title: Attention-deficit/hyperactivity disorder, methylphenidate use and the risk of developing schizophrenia spectrum disorders: A nationwide population-based study in Taiwan.
abstract: This study estimated the risk of developing psychotic disorders by comparing children with ADHD to non-ADHD controls, and to examine whether methylphenidate (MPH) treatment influences the risks of psychotic disorders. A nationwide cohort of patients who were newly diagnosed with ADHD (n=73,049) and age- and gender-matched controls (n=73,049) were selected from Taiwan's National Health Insurance database from January 2000 to December 2011. All participants were observed until December 31, 2011. Cox regression models were used to estimate the effects of ADHD diagnosis and MPH use on subsequent outcomes. Having a diagnosis of any psychotic disorder and of schizophrenia were set as two different outcomes and were analyzed separately. Compared to the control group, the ADHD group showed significantly increased risk of developing any psychotic disorder (adjusted hazard ratio [aHR], 5.20; 95% confidence interval [CI], 4.30-6.30) and schizophrenia (aHR, 4.65; 95% CI, 3.59-6.04). Compared to ADHD patients without psychosis, patients with ADHD who developed psychosis had significantly older age at first diagnosis of ADHD (9.4±3.3years vs. 10.6±4.0years). Among patients with ADHD, MPH use significantly increased the risk of developing any psychotic disorder (aHR, 1.20; 95% CI, 1.04-1.40), but did not increase the risk of developing schizophrenia (aHR, 1.16; 95% CI, 0.94-1.42). The results indicated that previous diagnoses of ADHD are a powerful indicator of developing psychotic disorders. Nevertheless, the specific mechanisms of the relationships between ADHD, MPH use and psychotic disorders need further elucidation in future clinical studies.
authors.affiliation: Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan.
authors.forename: Yu-Chiau
authors.initials: YC
authors.lastname: Shyu
authors.affiliation: Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
authors.forename: Shin-Sheng
authors.initials: SS
authors.lastname: Yuan
authors.affiliation: Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Sheng-Yu
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan; Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Chun-Ju
authors.initials: CJ
authors.lastname: Yang
authors.affiliation: Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei, Taiwan; Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
authors.forename: Kang-Chung
authors.initials: KC
authors.lastname: Yang
authors.affiliation: Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States.
authors.forename: Tung-Liang
authors.initials: TL
authors.lastname: Lee
authors.affiliation: Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: wangliangjen@gmail.com.
authors.forename: Liang-Jen
authors.initials: LJ
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000453:epidemiology*; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011618:Psychotic Disorders / Q000453:epidemiology*; D012306:Risk; D012559:Schizophrenia / Q000453:epidemiology*; D016019:Survival Analysis; D013624:Taiwan / Q000453:epidemiology
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate
keywords: ADHD; Cohort study; Epidemiology; Psychosis; Stimulant