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Unmedicated individuals with major depressive disorder (MDD) show abnormal interoception, but it is unclear whether antidepressant treatment via serotonergic medication alters this relationship. The current cross-sectional study examined associations between neural and behavioral indices of interoceptive processing and chronic serotonergic medication administration in MDD. 47 selective serotonin reuptake inhibitor (SSRI)-medicated MDD (MDD-SSRI) individuals were propensity-matched with 48 unmedicated current MDD (MDD-UnMed) and 41 healthy comparison (HC) participants on demographics including age, sex, body mass index, education, as well as on dimensional scales of symptom severity including depression and anxiety. All participants completed an interoceptive attention task during functional magnetic resonance imaging, and a behavioral heartbeat tapping task under three conditions: Guessing, No Guessing, and Breath Hold. Relative to HC, both MDD groups: (1) exhibited lower mid-insula, amygdala, putamen, and caudate activation during interoceptive versus exteroceptive attention; and (2) showed poorer heartbeat tapping performance during the Breath Hold condition. However, the MDD-SSRI group reported higher intensity ratings of heartbeat and stomach sensations than MDD-UnMed and HC during the interoceptive attention task. These findings suggest that the attenuated patterns of neural activation observed in depressed individuals during interoceptive attention are not ameliorated by the chronic administration of serotonergic medications. However, amplified interoceptive sensation ratings suggest a potential impact of chronic serotonergic medication on conscious experiences of internal body states. Future investigations will need to determine the extent to which serotonergic medications acutely influence interoceptive processing, and whether such changes play a role in therapeutic responses during treatment initiation.
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