Skip to main content

Advertisement

SpringerLink
Log in

Family-based association study of serotonergic candidate genes and attention-deficit/hyperactivity disorder in a German sample

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

Alterations in the serotonergic pathway have been implicated in the pathogenesis of attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to investigate seven genetic variants in three genes (serotonin transporter (5-HTT), serotonin receptor 1B (5-HTR1B) and serotonin receptor 2A (5-HTR2A)), which have previously been shown to be associated with ADHD. The polymorphisms under investigation were the 5-HTTLPR, the VNTR in intron 2 and the 3′UTR SNP in 5-HTT, the 5-HTR1B variations 861G>C and 102T>C, and the 5-HTR2A variations His452Tyr and 1438G>A. We genotyped these variants in a sample of 102 families with 229 children with ADHD according to DSM-IV criteria. Among the affected children, 69% fulfilled criteria for the combined type, 27% for the predominantly inattentive type, and 4% for the predominantly hyperactive-impulsive type. Associations were tested by the pedigree transmission disequilibrium test (PDT). All investigated polymorphisms in serotonergic candidate genes showed no association to ADHD in our sample. Earlier studies of these polymorphisms had also shown inconsistent results, with some studies reporting significant associations and others demonstrating no association. This discordance between studies may reflect variation in patient ascertainment criteria, genetic heterogeneity, too low statistical power for the expected effects or false positive results in the initial reports. We cannot rule out the possibility that other variations in the investigated genes contribute to the etiology of ADHD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

5-HTT:

5-hydroxytryptamine (=serotonin) transporter

5-HTR:

serotonin receptor

aa:

amino acid

ADHD:

attention-deficit/hyperactivity disorder

bp:

base pair

c–c:

case control

CD:

conduct disorder

chr:

chromosome

COMT:

catechol-O-methyltransferase

DAT1:

dopamine transporter 1 (solute carrier family 6, member 3 (SLC6A3))

DBH:

dopamine β-hydroxylase

DRD:

dopamine receptor

DSM-IV:

Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition

duo:

one affected child and one parent (mostly mother)

EDTD:

extended transmission disequilibrium test

Fam:

family-based association study

HHRR:

haplotype-based haplotype relative risk

HRR:

haplotype relative risk

LOD:

logarithm of the odds

MAOA:

monoamine oxidase A

MAOB:

monoamine oxidase B

MPH:

methlyphenidate

n.a.:

not applicable

n.s.:

not significant

ODD:

oppositional defiant disorder

quartett:

two affected children and both parents

quintett:

three affected children and both parents

SNPs:

single nucleotide polymorphisms

TDT:

transmission disequilibrium test

TPH:

tryptophan hydroxylase

trio:

one affected child and both parents

VNTR:

variable number tandem repeat

References

  • MJ Arranz DA Collier J Munro P Sham G Kirov M Sodhi G Roberts J Price RW Kerwin (1996) ArticleTitleAnalysis of a structural polymorphism in the 5-HT2A receptor and clinical response to clozapine Neurosci Lett 217 177–178 Occurrence Handle8916101 Occurrence Handle10.1016/0304-3940(96)13094-9 Occurrence Handle1:CAS:528:DyaK28XmslGns74%3D

    Article  PubMed  CAS  Google Scholar 

  • E Banerjee S Sinha A Chatterjee PK Gangopadhyay M Singh K Nandagopal (2006) ArticleTitleA family-based study of Indian subjects from Kolkata reveals allelic association of the serotonin transporter intron-2 (STin2) polymorphism and attention-deficit-hyperactivity disorder (ADHD) Am J Med Genet B Neuropsychiatr Genet 141 361–366 Occurrence Handle16583436

    PubMed  Google Scholar 

  • NM Barnes T Sharp (1999) ArticleTitleA review of central 5-HT receptors and their function Neuropharmacology 38 1083–1152 Occurrence Handle10462127 Occurrence Handle10.1016/S0028-3908(99)00010-6 Occurrence Handle1:CAS:528:DyaK1MXltVCgsrg%3D

    Article  PubMed  CAS  Google Scholar 

  • S Battersby AD Ogilvie DH Blackwood S Shen MM Muqit WJ Muir P Teague GM Goodwin AJ Harmar (1999) ArticleTitlePresence of multiple functional polyadenylation signals and a single nucleotide polymorphism in the 3′ untranslated region of the human serotonin transporter gene J Neurochem 72 1384–1388 Occurrence Handle10098839 Occurrence Handle10.1046/j.1471-4159.1999.721384.x Occurrence Handle1:CAS:528:DyaK1MXitFCksrg%3D

    Article  PubMed  CAS  Google Scholar 

  • JH Beitchman KM Davidge JL Kennedy L Atkinson V Lee S Shapiro L Douglas (2003) ArticleTitleThe serotonin transporter gene in aggressive children with and without ADHD and nonaggressive matched controls Ann NY Acad Sci 1008 248–251 Occurrence Handle14998889 Occurrence Handle10.1196/annals.1301.025 Occurrence Handle1:CAS:528:DC%2BD2cXisFCjur8%3D

    Article  PubMed  CAS  Google Scholar 

  • D Bengel DL Murphy AM Andrews CH Wichems D Feltner A Heils R Mossner H Westphal KP Lesch (1998) ArticleTitleAltered brain serotonin homeostasis and locomotor insensitivity to 3,4-methylenedioxymethamphetamine (“Ecstasy”) in serotonin transporter-deficient mice Mol Pharmacol 53 649–655 Occurrence Handle9547354 Occurrence Handle1:CAS:528:DyaK1cXislCgtL0%3D

    PubMed  CAS  Google Scholar 

  • AJ Bobb AM Addington E Sidransky MC Gornick JP Lerch DK Greenstein LS Clasen WS Sharp G Inoff-Germain F Wavrant-De Vrieze M Arcos-Burgos RE Straub JA Hardy FX Castellanos JL Rapoport (2005) ArticleTitleSupport for association between ADHD and two candidate genes: NET1 and DRD1 Am J Med Genet B Neuropsychiatr Genet 134 67–72 Occurrence Handle15717291

    PubMed  Google Scholar 

  • N Bonhomme P De Deurwaerdere M Le Moal U Spampinato (1995) ArticleTitleEvidence for 5-HT4 receptor subtype involvement in the enhancement of striatal dopamine release induced by serotonin: a microdialysis study in the halothane-anesthetized rat Neuropharmacology 34 269–279 Occurrence Handle7543190 Occurrence Handle10.1016/0028-3908(94)00145-I Occurrence Handle1:CAS:528:DyaK2MXlsFKrtb0%3D

    Article  PubMed  CAS  Google Scholar 

  • D Brunner R Hen (1997) ArticleTitleInsights into the neurobiology of impulsive behavior from serotonin receptor knockout mice Ann NY Acad Sci 836 81–105 Occurrence Handle9616795 Occurrence Handle10.1111/j.1749-6632.1997.tb52356.x Occurrence Handle1:CAS:528:DyaK1cXmsFahug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • H Campbell I Rudan (2002) ArticleTitleInterpretation of genetic association studies in complex disease Pharmacogenomics J 2 349–360 Occurrence Handle12629506 Occurrence Handle10.1038/sj.tpj.6500132 Occurrence Handle1:CAS:528:DC%2BD3sXisVarsLw%3D

    Article  PubMed  CAS  Google Scholar 

  • S Curran S Purcell I Craig P Asherson P Sham (2005) ArticleTitleThe serotonin transporter gene as a QTL for ADHD Am J Med Genet B Neuropsychiatr Genet 134 42–47 Occurrence Handle15719397

    PubMed  Google Scholar 

  • K Domschke K Sheehan N Lowe A Kirley C Mullins R O’sullivan C Freitag T Becker J Conroy M Fitzgerald M Gill Z Hawi (2005) ArticleTitleAssociation analysis of the monoamine oxidase A and B genes with attention deficit hyperactivity disorder (ADHD) in an Irish sample: preferential transmission of the MAO-A 941G allele to affected children Am J Med Genet B Neuropsychiatr Genet 134 110–114 Occurrence Handle15717295

    PubMed  Google Scholar 

  • J Erdmann D Shimron-Abarbanell M Rietschel M Albus W Maier J Korner B Bondy K Chen JC Shih M Knapp P Propping MM Nothen (1996) ArticleTitleSystematic screening for mutations in the human serotonin-2A (5-HT2A) receptor gene: identification of two naturally occurring receptor variants and association analysis in schizophrenia Hum Genet 97 614–619 Occurrence Handle8655141 Occurrence Handle1:CAS:528:DyaK28XivFaitL0%3D

    PubMed  CAS  Google Scholar 

  • SV Faraone RH Perlis AE Doyle JW Smoller JJ Goralnick MA Holmgren P Sklar (2005) ArticleTitleMolecular genetics of attention-deficit/hyperactivity disorder Biol Psychiatry 57 1313–1323 Occurrence Handle15950004 Occurrence Handle10.1016/j.biopsych.2004.11.024 Occurrence Handle1:CAS:528:DC%2BD2MXltFSrsrg%3D

    Article  PubMed  CAS  Google Scholar 

  • RR Gainetdinov WC Wetsel SR Jones ED Levin M Jaber MG Caron (1999) ArticleTitleRole of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity Science 283 397–401 Occurrence Handle9888856 Occurrence Handle10.1126/science.283.5400.397 Occurrence Handle1:CAS:528:DyaK1MXns1CitQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • WJ Gauderman (2002) ArticleTitleSample size requirements for matched case-control studies of gene-environment interaction Stat Med 21 35–50 Occurrence Handle11782049 Occurrence Handle10.1002/sim.973

    Article  PubMed  Google Scholar 

  • B Giros M Jaber SR Jones RM Wightman MG Caron (1996) ArticleTitleHyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter Nature 379 606–612 Occurrence Handle8628395 Occurrence Handle10.1038/379606a0 Occurrence Handle1:CAS:528:DyaK28XhtFKrurg%3D

    Article  PubMed  CAS  Google Scholar 

  • JM Halperin JH Newcorn ST Schwartz V Sharma LJ Siever VH Koda S Gabriel (1997) ArticleTitleAge-related changes in the association between serotonergic function and aggression in boys with ADHD Biol Psychiatry 41 682–689 Occurrence Handle9066992 Occurrence Handle10.1016/S0006-3223(96)00168-0 Occurrence Handle1:CAS:528:DyaK2sXit12ksrg%3D

    Article  PubMed  CAS  Google Scholar 

  • Z Hawi M Dring A Kirley D Foley L Kent N Craddock P Asherson S Curran A Gould S Richards D Lawson H Pay D Turic K Langley M Owen M O’Donovan A Thapar M Fitzgerald M Gill (2002) ArticleTitleSerotonergic system and attention deficit hyperactivity disorder (ADHD): a potential susceptibility locus at the 5-HT(1B) receptor gene in 273 nuclear families from a multi-centre sample Mol Psychiatry 7 718–725 Occurrence Handle12192616 Occurrence Handle10.1038/sj.mp.4001048 Occurrence Handle1:CAS:528:DC%2BD38Xmt12qurY%3D

    Article  PubMed  CAS  Google Scholar 

  • J Hebebrand A Dempfle K Saar H Thiele B Herpertz-Dahlmann M Linder H Kiefl H Remschmidt U Hemminger A Warnke U Knolker P Heiser S Friedel A Hinney H Schafer P Nurnberg K Konrad (2006) ArticleTitleA genome-wide scan for attention-deficit/hyperactivity disorder in 155 german sib-pairs Mol Psychiatry 11 196–205 Occurrence Handle16222334 Occurrence Handle10.1038/sj.mp.4001761 Occurrence Handle1:CAS:528:DC%2BD28XnsV2mtw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • A Heils A Teufel S Petri G Stober P Riederer D Bengel KP Lesch (1996) ArticleTitleAllelic variation of human serotonin transporter gene expression J Neurochem 66 2621–2624 Occurrence Handle8632190 Occurrence Handle1:CAS:528:DyaK28XjtFCrsrk%3D Occurrence Handle10.1046/j.1471-4159.1996.66062621.x

    Article  PubMed  CAS  Google Scholar 

  • P Heiser S Friedel A Dempfle K Konrad J Smidt J Grabarkiewicz B Herpertz-Dahlmann H Remschmidt J Hebebrand (2004) ArticleTitleMolecular genetic aspects of attention-deficit/hyperactivity disorder Neurosci Biobehav Rev 28 625–641 Occurrence Handle15527867 Occurrence Handle10.1016/j.neubiorev.2004.09.010 Occurrence Handle1:CAS:528:DC%2BD2cXpsVOmu7g%3D

    Article  PubMed  CAS  Google Scholar 

  • A Hinney N Barth A Ziegler S von Prittwitz A Hamann K Hennighausen KM Pirke A Heils K Rosenkranz H Roth H Coners H Mayer W Herzog A Siegfried G Lehmkuhl F Poustka MH Schmidt H Schafer KH Grzeschik KP Lesch KU Lentes H Remschmidt J Hebebrand (1997) ArticleTitleSerotonin transporter gene-linked polymorphic region: allele distributions in relationship to body weight and in anorexia nervosa Life Sci 61 295–303 Occurrence Handle10.1016/S0024-3205(97)00888-6

    Article  Google Scholar 

  • A Holmes DL Murphy JN Crawley (2002) ArticleTitleReduced aggression in mice lacking the serotonin transporter Psychopharmacology (Berl) 161 160–167 Occurrence Handle10.1007/s00213-002-1024-3 Occurrence Handle1:CAS:528:DC%2BD38Xlt1egtrg%3D

    Article  CAS  Google Scholar 

  • S Jiang R Xin X Wu S Lin Y Qian D Ren G Tang D Wang (2000) ArticleTitleAssociation between attention deficit hyperactivity disorder and the DXS7 locus Am J Med Genet 96 289–292 Occurrence Handle10898902 Occurrence Handle10.1002/1096-8628(20000612)96:3<289::AID-AJMG11>3.0.CO;2-Z Occurrence Handle1:STN:280:DC%2BD3czptVWrtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • S Jiang R Xin S Lin Y Qian G Tang D Wang X Wu (2001) ArticleTitleLinkage studies between attention-deficit hyperactivity disorder and the monoamine oxidase genes Am J Med Genet 105 783–788 Occurrence Handle11803531 Occurrence Handle10.1002/ajmg.10098 Occurrence Handle1:STN:280:DC%2BD38%2FnsVOiug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • M Johann G Bobbe A Putzhammer N Wodarz (2003) ArticleTitleComorbidity of alcohol dependence with attention-deficit hyperactivity disorder: differences in phenotype with increased severity of the substance disorder, but not in genotype (serotonin transporter and 5-hydroxytryptamine-2c receptor) Alcohol Clin Exp Res 27 1527–1534 Occurrence Handle14574222 Occurrence Handle10.1097/01.ALC.0000090143.00703.07 Occurrence Handle1:CAS:528:DC%2BD3sXotlWqtLc%3D

    Article  PubMed  CAS  Google Scholar 

  • L Kent U Doerry E Hardy R Parmar K Gingell Z Hawi A Kirley N Lowe M Fitzgerald M Gill N Craddock (2002) ArticleTitleEvidence that variation at the serotonin transporter gene influences susceptibility to attention deficit hyperactivity disorder (ADHD): analysis and pooled analysis Mol Psychiatry 7 908–912 Occurrence Handle12232786 Occurrence Handle10.1038/sj.mp.4001100 Occurrence Handle1:CAS:528:DC%2BD38XntVaitbs%3D

    Article  PubMed  CAS  Google Scholar 

  • SJ Kim J Badner KA Cheon BN Kim HJ Yoo SJ Kim E Cook SuffixJr BL Leventhal YS Kim (2005) ArticleTitleFamily-based association study of the serotonin transporter gene polymorphisms in Korean ADHD trios Am J Med Genet B Neuropsychiatr Genet 139 14–18 Occurrence Handle16082698

    PubMed  Google Scholar 

  • NM Laird C Lange (2006) ArticleTitleFamily-based designs in the age of large-scale gene-association studies Nat Rev Genet 7 385–394 Occurrence Handle16619052 Occurrence Handle10.1038/nrg1839 Occurrence Handle1:CAS:528:DC%2BD28XjsFSqt7g%3D

    Article  PubMed  CAS  Google Scholar 

  • Lange C, van Stehen K, Andrew T, Lyon H, DeMeo DL, Raby B, Murphy A, Silverman EK, MacGregor A, Weiss ST, Laird NM (2004) A family-based association test for repeatedly measured quantitative traits adjusting for unknown environmental and/or polygenic effects. Stat Appl Genet Mol Biol 3: Article 17

  • K Langley A Payton ML Hamshere HM Pay DC Lawson D Turic W Ollier J Worthington MJ Owen MC O’Donovan A Thapar (2003) ArticleTitleNo evidence of association of two 5HT transporter gene polymorphisms and attention deficit hyperactivity disorder Psychiatr Genet 13 107–110 Occurrence Handle12782968 Occurrence Handle10.1097/00041444-200306000-00009

    Article  PubMed  Google Scholar 

  • DC Lawson D Turic K Langley HM Pay CF Govan N Norton ML Hamshere MJ Owen MC O’Donovan A Thapar (2003) ArticleTitleAssociation analysis of monoamine oxidase A and attention deficit hyperactivity disorder Am J Med Genet B Neuropsychiatr Genet 116 84–89 Occurrence Handle12497620 Occurrence Handle10.1002/ajmg.b.10002

    Article  PubMed  Google Scholar 

  • KP Lesch U Balling J Gross K Strauss BL Wolozin DL Murphy P Riederer (1994) ArticleTitleOrganization of the human serotonin transporter gene J Neural Transm Gen Sect 95 157–162 Occurrence Handle7865169 Occurrence Handle10.1007/BF01276434 Occurrence Handle1:CAS:528:DyaK2MXhsVWnsw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • KP Lesch D Bengel A Heils SZ Sabol BD Greenberg S Petri J Benjamin CR Muller DH Hamer DL Murphy (1996) ArticleTitleAssociation of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region Science 274 1527–1531 Occurrence Handle8929413 Occurrence Handle10.1126/science.274.5292.1527 Occurrence Handle1:CAS:528:DyaK28Xnt1ansL8%3D

    Article  PubMed  CAS  Google Scholar 

  • RD Levitan M Masellis VS Basile RW Lam U Jain AS Kaplan SH Kennedy G Siegel ML Walker FJ Vaccarino JL Kennedy (2002) ArticleTitlePolymorphism of the serotonin-2A receptor gene (HTR2A) associated with childhood attention deficit hyperactivity disorder (ADHD) in adult women with seasonal affective disorder J Affect Disord 71 229–233 Occurrence Handle12167522 Occurrence Handle10.1016/S0165-0327(01)00372-X Occurrence Handle1:CAS:528:DC%2BD38XmtVWmsLk%3D

    Article  PubMed  CAS  Google Scholar 

  • J Li Y Wang Q Qian B Wang R Zhou (2002) ArticleTitleAssociation of 5-HT(2A) receptor polymorphism and attention deficit hyperactivity disorder in children Zhonghua Yi Xue Za Zhi 82 1173–1176 Occurrence Handle12475403 Occurrence Handle1:CAS:528:DC%2BD3sXhvVylsb4%3D

    PubMed  CAS  Google Scholar 

  • J Li YF Wang RL Zhou HB Zhang B Wang L Yang (2004) ArticleTitleAssociation between serotonin 2C gene polymorphisms and attention deficit hyperactivity disorder comorbid or not comorbid with learning disorder Beijing Da Xue Xue Bao 36 366–369 Occurrence Handle15303127 Occurrence Handle1:CAS:528:DC%2BD2cXhtVylsLjI

    PubMed  CAS  Google Scholar 

  • J Li Y Wang R Zhou H Zhang L Yang B Wang S Khan SV Faraone (2005) ArticleTitleSerotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder in Chinese Han subjects Am J Med Genet B Neuropsychiatr Genet 132B 59–63 Occurrence Handle10.1002/ajmg.b.30075 Occurrence Handle15578608

    Article  PubMed  Google Scholar 

  • Li J, Wang Y, Zhou R, Zhang H, Yang L, Wang B, Faraone SV (2006a) Association between polymorphisms in serotonin transporter gene and attention deficit hyperactivity disorder in Chinese Han subjects. Am J Med Genet B Neuropsychiatr Genet 2006 Aug 29 [Epub ahead of print]

  • Li J, Wang Y, Zhou R, Wang B, Zhang H, Yang L, Faraone SV (2006b) No association of attention-deficit/hyperactivity disorder with genes of the serotonergic pathway in Han Chinese subjects. Neurosci Lett 2006 Jul 31; 403: 172–175

    Google Scholar 

  • J Li C Kang Y Wang R Zhou B Wang L Guan L Yang SV Faraone (2006c) ArticleTitleContribution of 5-HT2A receptor gene – 1438A>G polymorphism to outcome of attention-deficit/hyperactivity disorder in adolescents Am J Med Genet B Neuropsychiatr Genet 141 473–476

    Google Scholar 

  • J Li Y Wang R Zhou B Wang H Zhang L Yang SV Faraone (2006d) ArticleTitleAssociation of attention-deficit/hyperactivity disorder with serotonin 4 receptor gene polymorphisms in Han Chinese subjects Neurosci Lett 401 6–9 Occurrence Handle10.1016/j.neulet.2006.02.053 Occurrence Handle1:CAS:528:DC%2BD28Xks1Olurw%3D

    Article  CAS  Google Scholar 

  • A MacKenzie J Quinn (1999) ArticleTitleA serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo Proc Natl Acad Sci USA 96 15251–15255 Occurrence Handle10611371 Occurrence Handle10.1073/pnas.96.26.15251 Occurrence Handle1:CAS:528:DC%2BD3cXhtFeisw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • I Manor J Eisenberg S Tyano Y Sever H Cohen RP Ebstein M Kotler (2001) ArticleTitleFamily-based association study of the serotonin transporter promoter region polymorphism (5-HTTLPR) in attention deficit hyperactivity disorder Am J Med Genet 105 91–95 Occurrence Handle11425009 Occurrence Handle10.1002/1096-8628(20010108)105:1<91::AID-AJMG1069>3.0.CO;2-V Occurrence Handle1:STN:280:DC%2BD3Mzmtlenug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • I Manor S Tyano E Mel J Eisenberg R Bachner-Melman M Kotler RP Ebstein (2002) ArticleTitleFamily-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD): preferential transmission of the long promoter-region repeat and its association with impaired performance on a continuous performance test (TOVA) Mol Psychiatry 7 626–632 Occurrence Handle12140786 Occurrence Handle10.1038/sj.mp.4001037 Occurrence Handle1:CAS:528:DC%2BD38XlsFWrsbs%3D

    Article  PubMed  CAS  Google Scholar 

  • ER Martin SA Monks LL Warren NL Kaplan (2000) ArticleTitleA test for linkage and association in general pedigrees: the pedigree disequilibrium test Am J Hum Genet 67 146–154 Occurrence Handle10825280 Occurrence Handle10.1086/302957 Occurrence Handle1:STN:280:DC%2BD3czptVWntQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • J Mill X Xu A Ronald S Curran T Price J Knight I Craig P Sham R Plomin P Asherson (2005) ArticleTitleQuantitative trait locus analysis of candidate gene alleles associated with attention deficit hyperactivity disorder (ADHD) in five genes: DRD4, DAT1, DRD5, SNAP-25, and 5HT1B Am J Med Genet B Neuropsychiatr Genet 133 68–73 Occurrence Handle15578613

    PubMed  Google Scholar 

  • JR O’Connell DE Weeks (1998) ArticleTitlePedCheck: a program for identification of genotype incompatibilities in linkage analysis Am J Hum Genet 63 259–266 Occurrence Handle9634505 Occurrence Handle10.1086/301904 Occurrence Handle1:STN:280:DyaK1c3pvFyhsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • MF O’Neill CL Heron-Maxwell G Shaw (1999) ArticleTitle5-HT2 receptor antagonism reduces hyperactivity induced by amphetamine, cocaine, and MK-801 but not D1 agonist C-APB Pharmacol Biochem Behav 63 237–243 Occurrence Handle10371652 Occurrence Handle10.1016/S0091-3057(98)00240-8 Occurrence Handle1:CAS:528:DyaK1MXjsVylurY%3D

    Article  PubMed  CAS  Google Scholar 

  • A Payton J Holmes JH Barrett T Hever H Fitzpatrick AL Trumper R Harrington P McGuffin M O’Donovan M Owen W Ollier J Worthington A Thapar (2001) ArticleTitleExamining for association between candidate gene polymorphisms in the dopamine pathway and attention-deficit hyperactivity disorder: a family-based study Am J Med Genet 105 464–470 Occurrence Handle11449400 Occurrence Handle10.1002/ajmg.1407 Occurrence Handle1:STN:280:DC%2BD3MzpslShug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • JF Quist CL Barr R Schachar W Roberts M Malone R Tannock VS Basile J Beitchman JL Kennedy (2000) ArticleTitleEvidence for the serotonin HTR2A receptor gene as a susceptibility factor in attention deficit hyperactivity disorder (ADHS) Mol Psychiatry 5 537–541 Occurrence Handle11032388 Occurrence Handle10.1038/sj.mp.4000779 Occurrence Handle1:CAS:528:DC%2BD3cXntVCgt74%3D

    Article  PubMed  CAS  Google Scholar 

  • JF Quist CL Barr R Schachar W Roberts M Malone R Tannock VS Basile J Beitchman JL Kennedy (2003) ArticleTitleThe serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder Mol Psychiatry 8 98–102 Occurrence Handle12556913 Occurrence Handle10.1038/sj.mp.4001244 Occurrence Handle1:CAS:528:DC%2BD3sXntl2lsQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • H Remschmidt InstitutionalAuthorNameGlobal ADHD Working Group (2005) ArticleTitleGlobal consensus on ADHD/HKD Eur Child Adolesc Psychiatry 14 127–137 Occurrence Handle15959658 Occurrence Handle10.1007/s00787-005-0439-x

    Article  PubMed  Google Scholar 

  • W Retz J Thome D Blocher M Baader M Rosler (2002) ArticleTitleAssociation of attention deficit hyperactivity disorder-related psychopathology and personality traits with the serotonin transporter promoter region polymorphism Neurosci Lett 319 133–136 Occurrence Handle11834311 Occurrence Handle10.1016/S0304-3940(01)02575-7 Occurrence Handle1:CAS:528:DC%2BD38XhtVKlt7w%3D

    Article  PubMed  CAS  Google Scholar 

  • W Retz P Retz-Junginger T Supprian J Thome M Rosler (2004) ArticleTitleAssociation of serotonin transporter promoter gene polymorphism with violence: relation with personality disorders, impulsivity, and childhood ADHD psychopathology Behav Sci Law 22 415–425 Occurrence Handle15211560 Occurrence Handle10.1002/bsl.589

    Article  PubMed  Google Scholar 

  • F Saudou DA Amara A Dierich M LeMeur S Ramboz L Segu MC Buhot R Hen (1994) ArticleTitleEnhanced aggressive behavior in mice lacking 5-HT1B receptor Science 265 1875–1878 Occurrence Handle8091214 Occurrence Handle10.1126/science.8091214 Occurrence Handle1:CAS:528:DyaK2cXlvFKlt7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • KP Schulz JH Newcorn KE McKay J Himelstein VH Koda LJ Siever V Sharma JM Halperin (2001) ArticleTitleRelationship between central serotonergic function and aggression in prepubertal boys: effect of age and attention-deficit/hyperactivity disorder Psychiatry Res 101 1–10 Occurrence Handle11223114 Occurrence Handle10.1016/S0165-1781(00)00238-9 Occurrence Handle1:CAS:528:DC%2BD3MXht1Orurk%3D

    Article  PubMed  CAS  Google Scholar 

  • G Seeger P Schloss MH Schmidt (2001) ArticleTitleFunctional polymorphism within the promotor of the serotonin transporter gene is associated with severe hyperkinetic disorders Mol Psychiatry 6 235–238 Occurrence Handle11317229 Occurrence Handle10.1038/sj.mp.4000820 Occurrence Handle1:CAS:528:DC%2BD3MXhsFGlu7g%3D

    Article  PubMed  CAS  Google Scholar 

  • K Sheehan N Lowe A Kirley C Mullins M Fitzgerald M Gill Z Hawi (2005) ArticleTitleTryptophan hydroxylase 2 (TPH2) gene variants associated with ADHD Mol Psychiatry 10 944–949 Occurrence Handle15940290 Occurrence Handle10.1038/sj.mp.4001698 Occurrence Handle1:CAS:528:DC%2BD2MXhtVelsbnJ

    Article  PubMed  CAS  Google Scholar 

  • RS Spielman RE McGinnis WJ Ewens (1993) ArticleTitleTransmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM) Am J Hum Genet 52 506–516 Occurrence Handle8447318 Occurrence Handle1:STN:280:DyaK3s7ptV2rsA%3D%3D

    PubMed  CAS  Google Scholar 

  • A Thapar M O’donovan MJ Owen (2005) ArticleTitleThe genetics of attention deficit hyperactivity disorder Hum Mol Genet 14 IssueIDSuppl 2 R275–R282 Occurrence Handle16244326 Occurrence Handle10.1093/hmg/ddi263 Occurrence Handle1:CAS:528:DC%2BD2MXhtFCjtLzF

    Article  PubMed  CAS  Google Scholar 

  • S Walitza TJ Renner A Dempfle K Konrad C Wewetzer A Halbach B Herpertz-Dahlmann H Remschmidt J Smidt M Linder L Flierl U Knolker S Friedel H Schafer C Gross J Hebebrand A Warnke KP Lesch (2005) ArticleTitleTransmission disequilibrium of polymorphic variants in the tryptophan hydroxylase-2 gene in attention-deficit/hyperactivity disorder Mol Psychiatry 10 1126–1132 Occurrence Handle16116490 Occurrence Handle10.1038/sj.mp.4001734 Occurrence Handle1:CAS:528:DC%2BD2MXht1Ghu7zJ

    Article  PubMed  CAS  Google Scholar 

  • DJ Walther JU Peter S Bashammakh H Hortnagl M Voits H Fink M Bader (2003) ArticleTitleSynthesis of serotonin by a second tryptophan hydroxylase isoform Science 299 76 Occurrence Handle12511643 Occurrence Handle10.1126/science.1078197 Occurrence Handle1:CAS:528:DC%2BD3sXptVWqug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • HJ Wang F Geller A Dempfle N Schauble S Friedel P Lichtner F Fontenla-Horro S Wudy S Hagemann L Gortner K Huse H Remschmidt T Bettecken T Meitinger H Schafer J Hebebrand A Hinney (2004) ArticleTitleGhrelin receptor gene: identification of several sequence variants in extremely obese children and adolescents, healthy normal-weight and underweight students, and children with short normal stature J Clin Endocrinol Metab 89 157–162 Occurrence Handle14715843 Occurrence Handle10.1210/jc.2003-031395 Occurrence Handle1:CAS:528:DC%2BD2cXmvFeqsw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • KG Wigg A Takhar A Ickowicz R Tannock JL Kennedy T Pathare M Malone R Schachar CL Barr (2006) ArticleTitleGene for the serotonin transporter and ADHD. No association with two functional polymorphisms Am J Med Genet B Neuropsychiatr Genet 141 566–570 Occurrence Handle16856124

    PubMed  Google Scholar 

  • X Xu J Mill CK Chen K Brookes E Taylor P Asherson (2005) ArticleTitleFamily-based association study of serotonin transporter gene polymorphisms in attention deficit hyperactivity disorder: No evidence for association in UK and Taiwanese samples Am J Med Genet B Neuropsychiatr Genet 139 11–13 Occurrence Handle16082690

    PubMed  Google Scholar 

  • AL Zhao LY Su YH Zhang BS Tang XR Luo CX Huang QR Su (2005) ArticleTitleAssociation analysis of serotonin transporter promoter gene polymorphism with ADHD and related symptomatology Int J Neurosci 115 1183–1191 Occurrence Handle16040360 Occurrence Handle10.1080/00207450590914545 Occurrence Handle1:CAS:528:DC%2BD2MXntVGqs7k%3D

    Article  PubMed  CAS  Google Scholar 

  • KT Zondervan LR Cardon (2004) ArticleTitleThe complex interplay among factors that influence allelic association Nat Rev Genet 5 89–100 Occurrence Handle14735120 Occurrence Handle10.1038/nrg1270 Occurrence Handle1:CAS:528:DC%2BD2cXovV2msw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • SS Zoroglu ME Erdal B Alasehirli N Erdal E Sivasli H Tutkun HA Savas H Herken (2002) ArticleTitleSignificance of serotonin transporter gene 5-HTTLPR and variable number of tandem repeat polymorphism in attention deficit hyperactivity disorder Neuropsychobiology 45 176–181 Occurrence Handle12097805 Occurrence Handle10.1159/000063667 Occurrence Handle1:CAS:528:DC%2BD38XltVKks70%3D

    Article  PubMed  CAS  Google Scholar 

  • SS Zoroglu ME Erdal N Erdal S Ozen B Alasehirli E Sivasli (2003) ArticleTitleNo evidence for an association between the T102C and 1438G>A polymorphisms of the serotonin 2A receptor Gene in attention deficit/hyperactivity disorder in a Turkish population Neuropsychobiology 47 17–20 Occurrence Handle12606840 Occurrence Handle10.1159/000068870 Occurrence Handle1:CAS:528:DC%2BD3sXjtVeks7g%3D

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Child and Adolescent Psychiatry and Psychotherapy, Philipps-University, Marburg, Germany

    P. Heiser & H. Remschmidt

  2. Institute of Medical Biometry and Epidemiology, Philipps-University, Marburg, Germany

    A. Dempfle & H. Schäfer

  3. Department of Child and Adolescent Psychiatry and Psychotherapy, University of Duisburg-Essen, Essen, Germany

    S. Friedel, A. Hinney & J. Hebebrand

  4. Department of Child and Adolescent Psychiatry and Psychotherapy, RWTH, Aachen, Germany

    K. Konrad & B. Herpertz-Dahlmann

  5. Clinic for Child and Adolescent Psychiatry and Psychotherapy, Regensburg, Germany

    H. Kiefl & M. Linder

  6. Department of Child and Adolescent Psychiatry and Psychotherapy, Julius-Maximilians-University, Würzburg, Germany

    S. Walitza & A. Warnke

  7. Genome Analysis Center, GSF-National Research Center for Environment and Health, Neuherberg, Germany

    T. Bettecken

  8. Molecular Genetics and Gene Mapping Center, Max Delbrück Center, Berlin, Germany

    K. Saar

Authors
  1. P. Heiser
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Dempfle
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Friedel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. Konrad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Hinney
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H. Kiefl
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S. Walitza
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. T. Bettecken
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. K. Saar
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M. Linder
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. A. Warnke
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. B. Herpertz-Dahlmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. H. Schäfer
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. H. Remschmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. J. Hebebrand
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Heiser, P., Dempfle, A., Friedel, S. et al. Family-based association study of serotonergic candidate genes and attention-deficit/hyperactivity disorder in a German sample. J Neural Transm 114, 513–521 (2007). https://doi.org/10.1007/s00702-006-0584-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-006-0584-5

Search

Navigation