Patients with
gastroesophageal reflux disease (
GERD) can present with typical or atypical symptoms. The aim of this study is to explore the underlying physiological and psychological mechanisms that lead to different symptomatic manifestations of
GERD. A total of 238 patients diagnosed with
GERD underwent gastroscopy, 24 h multichannel intraluminal impedance-pH (MII-pH) monitoring, and psychological assessment with questionnaires. Patient symptoms were used to classify
GERD into phenotypes of typical reflux syndrome (TRS, n = 87), reflux
chest pain syndrome (RCS, n = 98), and extraesophageal syndromes (EES, n = 53). 38 healthy volunteers served as controls. Reflux parameters and baseline impedance values (BIVs) were acquired from MII-pH monitoring results. A subset of subjects were biopsied from the lower esophagus; certain immune cells were stained with immunohistochemistry. BIVs in
GERD patients (TRS, RCS, and EES) were significantly lower than in healthy controls and TRS patients exhibited the lowest BIVs (all P < 0.01). This indicated that the extent of mucosal injury differed across groups. TRS patients had higher
acid exposure time (
AET) compared to RCS, EES and controls (all P < 0.05). RCS patients had more intraepithelial T lymphocyte (IEL) and mast cell (MC) infiltration, and higher psychometric scores compared to TRS patients and controls (all P < 0.05), suggesting a possible stress-related esophageal
hypersensitivity basis. TRS patients are characterized by
acid reflux and correlated mucosal injury, which explains their typical reflux symptoms. RCS patients exhibit less
acid-related injury but possible psychological stress-related esophageal
hypersensitivity, which could be the main cause of their esophageal
pain.