title: Gastroesophageal reflux disease and risk for bipolar disorder: a nationwide population-based study.
abstract: BACKGROUND
  Studies have shown that chronic inflammation may play a vital role in the pathophysiology of both gastroesophageal reflux disease (GERD) and bipolar disorder. Among patients with GERD, the risk of bipolar disorder has not been well characterized.
  
  
  OBJECTIVE
  We explored the relationship between GERD and the subsequent development of bipolar disorder, and examined the risk factors for bipolar disorder in patients with GERD.
  
  
  METHODS
  We identified patients who were diagnosed with GERD in the Taiwan National Health Insurance Research Database. A comparison cohort without GERD was matched according to age, sex, and comorbidities. The occurrence of bipolar disorder was evaluated in both cohorts based on diagnosis and the prescription of medications.
  
  
  RESULTS
  The GERD cohort consisted of 21,674 patients, and the comparison cohort consisted of 21,674 matched control patients without GERD. The incidence of bipolar disorder (incidence rate ratio [IRR] 2.29, 95% confidence interval [CI] 1.58-3.36, P<.001) was higher among GERD patients than among comparison cohort. Multivariate, matched regression models showed that the female sex (hazard ratio [HR] 1.78, 95% CI 1.76-2.74, P = .008), being younger than 60 years old (HR 2.35, 95% CI 1.33-4.16, P = .003), and alcohol use disorder (HR 4.89, 95% CI 3.06-7.84, P = .004) were independent risk factors for the development of bipolar disorder among GERD patients.
  
  
  CONCLUSIONS
  GERD may increase the risk of developing bipolar disorder. Based on our data, we suggest that attention should be focused on female patients younger than 60 years, and patients with alcohol use disorder, following a GERD diagnosis.
authors.affiliation: Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Wan-Shan
authors.initials: WS
authors.lastname: Lin
authors.affiliation: Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Institute of Public Health, National Yang-Ming University, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Hu
authors.affiliation: Institute of Public Health, National Yang-Ming University, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chia-Jen
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Chih-Chao
authors.initials: CC
authors.lastname: Hsu
authors.affiliation: Department of Psychiatry, Chiayi Branch, Taichung Veterans General Hospital, Taipei, Taiwan.
authors.forename: Cheng-Che
authors.initials: CC
authors.lastname: Shen
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan; Endoscopy Center of Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yen-Po
authors.initials: YP
authors.lastname: Wang
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan; Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Hu
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chia-Fen
authors.initials: CF
authors.lastname: Tsai
authors.affiliation: Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chiu-Mei
authors.initials: CM
authors.lastname: Yeh
authors.affiliation: Department of Psychiatry, Su-Ao and Yuanshan Branch, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Pan-Ming
authors.initials: PM
authors.lastname: Chen
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Tung-Ping
authors.initials: TP
authors.lastname: Su
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Tzeng-Ji
authors.initials: TJ
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Ti
authors.initials: T
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000150:complications*; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications* / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology