General and Anxiety-Linked Influence of Acute Serotonin Reuptake Inhibition on Neural Responses Associated with Attended Visceral Sensation

Serotonin is known to have state-dependent modulatory influences on exteroceptive sensory processes and the processing of pain, but much less is known about its role in ordinary interoceptive processes and their relationships to affective states. This experiment compared the impact of a selective serotonin reuptake inhibitor (SSRI) (20mg CITALOPRAM), acutely increasing extracellular serotonin, to that of a PLACEBO on the neural processing of ordinary interoceptive sensations and the relationship of these influences to anxious states. Twenty-one healthy young volunteers completed the visceral interoceptive attention (VIA) task with each treatment, focusing attention on heart, stomach, or visual sensation control while scanned with functional magnetic resonance imaging (fMRI). The relative neural interoceptive response (IR) to heart sensation [heart minus visual] and stomach sensation [stomach minus visual] were compared between treatment conditions, controlling for general effects on sensory processing. CITALOPRAM reduced interoceptive processing in viscerosensory (bilateral posterior insular cortex, stomach-IR) and integrative/affective components (bilateral amygdala, stomach-IR and heart-IR) of known interoceptive pathways. We then searched for state-dependent modulatory effects of CITALOPRAM that varied with current levels of anxiety. The anterior insular cortex response to heart sensation increased with anxiety, replicating prior findings. This relationship disappeared on CITALOPRAM. Preliminary post hoc exploration found that CITALOPRAMS effects on amygdalae response to stomach sensation predicted acute increases and decreases in anxiety. Overall, this evidence of general and state-dependent serotonergic influence advances our understanding of interoception, its regulation, and its relationship to anxious states.