TY - JOUR
T1 - Histidine Decarboxylase Deficiency Causes Tourette Syndrome
T2 - Parallel Findings in Humans and Mice
AU - Castellan Baldan, Lissandra
AU - Williams, Kyle A.
AU - Gallezot, Jean Dominique
AU - Pogorelov, Vladimir
AU - Rapanelli, Maximiliano
AU - Crowley, Michael
AU - Anderson, George M.
AU - Loring, Erin
AU - Gorczyca, Roxanne
AU - Billingslea, Eileen
AU - Wasylink, Suzanne
AU - Panza, Kaitlyn E.
AU - Ercan-Sencicek, A. Gulhan
AU - Krusong, Kuakarun
AU - Leventhal, Bennett L.
AU - Ohtsu, Hiroshi
AU - Bloch, Michael H.
AU - Hughes, ZoëA
AU - Krystal, John H.
AU - Mayes, Linda
AU - deAraujo, Ivan
AU - Ding, Yu Shin
AU - State, Matthew W.
AU - Pittenger, Christopher
N1 - Funding Information:
We thank Stacey Wilber for assistance with mouse genotyping; Theresa Brand for assistance with HA analysis in tissue; the staff of the Yale PET Center for support in all PET studies and analyses; Brian Pittman for statistical consultation and support; and Marina Picciotto, Ronald Duman, and Ralph DiLeone for helpful discussion and comments on the manuscript. This work was supported by The Allison Family Foundation (C.P.) and National Institutes of Health grants K08MH081190 (C.P.), R01MH091861 (C.P.), PL1DA024860 (G.M.A.), R01NS056276 (M.W.S.), T32MH014276 (L.C.B.; Principal Investigator (PI), R. Duman), T32MH018268 (K.A.W.; PI, J. Leckman), UL1RR024139 (Yale Center for Clinical Investigation Pilot Award to C.P.; PI, R. Sherwin), 2P50AA012870 (J.H.K.), and D43TW06166 (K.K.; PIs, J. Gelertner and R. Malison). Additional support came from the Tourette Syndrome Association (C.P., L.C.B.); the Yale Program on Neurogenetics (A.G.E.S., M.W.S.); the Yale PET Center (Y.-S.D., J.-D.G.); the Brain Research Foundation, Chicago, IL; the Overlook International Fund; Pfizer Global Research (R.G., Z.A.H.); and the State of Connecticut through its support of the Ribicoff Research Facilities at the Connecticut Mental Health Center (C.P., L.C.B., V.P., M.R.). Z.A.H. and R.G. are employees of Pfizer, Inc.
PY - 2014/1/8
Y1 - 2014/1/8
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84891760813
U2 - 10.1016/j.neuron.2013.10.052
DO - 10.1016/j.neuron.2013.10.052
M3 - Article
C2 - 24411733
AN - SCOPUS:84891760813
SN - 0896-6273
VL - 81
SP - 77
EP - 90
JO - Neuron
JF - Neuron
IS - 1
ER -