Genetic variation in HTR2A influences serotonin transporter binding potential as measured using PET and [11C]DASB

Gonzalo Laje, Dara M. Cannon, Andrew S. Allen, Jackie M. Klaver, Summer A. Peck, Xinmin Liu, Husseini K. Manji, Wayne C. Drevets, Francis J. McMahon

Research output: Contribution to journalArticle

Abstract

In a previous study we showed that genetic variation in HTR2A, which encodes the serotonin 2A receptor, influenced outcome of citalopram treatment in patients with major depressive disorder. Since chronic administration of citalopram, which selectively and potently inhibits the serotonin transporter (5-HTT), putatively enhances serotonergic transmission, it is conceivable that genetic variation within HTR2A also influences pretreatment 5-HTT function or serotonergic transmission. The present study used positron emission tomography (PET) and the selective 5-HTT ligand, [11C]DASB, to investigate whether the HTR2A marker alleles that predict treatment outcome also predict differences in 5-HTT binding. Brain levels of 5-HTT were assessed in vivo using PET measures of the non-displaceable component of the [11C]DASB binding potential (BPND). DNA from 43 patients and healthy volunteers, all unmedicated, was genotyped with 14 single nucleotide polymorphisms located within or around HTR2A. Allelic association with BPND was assessed in eight brain regions, with covariates to control for race and ethnicity. We detected allelic association between [11C]DASB BPND in thalamus and three markers in a region spanning the 3 untranslated region and second intron of HTR2A (rs7333412, p=0.000045; rs7997012, p=0.000086; rs977003, p=0.000069). The association signal at rs7333412 remained significant (p

Original languageEnglish (US)
Pages (from-to)715-724
Number of pages10
JournalInternational Journal of Neuropsychopharmacology
Volume13
Issue number6
DOIs
StatePublished - Jul 2010
Externally publishedYes

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Positron-Emission Tomography
Citalopram
Receptor, Serotonin, 5-HT2A
Major Depressive Disorder
Brain
3' Untranslated Regions
Thalamus
Introns
Single Nucleotide Polymorphism
Healthy Volunteers
Alleles
Ligands
DNA
3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile

Keywords

  • [C]DASB
  • genetic association
  • HTR2A
  • positron emission tomography
  • serotonin transporter

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Psychiatry and Mental health
  • Medicine(all)

Cite this

Genetic variation in HTR2A influences serotonin transporter binding potential as measured using PET and [11C]DASB. / Laje, Gonzalo; Cannon, Dara M.; Allen, Andrew S.; Klaver, Jackie M.; Peck, Summer A.; Liu, Xinmin; Manji, Husseini K.; Drevets, Wayne C.; McMahon, Francis J.

In: International Journal of Neuropsychopharmacology, Vol. 13, No. 6, 07.2010, p. 715-724.

Research output: Contribution to journalArticle

Laje, G, Cannon, DM, Allen, AS, Klaver, JM, Peck, SA, Liu, X, Manji, HK, Drevets, WC & McMahon, FJ 2010, 'Genetic variation in HTR2A influences serotonin transporter binding potential as measured using PET and [11C]DASB', International Journal of Neuropsychopharmacology, vol. 13, no. 6, pp. 715-724. https://doi.org/10.1017/S1461145709991027
Laje, Gonzalo ; Cannon, Dara M. ; Allen, Andrew S. ; Klaver, Jackie M. ; Peck, Summer A. ; Liu, Xinmin ; Manji, Husseini K. ; Drevets, Wayne C. ; McMahon, Francis J. / Genetic variation in HTR2A influences serotonin transporter binding potential as measured using PET and [11C]DASB. In: International Journal of Neuropsychopharmacology. 2010 ; Vol. 13, No. 6. pp. 715-724.
@article{c2c8bbfe8fd84249b9100f5acd7a3d10,
title = "Genetic variation in HTR2A influences serotonin transporter binding potential as measured using PET and [11C]DASB",
abstract = "In a previous study we showed that genetic variation in HTR2A, which encodes the serotonin 2A receptor, influenced outcome of citalopram treatment in patients with major depressive disorder. Since chronic administration of citalopram, which selectively and potently inhibits the serotonin transporter (5-HTT), putatively enhances serotonergic transmission, it is conceivable that genetic variation within HTR2A also influences pretreatment 5-HTT function or serotonergic transmission. The present study used positron emission tomography (PET) and the selective 5-HTT ligand, [11C]DASB, to investigate whether the HTR2A marker alleles that predict treatment outcome also predict differences in 5-HTT binding. Brain levels of 5-HTT were assessed in vivo using PET measures of the non-displaceable component of the [11C]DASB binding potential (BPND). DNA from 43 patients and healthy volunteers, all unmedicated, was genotyped with 14 single nucleotide polymorphisms located within or around HTR2A. Allelic association with BPND was assessed in eight brain regions, with covariates to control for race and ethnicity. We detected allelic association between [11C]DASB BPND in thalamus and three markers in a region spanning the 3 untranslated region and second intron of HTR2A (rs7333412, p=0.000045; rs7997012, p=0.000086; rs977003, p=0.000069). The association signal at rs7333412 remained significant (p",
keywords = "[C]DASB, genetic association, HTR2A, positron emission tomography, serotonin transporter",
author = "Gonzalo Laje and Cannon, {Dara M.} and Allen, {Andrew S.} and Klaver, {Jackie M.} and Peck, {Summer A.} and Xinmin Liu and Manji, {Husseini K.} and Drevets, {Wayne C.} and McMahon, {Francis J.}",
year = "2010",
month = "7",
doi = "10.1017/S1461145709991027",
language = "English (US)",
volume = "13",
pages = "715--724",
journal = "International Journal of Neuropsychopharmacology",
issn = "1461-1457",
publisher = "Cambridge University Press",
number = "6",

}

TY - JOUR

T1 - Genetic variation in HTR2A influences serotonin transporter binding potential as measured using PET and [11C]DASB

AU - Laje, Gonzalo

AU - Cannon, Dara M.

AU - Allen, Andrew S.

AU - Klaver, Jackie M.

AU - Peck, Summer A.

AU - Liu, Xinmin

AU - Manji, Husseini K.

AU - Drevets, Wayne C.

AU - McMahon, Francis J.

PY - 2010/7

Y1 - 2010/7

N2 - In a previous study we showed that genetic variation in HTR2A, which encodes the serotonin 2A receptor, influenced outcome of citalopram treatment in patients with major depressive disorder. Since chronic administration of citalopram, which selectively and potently inhibits the serotonin transporter (5-HTT), putatively enhances serotonergic transmission, it is conceivable that genetic variation within HTR2A also influences pretreatment 5-HTT function or serotonergic transmission. The present study used positron emission tomography (PET) and the selective 5-HTT ligand, [11C]DASB, to investigate whether the HTR2A marker alleles that predict treatment outcome also predict differences in 5-HTT binding. Brain levels of 5-HTT were assessed in vivo using PET measures of the non-displaceable component of the [11C]DASB binding potential (BPND). DNA from 43 patients and healthy volunteers, all unmedicated, was genotyped with 14 single nucleotide polymorphisms located within or around HTR2A. Allelic association with BPND was assessed in eight brain regions, with covariates to control for race and ethnicity. We detected allelic association between [11C]DASB BPND in thalamus and three markers in a region spanning the 3 untranslated region and second intron of HTR2A (rs7333412, p=0.000045; rs7997012, p=0.000086; rs977003, p=0.000069). The association signal at rs7333412 remained significant (p

AB - In a previous study we showed that genetic variation in HTR2A, which encodes the serotonin 2A receptor, influenced outcome of citalopram treatment in patients with major depressive disorder. Since chronic administration of citalopram, which selectively and potently inhibits the serotonin transporter (5-HTT), putatively enhances serotonergic transmission, it is conceivable that genetic variation within HTR2A also influences pretreatment 5-HTT function or serotonergic transmission. The present study used positron emission tomography (PET) and the selective 5-HTT ligand, [11C]DASB, to investigate whether the HTR2A marker alleles that predict treatment outcome also predict differences in 5-HTT binding. Brain levels of 5-HTT were assessed in vivo using PET measures of the non-displaceable component of the [11C]DASB binding potential (BPND). DNA from 43 patients and healthy volunteers, all unmedicated, was genotyped with 14 single nucleotide polymorphisms located within or around HTR2A. Allelic association with BPND was assessed in eight brain regions, with covariates to control for race and ethnicity. We detected allelic association between [11C]DASB BPND in thalamus and three markers in a region spanning the 3 untranslated region and second intron of HTR2A (rs7333412, p=0.000045; rs7997012, p=0.000086; rs977003, p=0.000069). The association signal at rs7333412 remained significant (p

KW - [C]DASB

KW - genetic association

KW - HTR2A

KW - positron emission tomography

KW - serotonin transporter

UR - http://www.scopus.com/inward/record.url?scp=77957130434&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957130434&partnerID=8YFLogxK

U2 - 10.1017/S1461145709991027

DO - 10.1017/S1461145709991027

M3 - Article

C2 - 20047709

AN - SCOPUS:77957130434

VL - 13

SP - 715

EP - 724

JO - International Journal of Neuropsychopharmacology

JF - International Journal of Neuropsychopharmacology

SN - 1461-1457

IS - 6

ER -