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Cosegregation of Gastrointestinal Ulcers and Schizophrenia in a Large National Inpatient Discharge Database
  1. Vural Ozdemir,
  2. Mazen M. Jamal,
  3. Klara Osapay,
  4. Martin R. Jadus,
  5. Zsuzsanna Sandor,
  6. Mehrtash Hashemzadeh,
  7. Sandor Szabo
  1. From the Department of Preventive and Social Medicine (V.O.), Bioethics Programs, Faculty of Medicine, University of Montreal, Montreal, QC; and VA Long Beach Medical Center (M.M.J., K.O., M.R.J., Z.S., M.H., S.S.), Long Beach, CA.
  1. Dr. Ozdemir is the recipient of an ethics operating grant from the Canadian Institutes of Health Research. The study was in part supported by intramural research funds from the VA Long Beach Medical Center.
  2. Address correspondence to: Dr. Vural Ozdemir, Bioethics Programs, Department of Preventive and Social Medicine, Faculty of Medicine, University of Montreal, 3333 Queen Mary, Suite 610-8, Montreal, QC H3V 1A2; e-mail: m.vural.ozdemir{at}

Revisiting the “Brain-Gut Axis” Hypothesis in Ulcer Pathogenesis


The lifetime prevalence of duodenal ulcer in the United States is 8 to 10%, whereas another 1% of the population is affected by gastric ulcer. Both central and peripheral dopamine pathways may influence ulcer pathogenesis. Dopamine agonists prevent whereas antagonists augment stress- and chemically induced gastrointestinal ulcers in preclinical models. The dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,36-tetrahydropyridine (MPTP) depletes central dopamine and induces lesions in the substantia nigra, and, if given in high doses, MPTP induces a Parkinson disease-like syndrome and gastric ulcers. Because schizophrenia is attributed, in part, to an overactive dopaminergic system, persons with schizophrenia may display a reduced susceptibility toward gastrointestinal ulcers.

A case-control study was conducted in patients represented in the 2002 National Inpatient Sample, the largest all-payer inpatient care database in the United States, consisting of 5 to 8 million inpatient hospital stays per year, which approximates a 20% sample of community hospitals.

A significant association was observed between schizophrenia and diminished risk for duodenal (odds ratio [OR] 0.55; 95% confidence interval [CI] 0.45-0.67) and gastric (OR 0.54; 95% CI 0.46-0.63) (p < .01) ulcers but not for gastrojejunal ulcers (OR 0.44; 95% CI 0.16-1.20) (p = .11). Potential confounders such as age, gender, race, tobacco or alcohol dependence, and Helicobacter pylori infection were controlled in multivariate analyses.

This observational study in a large sample of patients in community hospitals suggests that schizophrenia and attendant neurobiologic mechanisms (eg, variability in dopamine pathways) may act in concert to modify the composite risk for gastrointestinal ulcers. Dopamine pathways warrant further prospective research as new potential drug targets in ulcer disease.

Key words
  • schizophrenia
  • gastrointestinal ulcer
  • association study
  • dopamine
  • naturalistic design
  • brain-gut axis
  • drug targets

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