensions. Interoceptive dimensions might predict depressive symptoms, primarily enhancing negative thinking patterns. The predictive model based on interoception was built with random split verification and demonstrated good discrimination and predictive performance in identifying MDD. CONCLUSIONS: Early alterations in the preclinical stage, multivariate associations with depressive symptoms, and good discrimination and predictive performance highlight the importance of interoception in MDD management, pointing to a paradigm shift in diagnostic and therapeutic approaches.