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 CITALOPRAM’S 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. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT06212284 ### Funding Statement This study was funded by the School of Psychology, University of Sussex. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Research Governance and Ethics CommitteeThe Cross-Schools Research Ethics Committee of the Brighton and Sussex Medical School gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. Summary data is available at DOI 10.6084/m9.figshare.22786274.