Format

Send to:

Choose Destination
See comment in PubMed Commons below
Neuron. 2014 Jan 8;81(1):77-90. doi: 10.1016/j.neuron.2013.10.052.

Histidine decarboxylase deficiency causes tourette syndrome: parallel findings in humans and mice.

Author information

  • 1Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 2Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA; Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 3Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 4Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 5Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 6Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Program on Neurogenetics, Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 7Neuroscience Research Unit, Pfizer, Inc., Cambridge, MA 02139, USA.
  • 8Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 9Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
  • 10Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; Department of Child and Adolescent Psychiatry, New York University/NYU Langone Medical Center, New York, NY 10016, USA.
  • 11Graduate School of Engineering, Tohoku University, Sendai 980-8577, Japan.
  • 12Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA; Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Psychology, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 13Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA; John B. Pierce Laboratory, New Haven, CT 06519, USA.
  • 14Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA; Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Program on Neurogenetics, Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 15Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA; Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Psychology, Yale University School of Medicine, New Haven, CT 06520, USA; Integrated Neuroscience Research Program, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: christopher.pittenger@yale.edu.

Erratum in

  • Neuron. 2014 Jun 4;82(5):1186-7.

Abstract

Tourette syndrome (TS) is characterized by tics, sensorimotor gating deficiencies, and abnormalities of cortico-basal ganglia circuits. A mutation in histidine decarboxylase (Hdc), the key enzyme for the biosynthesis of histamine (HA), has been implicated as a rare genetic cause. Hdc knockout mice exhibited potentiated tic-like stereotypies, recapitulating core phenomenology of TS; these were mitigated by the dopamine (DA) D2 antagonist haloperidol, a proven pharmacotherapy, and by HA infusion into the brain. Prepulse inhibition was impaired in both mice and humans carrying Hdc mutations. HA infusion reduced striatal DA levels; in Hdc knockout mice, striatal DA was increased and the DA-regulated immediate early gene Fos was upregulated. DA D2/D3 receptor binding was altered both in mice and in humans carrying the Hdc mutation. These data confirm histidine decarboxylase deficiency as a rare cause of TS and identify HA-DA interactions in the basal ganglia as an important locus of pathology.

Copyright © 2014 Elsevier Inc. All rights reserved.

PMID:
24411733
[PubMed - indexed for MEDLINE]
PMCID:
PMC3894588
Free PMC Article

Publication Types, MeSH Terms, Substances, Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk