Mechanisms of dopaminergic and serotonergic neurotransmission in Tourette syndrome: clues from an in vivo neurochemistry study with PET

Dean F Wong; James R Brasic; Harvey S Singer; David J Schretlen; Hiroto Kuwabara; Yun Zhou; Ayon Nandi; Marika A Maris; Mohab Alexander; Weiguo Ye; Olivier Rousset; Anil Kumar; Zsolt Szabo; Albert Gjedde; Anthony A Grace

doi:10.1038/sj.npp.1301528

Mechanisms of dopaminergic and serotonergic neurotransmission in Tourette syndrome: clues from an in vivo neurochemistry study with PET

Dean F Wong, James R Brasic, Harvey S Singer, David J Schretlen, Hiroto Kuwabara, Yun Zhou, Ayon Nandi, Marika A Maris, Mohab Alexander, Weiguo Ye, Olivier Rousset, Anil Kumar, Zsolt Szabo, Albert Gjedde, Anthony A Grace

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

216 Citationer (Scopus)

Abstract

Udgivelsesdato: 2008-May

Originalsprog	Engelsk
Tidsskrift	Neuropsychopharmacology
Vol/bind	33
Udgave nummer	6
Sider (fra-til)	1239-51
Antal sider	12
ISSN	0893-133X
DOI	https://doi.org/10.1038/sj.npp.1301528
Status	Udgivet - 2007
Udgivet eksternt	Ja

Bibliografisk note

Keywords: Adult; Amphetamine; Brain Mapping; Dopamine; Dopamine Agents; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Magnetic Resonance Imaging; Male; Models, Theoretical; Neuropsychological Tests; Obsessive-Compulsive Disorder; Positron-Emission Tomography; Psychiatric Status Rating Scales; Raclopride; Receptors, Dopamine D2; Serotonin; Synaptic Transmission; Tourette Syndrome

Adgang til dokumentet

10.1038/sj.npp.1301528

Citationsformater

Wong, D. F., Brasic, J. R., Singer, H. S., Schretlen, D. J., Kuwabara, H., Zhou, Y., Nandi, A., Maris, M. A., Alexander, M., Ye, W., Rousset, O., Kumar, A., Szabo, Z., Gjedde, A., & Grace, A. A. (2007). Mechanisms of dopaminergic and serotonergic neurotransmission in Tourette syndrome: clues from an in vivo neurochemistry study with PET. Neuropsychopharmacology, 33(6), 1239-51. https://doi.org/10.1038/sj.npp.1301528

Wong, DF, Brasic, JR, Singer, HS, Schretlen, DJ, Kuwabara, H, Zhou, Y, Nandi, A, Maris, MA, Alexander, M, Ye, W, Rousset, O, Kumar, A, Szabo, Z, Gjedde, A & Grace, AA 2007, 'Mechanisms of dopaminergic and serotonergic neurotransmission in Tourette syndrome: clues from an in vivo neurochemistry study with PET', Neuropsychopharmacology, bind 33, nr. 6, s. 1239-51. https://doi.org/10.1038/sj.npp.1301528

@article{1e559a908a6911df928f000ea68e967b,

title = "Mechanisms of dopaminergic and serotonergic neurotransmission in Tourette syndrome: clues from an in vivo neurochemistry study with PET",

abstract = "Tourette syndrome (TS) is a neuropsychiatric disorder with childhood onset characterized by motor and phonic tics. Obsessive-compulsive disorder (OCD) is often concomitant with TS. Dysfunctional tonic and phasic dopamine (DA) and serotonin (5-HT) metabolism may play a role in the pathophysiology of TS. We simultaneously measured the density, affinity, and brain distribution of dopamine D2 receptors (D2-R's), dopamine transporter binding potential (BP), and amphetamine-induced dopamine release (DA(rel)) in 14 adults with TS and 10 normal adult controls. We also measured the brain distribution and BP of serotonin 5-HT2A receptors (5-HT2AR), and serotonin transporter (SERT) BP, in 11 subjects with TS and 10 normal control subjects. As compared with controls, DA rel was significantly increased in the ventral striatum among subjects with TS. Adults with TS+OCD exhibited a significant D(2)-R increase in left ventral striatum. SERT BP in midbrain and caudate/putamen was significantly increased in adults with TS (TS+OCD and TS-OCD). In three subjects with TS+OCD, in whom D2-R, 5-HT2AR, and SERT were measured within a 12-month period, there was a weakly significant elevation of DA rel and 5-HT2A BP, when compared with TS-OCD subjects and normal controls. The current study confirms, with a larger sample size and higher resolution PET scanning, our earlier report that elevated DA rel is a primary defect in TS. The finding of decreased SERT BP, and the possible elevation in 5-HT2AR in individuals with TS who had increased DA rel, suggest a condition of increased phasic DA rel modulated by low 5-HT in concomitant OCD.",

author = "Wong, {Dean F} and Brasic, {James R} and Singer, {Harvey S} and Schretlen, {David J} and Hiroto Kuwabara and Yun Zhou and Ayon Nandi and Maris, {Marika A} and Mohab Alexander and Weiguo Ye and Olivier Rousset and Anil Kumar and Zsolt Szabo and Albert Gjedde and Grace, {Anthony A}",

note = "Keywords: Adult; Amphetamine; Brain Mapping; Dopamine; Dopamine Agents; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Magnetic Resonance Imaging; Male; Models, Theoretical; Neuropsychological Tests; Obsessive-Compulsive Disorder; Positron-Emission Tomography; Psychiatric Status Rating Scales; Raclopride; Receptors, Dopamine D2; Serotonin; Synaptic Transmission; Tourette Syndrome",

year = "2007",

doi = "10.1038/sj.npp.1301528",

language = "English",

volume = "33",

pages = "1239--51",

journal = "Neuropsychopharmacology",

issn = "0893-133X",

publisher = "nature publishing group",

number = "6",

}

TY - JOUR

T1 - Mechanisms of dopaminergic and serotonergic neurotransmission in Tourette syndrome: clues from an in vivo neurochemistry study with PET

AU - Wong, Dean F

AU - Brasic, James R

AU - Singer, Harvey S

AU - Schretlen, David J

AU - Kuwabara, Hiroto

AU - Zhou, Yun

AU - Nandi, Ayon

AU - Maris, Marika A

AU - Alexander, Mohab

AU - Ye, Weiguo

AU - Rousset, Olivier

AU - Kumar, Anil

AU - Szabo, Zsolt

AU - Gjedde, Albert

AU - Grace, Anthony A

N1 - Keywords: Adult; Amphetamine; Brain Mapping; Dopamine; Dopamine Agents; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Magnetic Resonance Imaging; Male; Models, Theoretical; Neuropsychological Tests; Obsessive-Compulsive Disorder; Positron-Emission Tomography; Psychiatric Status Rating Scales; Raclopride; Receptors, Dopamine D2; Serotonin; Synaptic Transmission; Tourette Syndrome

PY - 2007

Y1 - 2007

N2 - Tourette syndrome (TS) is a neuropsychiatric disorder with childhood onset characterized by motor and phonic tics. Obsessive-compulsive disorder (OCD) is often concomitant with TS. Dysfunctional tonic and phasic dopamine (DA) and serotonin (5-HT) metabolism may play a role in the pathophysiology of TS. We simultaneously measured the density, affinity, and brain distribution of dopamine D2 receptors (D2-R's), dopamine transporter binding potential (BP), and amphetamine-induced dopamine release (DA(rel)) in 14 adults with TS and 10 normal adult controls. We also measured the brain distribution and BP of serotonin 5-HT2A receptors (5-HT2AR), and serotonin transporter (SERT) BP, in 11 subjects with TS and 10 normal control subjects. As compared with controls, DA rel was significantly increased in the ventral striatum among subjects with TS. Adults with TS+OCD exhibited a significant D(2)-R increase in left ventral striatum. SERT BP in midbrain and caudate/putamen was significantly increased in adults with TS (TS+OCD and TS-OCD). In three subjects with TS+OCD, in whom D2-R, 5-HT2AR, and SERT were measured within a 12-month period, there was a weakly significant elevation of DA rel and 5-HT2A BP, when compared with TS-OCD subjects and normal controls. The current study confirms, with a larger sample size and higher resolution PET scanning, our earlier report that elevated DA rel is a primary defect in TS. The finding of decreased SERT BP, and the possible elevation in 5-HT2AR in individuals with TS who had increased DA rel, suggest a condition of increased phasic DA rel modulated by low 5-HT in concomitant OCD.

AB - Tourette syndrome (TS) is a neuropsychiatric disorder with childhood onset characterized by motor and phonic tics. Obsessive-compulsive disorder (OCD) is often concomitant with TS. Dysfunctional tonic and phasic dopamine (DA) and serotonin (5-HT) metabolism may play a role in the pathophysiology of TS. We simultaneously measured the density, affinity, and brain distribution of dopamine D2 receptors (D2-R's), dopamine transporter binding potential (BP), and amphetamine-induced dopamine release (DA(rel)) in 14 adults with TS and 10 normal adult controls. We also measured the brain distribution and BP of serotonin 5-HT2A receptors (5-HT2AR), and serotonin transporter (SERT) BP, in 11 subjects with TS and 10 normal control subjects. As compared with controls, DA rel was significantly increased in the ventral striatum among subjects with TS. Adults with TS+OCD exhibited a significant D(2)-R increase in left ventral striatum. SERT BP in midbrain and caudate/putamen was significantly increased in adults with TS (TS+OCD and TS-OCD). In three subjects with TS+OCD, in whom D2-R, 5-HT2AR, and SERT were measured within a 12-month period, there was a weakly significant elevation of DA rel and 5-HT2A BP, when compared with TS-OCD subjects and normal controls. The current study confirms, with a larger sample size and higher resolution PET scanning, our earlier report that elevated DA rel is a primary defect in TS. The finding of decreased SERT BP, and the possible elevation in 5-HT2AR in individuals with TS who had increased DA rel, suggest a condition of increased phasic DA rel modulated by low 5-HT in concomitant OCD.

U2 - 10.1038/sj.npp.1301528

DO - 10.1038/sj.npp.1301528

M3 - Journal article

C2 - 17987065

SN - 0893-133X

VL - 33

SP - 1239

EP - 1251

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

IS - 6

ER -