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Increased risk of diseases of the basal ganglia and cerebellum in patients with a history of attention-deficit/hyperactivity disorder

Neuropsychopharmacology (2018) | Download Citation


Attention-deficit/hyperactivity disorder (ADHD) is marked by an ongoing pattern of inattention and/or hyperactivity and involves dysregulated dopaminergic pathways. Dopaminergic agents (i.e., amphetamine and methylphenidate) are thus prescribed to treat ADHD. As little is known regarding long-term consequences of either ADHD or its treatment, the objective of this study was to determine if either alters the risk of diseases of the basal ganglia and cerebellum, including Parkinson’s disease. Statewide medical records from 1996 to 2016 were retrieved from the Utah Population Database to conduct a retrospective cohort study. Participants included ADHD patients (International Classification of Diseases, 9th version (ICD-9) diagnosis codes 314.0–314.2, 314.8, 314.9) and 5:1 random sex-matched and age-matched subjects with no ADHD diagnosis history. Both patients and non-ADHD subjects met the following eligibility criteria: (1) no prior diagnosis of Parkinson’s disease, secondary parkinsonism, basal ganglia disease, or essential tremor (ICD-9 codes 332.0, 332.1, 333.0, 333.1), (2) born in 1950 or later and age ≥20 years at last follow-up, and (3) no history of substance abuse (illicit drugs or alcohol). Outcomes were measured as time to diagnosis of diseases of the basal ganglia and cerebellum, death, or study-end. A Cox model incorporating a competing risk of death was used to provide hazard ratio estimates. Patients with ADHD (N = 31,769) had a 2.4-fold increased risk of basal ganglia and cerebellum diseases (95% confidence interval (CI): 2.0–3.0; P < 0.0001) compared with 158,790 non-ADHD persons, after controlling for sex and age and adjusting for tobacco use and psychotic conditions. In 4960 ADHD patients prescribed psychostimulants, risk of basal ganglia and cerebellum diseases between ages 21 and 49 years was especially pronounced, at 8.6-fold (95% CI: 4.8–15.6; P < 0001). The association of ADHD patients prescribed psychostimulants with higher risk of diseases of the basal ganglia and cerebellum may reflect a more severe ADHD phenotype rather than a direct association between prescribed stimulant use and basal ganglia or cerebellum disorders. Future studies to assess and stratify patient risk so as to inform treatment are warranted.

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We gratefully acknowledge the thoughtful insights and suggestions of Dr. Kathleen Ries Merikangas, Ph.D., and Senior Investigator and Chief, Genetic Epidemiology Research Branch with the National Institute of Mental Health Intramural Research Program in the preparation of this manuscript. We thank the Pedigree and Population Resource, Huntsman Cancer Institute, at the University of Utah (funded in part by the Huntsman Cancer Foundation) for its role in the ongoing collection, maintenance and support of the UPDB. We acknowledge the University of Utah’s Information Technology Services and Biomedical Informatics Core for establishing the Master Subject Index between the UPDB, University of Utah Health Care, and Intermountain Healthcare; without their institutional support, this study would not be possible. Supported by DA031833, DA039145 and the Huntsman Cancer Foundation. The UPDB is partially supported by P30-CA042014, the University of Utah’s Program in Personalized Health and Center for Clinical and Translational Science, and NCRR R01-RR021746. The support for this study was provided by National Institute on Drug Abuse grants DA031833 (to G.R.H.) and DA039145 (to A.E.F.). Partial support for the UPDB was provided by: National Cancer Institute P30 CA2014; the University of Utah’s Program in Personalized Health and Center for Clinical and Translational Science (funded by NIH Clinical and Translational Science Awards); and a National Center for Research Resources grant, “Sharing Statewide Health Data for Genetic Research” (RR021746 to G. Mineau) with additional support from the Utah State Department of Health.

Author information


  1. Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA

    • Karen Curtin
  2. University of Utah School of Dentistry, Salt Lake City, UT, USA

    • Annette E. Fleckenstein
    •  & Glen R. Hanson
  3. Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA

    • Brooks R. Keeshin
  4. Department of Pediatric Psychiatry, Intermountain Healthcare Primary Children’s Hospital, Salt Lake City, UT, USA

    • Brooks R. Keeshin
  5. Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA

    • Deborah A. Yurgelun-Todd
    •  & Perry F. Renshaw
  6. Human Development and Family Studies, University of Utah, Salt Lake City, UT, USA

    • Ken R. Smith


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The authors declare no competing interest.

Corresponding author

Correspondence to Glen R. Hanson.

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