Interactive Effects of Early-Life Stress, Diet, and Metabolism on Gastrointestinal Dysfunction With Neuropsychiatric Symptoms

The study population comprises adults aged 18-65 years of any sex. A total of 200 participants are planned: 100 cases with functional dyspepsia, gastroparesis, or irritable bowel syndrome, gastrointestinal symptoms lasting at least 3 months, and psychological symptoms or stress-related questionnaire scores meeting the protocol-defined thresholds; and 100 controls undergoing routine health examinations, without a history of these gastrointestinal disorders or chronic gastrointestinal symptoms, with depression and anxiety scores below the specified thresholds and no significant endoscopic abnormalities. Age and sex will be matched between groups where feasible. All participants must meet the eligibility criteria and provide written informed consent.

Inclusion Criteria:

-

Case Group:

1. Adults aged 18-65 years, of any sex.
2. Functional dyspepsia, gastroparesis, or irritable bowel syndrome, with gastrointestinal symptoms lasting at least 3 months. Relevant symptoms include nausea, vomiting, postprandial fullness, early satiety, and bloating.
3. At least one of the following psychological or stress-related criteria: Patient Health Questionnaire-9 (PHQ-9) score ≥5; 17-item Hamilton Depression Rating Scale (HAMD-17) score ≥8; Self-Rating Anxiety Scale (SAS) score ≥50; Hamilton Anxiety Rating Scale (HAMA) score ≥7; Childhood Trauma Questionnaire (CTQ) total score ≥40; or Adolescent Self-Rating Life Events Checklist (ASLEC) total score ≥30.
4. Upper gastrointestinal endoscopy and colonoscopy excluding organic gastrointestinal lesions, such as peptic ulcers, gastrointestinal tumors, or esophageal strictures.
5. Voluntary participation and provision of written informed consent.

Control Group:

1. Adults aged 18-65 years, of any sex, with age and sex matched to the case group where feasible.
2. No history of functional dyspepsia, gastroparesis, or irritable bowel syndrome, and no chronic gastrointestinal symptoms, such as recurrent abdominal pain, bloating, nausea, or vomiting.
3. All of the following: PHQ-9 score <5, HAMD-17 score <8, SAS score <50, and HAMA score <7.
4. Undergoing routine health examinations, with no significant abnormalities on upper gastrointestinal endoscopy and colonoscopy.
5. Voluntary participation and provision of written informed consent.

Exclusion Criteria:

-

The following exclusion criteria apply to both groups:

1. Severe underlying disease, including severe hepatic or renal dysfunction (ALT/AST >3 times the upper limit of normal or serum creatinine >133 μmol/L), malignancy, severe coronary artery disease, or heart failure.
2. Diagnosed organic gastrointestinal disease, including peptic ulcers, gastrointestinal tumors, inflammatory bowel disease, or intestinal obstruction.
3. Previous gastrointestinal resection, except appendectomy.
4. Use within the past month of medications affecting gastrointestinal motility, such as opioids, anticholinergics, or prokinetic agents, or medications substantially affecting metabolism, such as statins or systemic corticosteroids.
5. Diagnosed severe psychiatric disorders, such as schizophrenia or bipolar disorder, or a suicide attempt or suicidal behavior within the past 6 months.
6. Pregnancy or breastfeeding.
7. Inability to understand the questionnaires or cooperate with completion of the assessments.