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Neurotrophic factor-related gene polymorphisms and adult attention deficit hyperactivity disorder (ADHD) score in a high-risk male population

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Conner, Alex C., Kissling, Christian, Hodges, Edward, Huennerkopf, Regina, Clement, R. Marc, Dudley, E. (Edward), Freitag, Christine M., Roesler, Michael, Retz, Wolfgang and Thome, Johannes. (2008) Neurotrophic factor-related gene polymorphisms and adult attention deficit hyperactivity disorder (ADHD) score in a high-risk male population. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics , Vol.147B (No.8 ). pp. 1476-1480. ISSN 1552-4841

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Official URL: http://dx.doi.org/10.1002/ajmg.b.30632

Abstract

Adult attention deficit hyperactivity disorder (ADHD) is a widely under-reported but nevertheless common condition with a clear heritable component. Several genes have been proposed to play a role in the childhood onset of this neuro-developmental disorder; however, association studies of persistence of ADHD into adulthood have rarely been per-formed. Neurotrophic factors (NTFs) are known to be involved in several aspects of neuronal development and neural plasticity in adults. They have also been linked, particularly through brain-derived neurotrophic factor (BDNF) interaction with dopamine transport, to the pathophysiology of ADHD. This study compares the genotypes of six different single nucleotide polymorphisms of genes within the neurotrophin system and their possible association with adult ADHD score in 143 high-risk male subjects referred to a forensic psychiatric unit. The genes included NTF3 NTRK2 (TrkB), NTRK3 (TrkC), BDNF, and p75(NTR). While none of the SNPs showed significant association with ADHD symptoms, one polymorphism within the exon of NTF3 (rs6332) showed a trend toward an association between the A-allele and increased scores using both the retrospective childhood analysis Wender-Utah Rating Scale (WURS-k) (P=0.05) and the adult ADHD assessment Wender-Reimherr interview (P = 0.03). This SNP is a silent mutation which might be in linkage disequilibrium with a functional risk variant for ADHD. As the association was only suggestive, however, this finding needs replication in a larger study with higher power. (c) 2008 Wiley-Liss, Inc.

Item Type:

Journal Article

Subjects:

Q Science > QH Natural history > QH426 Genetics
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry

Divisions:

Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016)
Faculty of Medicine > Warwick Medical School

Library of Congress Subject Headings (LCSH):

Attention-deficit disorder in adults, Neurotrophic functions, Chromosome polymorphism, Human genetics -- Variation, Genetic markers, Genetic epidemiology

Journal or Publication Title:

American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

Publisher:

John Wiley & Sons, Inc.

ISSN:

1552-4841

Official Date:

5 December 2008

Dates:

Date	Event
5 December 2008	Published

Volume:

Vol.147B

Number:

No.8

Number of Pages:

Page Range:

pp. 1476-1480

Identification Number:

10.1002/ajmg.b.30632

Status:

Peer Reviewed

Publication Status:

Published

Access rights to Published version:

Restricted or Subscription Access

Funder:

Deutsche Forschungsgemeinschaft (DFG)

Grant number:

DFG HU1536/1-1 (DFG)

References:

Adler CM, Delbello MP, Mills NP, Schmithorst V, Holland S, Strakowski
SM. 2005. Comorbid ADHD is associated with altered patterns of
neuronal activation in adolescents with bipolar disorder performing a
simple attention task. Bipolar Disord 7(6):577–588.
Barkley RA, Fischer M, Smallish L, Fletcher K. 2002. The persistence of
attention-deficit/hyperactivity disorder into young adulthood as a
function of reporting source and definition of disorder. J Abnorm Psychol
111(2):279–289.
Barkley RA, Murphy JV. 1978. Pseudodeterioration of intelligence in
children. Ann Neurol 4(4):388.
Biederman J, Faraone SV, Keenan K, Knee D, Tsuang MT. 1990. Familygenetic
and psychosocial risk factors in DSM-III attention deficit
disorder. J Am Acad Child Adolesc Psychiatry 29(4):526–533.
Blochl A, Blochl R. 2007. A cell-biological model of p75(NTR) signaling.
J Neurochem 102: 289–305.
Brown RT, Freeman WS, Perrin JM, Stein MT, Amler RW, Feldman HM,
Pierce K, Wolraich ML. 2001. Prevalence and assessment of attentiondeficit/
hyperactivity disorder in primary care settings.Pediatrics 107(3):
E43.
Domschke K, Sheehan K, Lowe N, Kirley A, MullinsC,O’Sullivan R, Freitag
C, Becker T, Conroy J, Fitzgerald M, et al. 2005. Association 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 134B(1):110–114.
Dvornyk V, Long JR,Xiong DH, Liu PY, Zhao LJ, ShenH, Zhang YY, Liu YJ,
Rocha-Sanchez S, Xiao P, et al. 2004. Current limitations of SNP data
from the public domain for studies of complex disorders: A test for ten
candidate genes for obesity and osteoporosis. BMC Genet 5:4.
Faraone SV, Perlis RH, Doyle AE, Smoller JW, Goralnick JJ, Holmgren MA,
Sklar P. 2005. Molecular genetics of attention-deficit/hyperactivity
disorder. Biol Psychiatry 57(11):1313–1323.
Feng Y, Crosbie J, Wigg K, Pathare T, Ickowicz A, Schachar R, Tannock R,
Roberts W, Malone M, Swanson J, Kennedy JL, Barr CL. The SNAP25
gene as a susceptibility gene contributing to attention-deficit hyperactivity
disorder. Mol Psychiatry 2005. 10(11):998–1005, 973.
Hattori M, Kunugi H, Akahane A, Tanaka H, Ishida S, Hirose T, Morita R,
Yamakawa K, Nanko S. 2002. Novel polymorphisms in the promoter
region of the neurotrophin-3 gene and their associations with schizophrenia.
Am J Med Genet 114(3):304–309.
Hu¨ nnerkopf R, Strobel A, Gutknecht L, Brocke B, Lesch KP. 2007.
Interaction between BDNF Val66Met and dopamine transporter gene
variation influences anxiety-related traits. Neuropsychopharmacology
32: 2552–2560.
Kent L, Green E, Hawi Z, Kirley A, Dudbridge F, Lowe N, Raybould R,
Langley K, Bray N, Fitzgerald M, et al. 2005. Association of the
paternally transmitted copy of common valine allele of the Val66Met
polymorphism of the brain-derived neurotrophic factor (BDNF) gene
with susceptibility to ADHD. Mol Psychiatry 10(10):939–943.
Kissling C, Retz W, Wiemann S, Coogan A, Clement R, Hu¨ nnerkopf R,
ConnerA, FreitagC,Ro¨sler M, Thome J. 2007.Apolymorphism at the 30-
untranslated region of the clock gene is associated with adult attentiondeficit
hyperactivity disorder. AmJ Med Genet BNeuropsychiatr Genet
(in press).
Kordon A, Kahl KG, WahlK. 2006. A new understanding of attention-deficit
disorders-beyond the age-at-onset criterion of DSM-IV. Eur Arch
Psychiatry Clin Neurosci 256 (Suppl 1):i47–i54.
Kustanovich V, MerrimanB, Mcgough J, Mccracken JT, Smalley SL, Nelson
SF. 2003. Biased paternal transmission of SNAP-25 risk alleles in
attention-deficit hyperactivity disorder. Mol Psychiatry 8(3):309–315.
Lynch G, Kramar EA, Rex CS, Jia Y, Chappas D, Gall CM, Simmons DA.
2007. Brain-derived neurotrophic factor restores synaptic plasticity in a
knock-inmouse model of Huntington’s disease. JNeurosci 27(16):4424–
4434.
Monteggia LM, Barrot M, Powell CM, Berton O, Galanis V, Gemelli T,
Meuth S, Nagy A, Greene RW, Nestler EJ. 2004. Essential role of brainderived
neurotrophic factor in adult hippocampal function. Proc Natl
Acad Sci USA 101(29):10827–10832.
Monteggia LM, Luikart B, Barrot M, Theobold D, Malkovska I, Nef S,
Parada LF, Nestler EJ. 2007. Brain-derived neurotrophic factor conditional
knockouts show gender differences in depression-related behaviors.
Biol Psychiatry 61(2):187–197.
Neuman RJ, Heath A, Reich W, Bucholz KK, Madden PAF, Sun L, Todd RD,
Hudziak JJ. 2001. Latent class analysis of ADHD and comorbid
symptoms in a population sample of adolescent female twins. J Child
Psychol Psychiatry 42(7):933–942.
Retz W, Retz-Junginger P, Supprian T, Thome J, Ro¨sler M. 2004.
Association of serotonin promoter gene polymorphism with violence:
Relation with personality disorders, impulsivity and childhood ADHD
psychopathology. Behav Sci Law 22(3):415–425.
Retz-Junginger P, Retz W, Blocher D, Stieglitz RD, Georg T, Supprian T,
Wender PH, Ro¨sler M. 2003. Reliability and validity of the Wender–
Utah-rating-scale short form.Retrospective assessment of symptoms for
attention deficit/hyperactivity disorder. Nervenarzt 74(11):987–993.
Ro¨sler M, RetzW,Retz-Junginger P, Hengesch G, Schneider M, Supprian T,
Schwitzgebel P, Pinhard K, Dovi-Akue N, Wender P. et al. 2004.
Prevalence of attention deficit-/hyperactivity disorder (ADHD) and
comorbid disorders in young male prison inmates. Eur Arch Psychiatry
Clin Neurosci 254(6):365–371.
Ro¨sler M, Retz W, Thome J, Schneider M, Stieglitz RD, Falkai P. 2006.
Psychopathological rating scales for diagnostic use in adults with
attention-deficit/hyperactivity disorder (ADHD). Eur Arch Psychiatry
Clin Neurosci 256 (Suppl 1):i3–i11.
Rowland AS, Lesesne CA, Abramowitz AJ. 2002. The epidemiology of
attention-deficit/hyperactivity disorder (ADHD): A public health view.
Ment Retard Dev Disabil Res Rev 8(3):162–170.
Schimmelmann BG, Friedel S, Dempfle A, Warnke A, Lesch KP, Walitza S,
Renner TJ, Romanos M, Herpertz-Dahlmann B, Linder M, et al. 2007.
No evidence for preferential transmission of common valine allele of the
Val66Met polymorphism of the brain-derived neurotrophic factor gene
(BDNF) in ADHD. J Neural Transm 114(4):523–526.
Syed Z, Dudbridge F, Kent L. 2007. An investigation of the neurotrophic
factor genes GDNF, NGF, andNT3 in susceptibility to ADHD.AmJ Med
Genet B Neuropsychiatr Genet 144B(3):375–378.
Thapar A, Langley K, O’Donovan M, Owen M. 2006. Refining the attention
deficit hyperactivity disorder phenotype for molecular genetic studies.
Mol Psychiatry 11(8):714–720.
Thapar A, Langley K, Owen MJ, O’Donovan MC. 2007. Advances in genetic
findings on attention deficit hyperactivity disorder. Psychol Med 37:
1681–1692.
Thome J, Durany N, Palomo A, Foley P, Harsanyi A, Baumer A, Hashimoto
E, Cruz-Sanchez FF, Riederer P. 1997. Variants in neurotrophic factor
genes and schizophrenic psychoses: No associations in a Spanish
population. Psychiatry Res 71(1):1–5.
Tsai SJ. 2007. Attention-deficit hyperactivity disorder may be associated
with decreased central brain-derived neurotrophic factor activity:
Clinical and therapeutic implications. Med Hypotheses 68(4):896–
899.
Ward MF, Wender PH, Reimherr FW. 1993. The Wender Utah rating scale:
An aid in the retrospective diagnosis of childhood attention deficit
hyperactivity disorder. Am J Psychiatry 150(6):885–890.
Wender EH. 1995. Attention-deficit hyperactivity disorders in adolescence.
J Dev Behav Pediatr 16(3):192–195.