Histidine Decarboxylase Deficiency Causes Tourette Syndrome: Parallel Findings in Humans and Mice

Lissandra Castellan Baldan, Kyle A. Williams, Jean Dominique Gallezot, Vladimir Pogorelov, Maximiliano Rapanelli, Michael Crowley, George M. Anderson, Erin Loring, Roxanne Gorczyca, Eileen Billingslea, Suzanne Wasylink, Kaitlyn E. Panza, A. Gulhan Ercan-Sencicek, Kuakarun Krusong, Bennett L. Leventhal, Hiroshi Ohtsu, Michael H. Bloch, ZoëA Hughes, John H. Krystal, Linda MayesIvan deAraujo, Yu Shin Ding, Matthew W. State, Christopher Pittenger

Research output: Contribution to journalArticlepeer-review

154 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)77-90
Number of pages14
Issue number1
Publication statusPublished - 2014 Jan 8

ASJC Scopus subject areas

  • Neuroscience(all)


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