Mast cells and corticotropin-releasing hormone receptors in duodenal tissue of children with functional dyspepsia.

Objectives: Functional dyspepsia (FD) is a disorder of the gut-brain interaction characterized by epigastric pain, nausea, and/or early satiety. Existing literature suggests a physical link between psychiatric diagnoses and disorders of the gut-brain interaction at intestinal mast cells (MC) via corticotropin-releasing hormone (CRH) and its intestinally located receptors (CRHR1/CRHR2). Our study aimed to further clarify the physiologic connection between pediatric psychiatric illness and FD.

Methods: Study subjects were identified and classified into three groups. The FD group met Rome IV criteria and had insignificant gross endoscopic and histologic findings on gastric and duodenal biopsies. The control group reported no gastrointestinal symptoms or documented psychiatric illness. A third group consisted of Helicobacter pylori (HP)-positive dyspepsia patients independent of psychiatric history. Duodenal biopsy blocks were stained with antibodies targeting MCs, CRH, and CRHR1/CRHR2.

Results: We included 49 patients: 21 FD, nine controls, and 19 HP patients. We found a statistical difference between duodenal MC density in FD versus controls and HP versus controls (p < 0.05). We found no significant CRHR2 staining in the control group, yet the FD and HP groups yielded strong stains. We found a significant increase in MC density and CRHR2 staining in patients with a psychiatric history versus without (p < 0.05).

Conclusion: Our data show increased MC density and stronger CRHR2 staining in patients with FD and in patients with a psychiatric history. Our data support a pathophysiologic theory of FD development via a "gut-brain axis" intersecting at the level of MCs with influence via peripheral CRH.