Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder

Nanda N J Rommelse, Barbara Franke, Hilde M Geurts, Catharina A Hartman, Jan K Buitelaar, Nanda N J Rommelse, Barbara Franke, Hilde M Geurts, Catharina A Hartman, Jan K Buitelaar

Abstract

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders. Evidence indicates both disorders co-occur with a high frequency, in 20-50% of children with ADHD meeting criteria for ASD and in 30-80% of ASD children meeting criteria for ADHD. This review will provide an overview on all available studies [family based, twin, candidate gene, linkage, and genome wide association (GWA) studies] shedding light on the role of shared genetic underpinnings of ADHD and ASD. It is concluded that family and twin studies do provide support for the hypothesis that ADHD and ASD originate from partly similar familial/genetic factors. Only a few candidate gene studies, linkage studies and GWA studies have specifically addressed this co-occurrence, pinpointing to some promising pleiotropic genes, loci and single nucleotide polymorphisms (SNPs), but the research field is in urgent need for better designed and powered studies to tackle this complex issue. We propose that future studies examining shared familial etiological factors for ADHD and ASD use a family-based design in which the same phenotypic (ADHD and ASD), candidate endophenotypic, and environmental measurements are obtained from all family members. Multivariate multi-level models are probably best suited for the statistical analysis.

References

    1. Allen-Brady K, Miller J, Matsunami N, Stevens J, Block H, Farley M, Krasny L, Pingree C, Lainhart J, Leppert M, McMahon WM, Coon H (2008) A high-density SNP genome-wide linkage scan in a large autism extended pedigree. Mol Psychiatry, epub ahead of print
    1. Aman MG, Farmer CA, Hollway J, Arnold LE. Treatment of inattention, overactivity, and impulsiveness in autism spectrum disorders. Child Adolesc Psychiatr Clin N Am. 2008;17:713–738. doi: 10.1016/j.chc.2008.06.009.
    1. American Psychiatric Association . Diagnostic and statistical manual of mental disorders, 4th edn, Text Revision. Washington, DC: American Psychiatric Association; 2000.
    1. Anckarsäter H, Stahlberg O, Larson T, Hakansson C, Jutblad SG, Niklasson L. The impact of ADHD and autism spectrum disorders on temperament, character, and personality development. Am J Psychiatry. 2006;163:1239–1244. doi: 10.1176/appi.ajp.163.7.1239.
    1. Anderson BM, Schnetz-Boutaud N, Bartlett J, Wright HH, Abramson RK, Cuccaro ML, Gilbert JR, Pericak-Vance MA, Haines JL. Examination of association to autism of common genetic variationin genes related to dopamine. Autism Res. 2008;1:364–369. doi: 10.1002/aur.55.
    1. Angold A, Costello EJ, Erkanli A. Comorbidity. J Child Psychol Psychiatry. 1999;40:57–87. doi: 10.1111/1469-7610.00424.
    1. Asherson P, the IMAGE Consortium Attention-deficit hyperactivity disorder in the post-genomic area. Eur Child Adolesc Psychiatry. 2004;13:50–70. doi: 10.1007/s00787-004-1006-6.
    1. Autism Genome Project Consortium. Autism genome project consortium P. Paterson AD, Zwaigenbaum L, Roberts W, Brian J, Liu XQ, Vincent JB, Skaug JL, Thompson AP, Senman L, Feuk L, Qian C, Bryson SE, Jones MB, Marshall CR, Scherer SW, Vieland VJ, Bartlett C, Mangin LV, Goedken R, Segre A, Pericak-Vance MA, Cuccaro ML, Gilbert JR, Wright HH, Abramson RK, Betancur C, Bourgeron T, Gillberg C, Leboyer M, Buxbaum JD, Davis KL, Hollander E, Silverman JM, Hallmayer J, Lotspeich L, Sutcliffe JS, Haines JL, Folstein SE, Piven J, Wassink TH, Sheffield V, Geschwind DH, Bucan M, Brown WT, Cantor RM, Constantino JN, Gilliam TC, Herbert M, Lajonchere C, Ledbetter DH, Lese-Martin C, Miller J, Nelson S, Samango-Sprouse CA, Spence S, State M, Tanzi RE, Coon H, Dawson G, Devlin B, Estes A, Flodman P, Klei L, McMahon WM, Minshew N, Munson J, Korvatska E, Rodier PM, Schellenberg GD, Smith M, Spence MA, Stodgell C, Tepper PG, Wijsman EM, Yu CE, Rogé B, Mantoulan C, Wittemeyer K, Poustka A, Felder B, Klauck SM, Schuster C, Poustka F, Bölte S, Feineis-Matthews S, Herbrecht E, Schmötzer G, Tsiantis J, Papanikolaou K, Maestrini E, Bacchelli E, Blasi F, Carone S, Toma C, Van Engeland H, de Jonge M, Kemner C, Koop F, Langemeijer M, Hijmans C, Staal WG, Baird G, Bolton PF, Rutter ML, Weisblatt E, Green J, Aldred C, Wilkinson JA, Pickles A, Le Couteur A, Berney T, McConachie H, Bailey AJ, Francis K, Honeyman G, Hutchinson A, Parr JR, Wallace S, Monaco AP, Barnby G, Kobayashi K, Lamb JA, Sousa I, Sykes N, Cook EH, Guter SJ, Leventhal BL, Salt J, Lord C, Corsello C, Hus V, Weeks DE, Volkmar F, Tauber M, Fombonne E, Shih A, Meyer KJ. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet. 2007;39:319–328. doi: 10.1038/ng1985.
    1. Bakker SC, van der Meulen EM, Buitelaar JK, Sandkuijl LA, Pauls DL, Monsuur AJ. A whole-genome scan in 164 Dutch sib pairs with attention-deficit/hyperactivity disorder: suggestive evidence for linkage on chromosomes 7p and 15q. Am J Hum Genet. 2003;72:1251–1260. doi: 10.1086/375143.
    1. Banaschewski T, Neale BM, Rothenberger A, Roessner V. Comorbidity of tic disorders and ADHD—conceptual and methodological considerations. Eur Child Adolesc Psychiatry. 2007;16(suppl 1):i5–i14. doi: 10.1007/s00787-007-1002-8.
    1. Bearden CE, Freimer NB. Endophenotypes for psychiatric disorders: ready for primetime? Trends Genet. 2006;22:306–313. doi: 10.1016/j.tig.2006.04.004.
    1. Becker K, El-Faddagh M, Schmidt MH, Esser G, Laucht M. Interaction of dopamine transporter genotype with prenatal smoke exposure on ADHD symptoms. J Pediatr. 2008;152:263–269. doi: 10.1016/j.jpeds.2007.07.004.
    1. Benyamin B, Sørensen TI, Schousboe K, Fenger M, Visscher PM, Kyvik KO. Are there common genetic and environmental factors behind the endophenotypes associated with the metabolic syndrome? Diabetologia. 2007;50:1880–1888. doi: 10.1007/s00125-007-0758-1.
    1. Bethea TC, Sikich L. Early pharmacological treatment of autism: a rationale for developmental treatment. Biol Psychiatry. 2007;61:521–537. doi: 10.1016/j.biopsych.2006.09.021.
    1. Biederman J, Newcorn J, Sprich S. Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders. Am J Psychiatry. 1991;148:564–577.
    1. Brookes K, Xu X, Chen W, Zhou K, Neale B, Lowe N, Anney R, Franke B, Gill M, Ebstein R, Buitelaar J, Sham P, Campbell D, Knight J, Andreou P, Altink M, Arnold R, Boer F, Buschgens C, Butler L, Christiansen H, Feldman L, Fleischman K, Fliers E, Howe-Forbes R, Goldfarb A, Heise A, Gabriëls I, Korn-Lubetzki I, Johansson L, Marco R, Medad S, Minderaa R, Mulas F, Müller U, Mulligan A, Rabin K, Rommelse N, Sethna V, Sorohan J, Uebel H, Psychogiou L, Weeks A, Barrett R, Craig I, Banaschewski T, Sonuga-Barke E, Eisenberg J, Kuntsi J, Manor I, McGuffin P, Miranda A, Oades RD, Plomin R, Roeyers H, Rothenberger A, Sergeant J, Steinhausen HC, Taylor E, Thompson M, Faraone SV, Asherson P. The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes. Mol Psychiatry. 2006;11:934–953. doi: 10.1038/sj.mp.4001869.
    1. Bucan M, Abrahams BS, Wang K, Glessner JT, Herman EI, Sonnenblick LI, Alvarez Retuerto AI, Imielinski M, Hadley D, Bradfield JP, Kim C, Gidaya NB, Lindquist I, Hutman T, Sigman M, Kustanovich V, Lajonchere CM, Singleton A, Kim J, Wassink TH, McMahon WM, Owley T, Sweeney JA, Coon H, Nurnberger JI, Li M, Cantor RM, Minshew NJ, Sutcliffe JS, Cook EH, Dawson G, Buxbaum JD, Grant SF, Schellenberg GD, Geschwind DH, Hakonarson H. Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes. PLoS Genet. 2009;5:e1000536. doi: 10.1371/journal.pgen.1000536.
    1. Buitelaar JK. ADHD: strategies to unravel its genetic architecture. J Neural Transm Suppl. 2005;69:1–17.
    1. Caron C, Rutter M. Comorbidity in child psychopathology: concepts, issues and research strategies. J Child Psychol Psychiatry. 1991;32:1063–1080. doi: 10.1111/j.1469-7610.1991.tb00350.x.
    1. Carpenter Rich E, Loo SK, Yang M, Dang J, Smalley SL. Social functioning difficulties in ADHD: association with PDD risk. Clin Child Psychol Psychiatry. 2009;14:329–344. doi: 10.1177/1359104508100890.
    1. Chin H, Choi SH, Jang YS, Cho SM, Kim HS, Lee JH, Jeong SW, Kim IK, Kim GJ, Kwon OJ. Protein kinase A-dependent phosphorylation of B/K protein. Exp Mol Med. 2006;38:144–152.
    1. Christian SL, Brune CW, Sudi J, Kumar RA, Liu S, Karamohamed S, Badner JA, Matsui S, Conroy J, McQuaid D, Gergel J, Hatchwell E, Gilliam TC, Gershon ES, Nowak NJ, Dobyns WB, Cook EH., Jr Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder. Biol Psychiatry. 2008;63:1111–1117. doi: 10.1016/j.biopsych.2008.01.009.
    1. Constantino JN, Hudziak JJ, Todd RD. Deficits in reciprocal social behavior in male twins: evidence for a genetically independent domain of psychopathology. J Am Acad Child Adolesc Psychiatry. 2003;42:458–467.
    1. Craig IW. The importance of stress and genetic variation in human aggression. BioEssays. 2007;29:227–236. doi: 10.1002/bies.20538.
    1. Das M, Bhowmik AD, Sinha S, Chattopadhyay A, Chaudhuri K, Singh M, Mukhopadhyay K. MAOA promoter polymorphism and attention deficit hyperactivity disorder (ADHD) in Indian children. Am J Med Genet B Neuropsychiatr Genet. 2006;141:637–642.
    1. Domschke K, Sheehan K, Lowe N, Kirley A, Mullins C, O’sullivan R, Freitag C, Becker T, Conroy J, Fitzgerald M, Gill M, Hawi Z. 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. 2005;134:110–114.
    1. Duvall JA, Lu A, Cantor RM, Todd RD, Constantino JN, Geschwindt DH. A quantitative trait locus analysis of social responsiveness in multiplex autism families. Am J Psychiatry. 2007;164:656–662. doi: 10.1176/appi.ajp.164.4.656.
    1. Elia J, Gai X, Xie HM, Perin JC, Geiger E, Glessner JT, D’arcy M, Deberardinis R, Frackelton E, Kim C, Lantieri F, Muganga BM, Wang L, Takeda T, Rappaport EF, Grant SF, Berrettini W, Devoto M, Shaikh TH, Hakonarson H, White PS (2009) Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes. Mol Psychiatry, epub ahead of print
    1. Faraone SV, Perlis RH, Doyle AE, Smoller JW, Goralnick JJ, Holmgren MA, Sklar P. Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005;57:1313–1323. doi: 10.1016/j.biopsych.2004.11.024.
    1. Farzin F, Perry H, Hessl D, Loesch D, Cohen J, Bacalman S, Gane L, Tassone F, Hagerman P, Hagerman R. Autism spectrum disorders and attention-deficit/hyperactivity disorder in boys with the fragile X permutation. J Dev Behav Pediatr. 2006;27:137–144. doi: 10.1097/00004703-200604002-00012.
    1. Franke B, Neale BM, Faraone SV (2009) Genome-wide association studies in ADHD. Hum Genet, epub ahead of print
    1. Farzin F, Perry H, Hessl D, Loesch D, Cohen J, Bacalman S, Gane L, Tassone F, Hagerman P, Hagerman R. Should the diagnosis of attention-deficit/hyperactivity disorder be considered in children with pervasive developmental disorder? J Atten Disord. 2001;4:203–211. doi: 10.1177/108705470100400402.
    1. Freitag CM. The genetics of autistic disorders and its clinical relevance: a review of the literature. Mol Psychiatry. 2007;12:2–22. doi: 10.1038/sj.mp.4001896.
    1. Gadow KD, Roohi J, DeVincent CJ, Hatchwell E. Association of ADHD, tics, and anxiety with dopamine transporter (DAT1) genotype in autism spectrum disorders. J Child Psychol Psychiatry. 2008;49:1331–1338. doi: 10.1111/j.1469-7610.2008.01952.x.
    1. Gadow KD, Roohi J, DeVincent CJ, Kirsch S, Hatchwell E (2009) Association of COMT (Val158Met) and BDNF (Val66Met) gene polymorphisms with anxiety, ADHD and tics in children with autism spectrum disorder. J Autism Dev Disord, epub ahead of print
    1. Gillberg C, Gillberg IC, Rasmussen P, Kadesjö B, Söderström H, Råstam M, Johnson M, Rothenberger A, Niklasson L. Co-existing disorders in ADHD—implications for diagnosis and intervention. Eur J Child Adolesc Psychiatry. 2004;13:80–92. doi: 10.1007/s00787-004-1008-4.
    1. Gizer IR, Ficks C, Waldman ID (2009) Candidate gene studies of ADHD: a meta-analytic review. Hum Genet, epub ahead of print
    1. Glessner JT, Wang K, Cai G, Korvatska O, Kim CE, Wood S, Zhang H, Estes A, Brune CW, Bradfield JP, Imielinski M, Frackelton EC, Reichert J, Crawford EL, Munson J, Sleiman PM, Chiavacci R, Annaiah K, Thomas K, Hou C, Glaberson W, Flory J, Otieno F, Garris M, Soorya L, Klei L, Piven J, Meyer KJ, Anagnostou E, Sakurai T, Game RM, Rudd DS, Zurawiecki D, McDougle CJ, Davis LK, Miller J, Posey DJ, Michaels S, Kolevzon A, Silverman JM, Bernier R, Levy SE, Schultz RT, Dawson G, Owley T, McMahon WM, Wassink TH, Sweeney JA, Nurnberger JI, Coon H, Sutcliffe JS, Minshew NJ, Grant SF, Bucan M, Cook EH, Buxbaum JD, Devlin B, Schellenberg GD, Hakonarson H. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature. 2009;459:569–573. doi: 10.1038/nature07953.
    1. Gould TD, Gottesman II. Psychiatric endophenotypes and the development of valid animal models. Genes Brain Behav. 2006;5:113–119. doi: 10.1111/j.1601-183X.2005.00186.x.
    1. Grady DL, Harxhi A, Smith M, Flodman P, Spence MA, Swanson JM, Moyzis RK. Sequence variants of the DRD4 gene in autism: further evidence that rare DRD4 7R haplotypes are ADHD specific. Am J Med Genet B Neuropsychiatr Genet. 2005;136B:33–35. doi: 10.1002/ajmg.b.30182.
    1. Guan L, Wang B, Chen Y, Yang L, Li J, Qian Q, Wang Z, Faraone SV, Wang Y. A high-density single-nucleotide polymorphism screen of 23 candidate genes in attention deficit hyperactivity disorder: suggesting multiple susceptibility genes among Chinese Han population. Mol Psychiatry. 2009;14:546–554. doi: 10.1038/sj.mp.4002139.
    1. Handen BL, Johnson CR, Lubetsky M. Efficacy of methylphenidate among children with autism and symptoms of attention-deficit hyperactivity disorder. J Aut Dev Disord. 2000;30:245–255. doi: 10.1023/A:1005548619694.
    1. Hattori J, Ogino T, Abiru K, Nakano K, Oka M, Ohtsuka Y. Are pervasive developmental disorders and attention-deficit/hyperactivity disorder distinct disorders? Brain Dev. 2006;28:371–374. doi: 10.1016/j.braindev.2005.11.009.
    1. Hebebrand J, Dempfle A, Saar K, Thiele H, Herpertz-Dahlmann B, Linder M. A genome-wide scan for attention-deficit/hyperactivity disorder in 155 German sib-pairs. Mol Psychiatry. 2006;11:196–205. doi: 10.1038/sj.mp.4001761.
    1. Heiser P, Friedel S, Dempfle A, Konrad K, Smidt J, Grabarkiewicz J. Molecular genetic aspects of attention-deficit/hyperactivity disorder. Neurosci Biobehav Rev. 2004;28:625–641. doi: 10.1016/j.neubiorev.2004.09.010.
    1. Hofvander B, Delorme R, Chaste P, Nydén A, Wentz E, Ståhlberg O, Herbrecht E, Stopin A, Anckarsäter H, Gillberg C, Råstam M, Leboyer M. Psychiatric and psychosocial problems in adults with normal-intelligence autism spectrum disorders. BMC Psychiatry. 2009;9:35. doi: 10.1186/1471-244X-9-35.
    1. Holtman M, Bölte S, Pousta F. Attention deficit hyperactivity disorder symptoms in pervasive developmental disorders: association with autistic behavior domains and coexisting psychopathology. Psychopathol. 2007;40:172–177. doi: 10.1159/000100007.
    1. Huang CH, Santangelo SL. Autism and serotonin transporter gene polymorphisms: a systematic review and meta-analysis. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:903–913. doi: 10.1002/ajmg.b.30720.
    1. Jain M, Palacio LG, Castellanos FX, Palacio JD, Pineda D, Restrepo MI, Muñoz JF, Lopera F, Wallis D, Berg K, Bailey-Wilson JE, Arcos-Burgos M, Muenke M. Attention-deficit/hyperactivity disorder and comorbid disruptive behavior disorders: evidence of pleiotropy and new susceptibility loci. Biol Psychiatry. 2007;61:1329–1339. doi: 10.1016/j.biopsych.2006.06.026.
    1. de Krom M, Staal WG, Ophoff RA, Hendriks J, Buitelaar J, Franke B, de Jonge MV, Bolton P, Collier D, Curran S, van Engeland H, van Ree JM. A common variant in DRD3 receptor is associated with autism spectrum disorder. Biol Psychiatry. 2009;65:625–630. doi: 10.1016/j.biopsych.2008.09.035.
    1. Lee DO, Ousley OY. Attention-deficit hyperactivity disorder symptoms in a clinic sample of children and adolescents with pervasive developmental disorders. J Child Adolesc Psychopharmacol. 2006;16:737–746. doi: 10.1089/cap.2006.16.737.
    1. Li D, Sham PC, Owen MJ, He L. Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD) Hum Mol Genet. 2006;15:2276–2284. doi: 10.1093/hmg/ddl152.
    1. Liu J, Nyholt DR, Magnussen P, Parano E, Pavone P, Geschwind D, Lord C, Iversen P, Hoh J, Ott J, Gilliam TC. A genomewide screen for autism susceptibility loci. Am J Hum Genet. 2001;69:327–340. doi: 10.1086/321980.
    1. Ma D, Salyakina D, Jaworski JM, Konidari I, Whitehead PL, Andersen AN, Hoffman JD, Slifer SH, Hedges DJ, Cukier HN, Griswold AJ, McCauley JL, Beecham GW, Wright HH, Abramson RK, Martin ER, Hussman JP, Gilbert JR, Cuccaro ML, Haines JL, Pericak-Vance MA. A genome-wide association study of autism reveals a common novel risk locus at 5p14.1. Ann Hum Genet. 2009;73:263–273. doi: 10.1111/j.1469-1809.2009.00523.x.
    1. Maher B. Personal genomes: The case of the missing heritability. Nature. 2008;456:18–21. doi: 10.1038/456018a.
    1. Manor I, Tyano S, Mel E, Eisenberg J, Bachner-Melman R, Kotler M, Ebstein RP. Family-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD): preferential transmission of the long promotor-region repeat and its association with impaired performance on a continuous performance test (TOVA) Mol Psychiatry. 2002;7:626–632. doi: 10.1038/sj.mp.4001037.
    1. Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L, Skaug J, Shago M, Moessner R, Pinto D, Ren Y, Thiruvahindrapduram B, Fiebig A, Schreiber S, Friedman J, Ketelaars CE, Vos YJ, Ficicioglu C, Kirkpatrick S, Nicolson R, Sloman L, Summers A, Gibbons CA, Teebi A, Chitayat D, Weksberg R, Thompson A, Vardy C, Crosbie V, Luscombe S, Baatjes R, Zwaigenbaum L, Roberts W, Fernandez B, Autism genome project consortium P. Scherer SW. Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet. 2008;82:477–488. doi: 10.1016/j.ajhg.2007.12.009.
    1. Mier D, Kirsch P, Meyer-Lindenberg A (2009) Neural substrates of pleiotropic action of genetic variation in COMT: a meta-analysis. Mol Psychiatry, epub ahead of print
    1. Miller DT, Shen Y, Weiss LA, Korn J, Anselm I, Bridgemohan C, Cox GF, Dickinson H, Gentile J, Harris DJ, Hegde V, Hundley R, Khwaja O, Kothare S, Luedke C, Nasir R, Poduri A, Prasad K, Raffalli P, Reinhard A, Smith SE, Sobeih MM, Soul JS, Stoler J, Takeoka M, Tan WH, Thakuria J, Wolff R, Yusupov R, Gusella JF, Daly MJ, Wu BL. Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders. J Med Genet. 2009;46:242–248. doi: 10.1136/jmg.2008.059907.
    1. Muhle R, Trentacoste SV, Rapin I. The genetics of autism. Pediatrics. 2004;113:e472–e486. doi: 10.1542/peds.113.5.e472.
    1. Mulligan A, Anney RJ, O’Regan M, Chen W, Butler L, Fitzgerald M, Buitelaar J, Steinhausen HC, Rothenberger A, Minderaa R, Nijmeijer J, Hoekstra PJ, Oades RD, Roeyers H, Buschgens C, Christiansen H, Franke B, Gabriels I, Hartman C, Kuntsi J, Marco R, Meidad S, Mueller U, Psychogiou L, Rommelse N, Thompson M, Uebel H, Banaschewski T, Ebstein R, Eisenberg J, Manor I, Miranda A, Mulas F, Sergeant J, Sonuga-Barke E, Asherson P, Faraone SV, Gill M. Autism symptoms in attention-deficit/hyperactivity disorder: a familial trait which correlates with conduct, oppositional defiant, language and motor disorders. J Autism Dev Disord. 2009;39:197–209. doi: 10.1007/s10803-008-0621-3.
    1. Munafò MR, Durrant C, Lewis G, Flint J. Gene X environment interactions at the serotonin transporter locus. Biol Psychiatry. 2009;65:211–219. doi: 10.1016/j.biopsych.2008.06.009.
    1. Neale BM, Lasky-Su J, Anney R, Franke B, Zhou K, Maller JB. Genome-wide association scan of attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:1337–1344. doi: 10.1002/ajmg.b.30866.
    1. Nijmeijer JS, Hoekstra PJ, Minderaa RB, Buitelaar JK, Altink ME, Buschgens CJ, Fliers EA, Rommelse NN, Sergeant JA, Hartman CA. PDD symptoms in ADHD, an independent familial trait? J Abnorm Child Psychol. 2008;37:443–453. doi: 10.1007/s10802-008-9282-0.
    1. Niklasson L, Rasmussen P, Oskarsdóttir S, Gillberg C. Autism, ADHD, mental retardation and behavior problems in 100 individuals with 22q11 deletion syndrome. Res Dev Disabil. 2009;30:763–773. doi: 10.1016/j.ridd.2008.10.007.
    1. Oades RD. Dopamine-serotonin interactions in attention-deficit hyperactivity disorder (ADHD) Prog Brain Res. 2008;172:543–565. doi: 10.1016/S0079-6123(08)00926-6.
    1. Ogdie MN, Macphie IL, Minassian SL, Yang M, Fisher SE, Francks C, Cantor RM, McCracken JT, McGough JJ, Nelson SF, Monaco AP, Smalley SL. A genomewide scan for attention-deficit/hyperactivity disorder in an extended sample: suggestive linkage on 17p11. Am J Hum Genet. 2003;72:1268–1279. doi: 10.1086/375139.
    1. Pamplona FA, Pandolfo P, Savoldi R, Prediger RD, Takahashi RN (2009) Environmental enrichment improves cognitive deficits in spontaneously hypertensive rats (SHR): relevance for attention deficit/hyperactivity disorder (ADHD). Prog Neuropsychopharmacol Biol Psychiatry, epub ahead of print
    1. Pickles A, Starr E, Kazak S, Bolton P, Papanikolaou K, Bailey A, Goodman R, Rutter M. Variable expression of the autism broader phenotype: findings from extended pedigrees. J Child Psychol Psychiatry. 2000;41:491–502. doi: 10.1111/1469-7610.00634.
    1. Posey DJ, Wiegand RE, Wilkerson J, Maynard M, Stigler KA, McDougle CJ. Open-label atomoxetine for attention-deficit/hyperactivity disorder symptoms associated with high-functioning pervasive developmental disorders. J Child Adolesc Psychopharmacol. 2006;16:599–610. doi: 10.1089/cap.2006.16.599.
    1. Price GW, Michie PT, Johnston J, Innes-Brown H, Kent A, Clissa P, Jablensky AV. A multivariate electrophysiological endophenotype, from a unitary cohort, shows greater research utility than any single feature in the Western Australian family study of schizophrenia. Biol Psychiatry. 2006;60:1–10. doi: 10.1016/j.biopsych.2005.09.010.
    1. Prince J. Catecholamine dysfunction in attention-deficit/hyperactivity disorder: an update. J Clin Psychopharmacol. 2008;28:S39–S45. doi: 10.1097/JCP.0b013e318174f92a.
    1. Psychiatric GWAS Consortium Coordinating Committee Genomewide association studies: history, rationale, and prospects for psychiatric disorders. Am J Psychiatry. 2009;166:540–556. doi: 10.1176/appi.ajp.2008.08091354.
    1. Psychiatric GWAS Consortium Steering Committee A framework for interpreting genome-wide association studies of psychiatric disorders. Mol Psychiatry. 2009;14:10–17. doi: 10.1038/mp.2008.126.
    1. Reiersen AM, Constantino JN, Grimmer M, Martin NG, Todd RD. Evidence for shared genetic influences on self-reported ADHD and autistic symptoms in young adult Australian twins. Twin Res Hum Genet. 2008;11:579–585. doi: 10.1375/twin.11.6.579.
    1. Retz W, Rösler M, Supprian T, Retz-Junginger P, Thome J. Dopamine D3 receptor gene polymorphism and violent behavior: relation to impulsiveness and ADHD-related psychopathology. J Neural Transm. 2003;110:561–572. doi: 10.1007/s00702-002-0805-5.
    1. Romanos M, Freitag C, Jacob C, Craig DW, Dempfle A, Nguyen TT, Halperin R, Walitza S, Renner TJ, Seitz C, Romanos J, Palmason H, Reif A, Heine M, Windemuth-Kieselbach C, Vogler C, Sigmund J, Warnke A, Schäfer H, Meyer J, Stephan DA, Lesch KP. Genome-wide linkage analysis of ADHD using high-density SNP arrays: novel loci at 5q13.1 and 14q12. Mol Psychiatry. 2008;13:522–530. doi: 10.1038/mp.2008.12.
    1. Rommelse NN, Arias-Vásquez A, Altink ME, Buschgens CJ, Fliers E, Asherson P, Faraone SV, Buitelaar JK, Sergeant JA, Oosterlaan J, Franke B. Neuropsychological endophenotype approach to genome-wide linkage analysis identifies susceptibility loci for ADHD on 2q21.1 and 13q12.11. Am J Hum Genet. 2008;83:99–105. doi: 10.1016/j.ajhg.2008.06.006.
    1. Ronald A, Simonoff E, Kuntsi J, Asherson P, Plomin R. Evidence for overlapping genetic influences on autistic and ADHD behaviours in a community twin sample. J Child Psychol Psychiatry. 2008;49:535–542. doi: 10.1111/j.1469-7610.2007.01857.x.
    1. Roohi J, DeVincent CJ, Hatchwell E, Gadow KD. Association of a monoamine oxidase-A gene promoter polymorphism with ADHD and anxiety in boys with autism spectrum disorder. J Autism Dev Disord. 2009;39:67–74. doi: 10.1007/s10803-008-0600-8.
    1. Rowlandson PH, Smith C (2009) An interagency service delivery model for autistic spectrum disorders and attention deficit hyperactivity disorder. Child Care Health Dev, epub ahead of print
    1. Sabb FW, Burggren AC, Higier RG, Fox J, He J, Parker DS, Poldrack RA, Chu W, Cannon TD, Freimer NB, Bilder RM (2009) Challenges in phenotype definition in the whole-genome era: multivariate models of memory and intelligence. Neuroscience, epub ahead of print
    1. Santosh PJ, Baird G, Pityaratstian N, Tavare E, Gringras P. Impact of comorbid autism spectrum disorders on stimulant response in children with attention deficit hyperactivity disorder: a retrospective and prospective effectiveness study. Child Care Health Dev. 2006;32:575–583. doi: 10.1111/j.1365-2214.2006.00631.x.
    1. Schellenberg GD, Dawson G, Sung YJ, Estes A, Munson J, Rosenthal E, Rothstein J, Flodman P, Smith M, Coon H, Leong L, Yu CE, Stodgell C, Rodier PM, Spence MA, Minshew N, McMahon WM, Wijsman EM. Evidence for multiple loci from a genome scan of autism kindreds. Mol Psychiatry. 2006;11:1049–1060. doi: 10.1038/sj.mp.4001874.
    1. Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, Yamrom B, Yoon S, Krasnitz A, Kendall J, Leotta A, Pai D, Zhang R, Lee YH, Hicks J, Spence SJ, Lee AT, Puura K, Lehtimäki T, Ledbetter D, Gregersen PK, Bregman J, Sutcliffe JS, Jobanputra V, Chung W, Warburton D, King MC, Skuse D, Geschwind DH, Gilliam TC, Ye K, Wigler M. Strong association of de novo copy number mutations with autism. Science. 2007;316:445–449. doi: 10.1126/science.1138659.
    1. Simonoff E, Pickles A, Charman T, Chandler S, Loucas T, Baird G. Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample. J Am Acad Child Adolesc Psychiatry. 2008;47:921–929. doi: 10.1097/CHI.0b013e318179964f.
    1. Sinzig J, Lehmkuhl G. What do we know about the serotonergic genetic heterogeneity in attention-deficit/hyperactivity and autistic disorders? Psychopathol. 2007;40:329–337. doi: 10.1159/000105531.
    1. Sinzig J, Walter D, Doepfner M (2009) Attention deficit/hyperactivity disorder in children and adolescents with autism spectrum disorder. Symptom or syndrome? J Atten Disord, epub ahead of print
    1. Smalley SL, Kustanovich V, Minassian SL, Stone JL, Ogdie MN, McGough JJ, McCracken JT, MacPhie IL, Francks C, Fisher SE, Cantor RM, Monaco AP, Nelson SF. Genetic linkage of attention-deficit/hyperactivity disorder on chromosome 16p13, in a region implicated in autism. Am J Hum Genet. 2002;71:959–963. doi: 10.1086/342732.
    1. Sonuga-Barke EJ, Oades RD, Psychogiou L, Chen W, Franke B, Buitelaar J (2009) Dopamine and serotonin transporter genotypes moderate sensitivity to maternal expressed emotion: the case of conduct and emotional problems in attention deficit/hyperactivity disorder. J Child Psychol Psychiatry, epub ahead of print
    1. Steyaert JG, De la Marche W. What’s new in autism? Eur J Pediatr. 2008;167:1091–1101. doi: 10.1007/s00431-008-0764-4.
    1. Tartaglia N, Davis S, Hench A, Nimishakavi S, Beauregard R, Reynolds A, Fenton L, Albrecht L, Ross J, Visootsak J, Hansen R, Hagerman R. A new look at XXYY syndrome: medical and psychological features. Am J Med Genet A. 2008;146A:1509–1522. doi: 10.1002/ajmg.a.32366.
    1. Trikalinos TA, Karvouni A, Zintzaras E, Ylisaukko-oja T, Peltonen L, Jarvela I, Ioannidis JP. A heterogeneity-based genome search meta-analysis for autism spectrum disorders. Mol Psychiatry. 2006;11:29–36. doi: 10.1038/sj.mp.4001750.
    1. Tripp G, Wickens JR (2009) Neurobiology of ADHD. Neuropharmacology, epub ahead of print
    1. Troost PW, Steenhuis MP, Tuynman-Qua HG, Kalverdijk LJ, Buitelaar JK, Minderaa RB, Hoekstra PJ. Atomoxetine for attention-deficit/hyperactivity disorder symptoms in children with pervasive developmental disorders: a pilot study. J Child Adolesc Psychopharmacol. 2006;16:611–619. doi: 10.1089/cap.2006.16.611.
    1. Wang K, Zhang H, Ma D, Bucan M, Glessner JT, Abrahams BS, Salyakina D, Imielinski M, Bradfield JP, Sleiman PM, Kim CE, Hou C, Frackelton E, Chiavacci R, Takahashi N, Sakurai T, Rappaport E, Lajonchere CM, Munson J, Estes A, Korvatska O, Piven J, Sonnenblick LI, Alvarez Retuerto AI, Herman EI, Dong H, Hutman T, Sigman M, Ozonoff S, Klin A, Owley T, Sweeney JA, Brune CW, Cantor RM, Bernier R, Gilbert JR, Cuccaro ML, McMahon WM, Miller J, State MW, Wassink TH, Coon H, Levy SE, Schultz RT, Nurnberger JI, Haines JL, Sutcliffe JS, Cook EH, Minshew NJ, Buxbaum JD, Dawson G, Grant SF, Geschwind DH, Pericak-Vance MA, Schellenberg GD, Hakonarson H. Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature. 2009;459:528–533. doi: 10.1038/nature07999.
    1. Warren DM, Dyer TD, Peterson CP, Mahaney MC, Blangero J, Almasy L. A comparison of univariate, bivariate, and trivariate whole-genome linkage screens of genetically correlated electrophysiological endophenotypes. BMC Genet. 2005;6(Suppl 1):S117. doi: 10.1186/1471-2156-6-S1-S117.
    1. Weiss LA, Shen Y, Korn JM, Arking DE, Miller DT, Fossdal R, Saemundsen E, Stefansson H, Ferreira MA, Green T, Platt OS, Ruderfer DM, Walsh CA, Altshuler D, Chakravarti A, Tanzi RE, Stefansson K, Santangelo SL, Gusella JF, Sklar P, Wu BL, Daly MJ, Consortium Autism. Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med. 2008;358:667–675. doi: 10.1056/NEJMoa075974.
    1. Yonan AL, Alarcón M, Cheng R, Magnusson PK, Spence SJ, Palmer AA, Grunn A, Juo SH, Terwilliger JD, Liu J, Cantor RM, Geschwind DH, Gilliam TC. A genomewide screen of 345 families for autism-susceptibility loci. Am J Hum Genet. 2003;73:886–897. doi: 10.1086/378778.
    1. Yoshida Y, Uchiyama T. The clinical necessity for assessing attention deficit/hyperactivity disorder (AD/HD) symptoms in children with high-functioning pervasive developmental disorder (PDD) Eur Child Adolesc Psychiatry. 2004;13:307–314. doi: 10.1007/s00787-004-0391-1.
    1. Zhou K, Dempfle A, Arcos-Burgos M, Bakker SC, Banaschewski T, Biederman J. Meta-analysis of genome-wide linkage scans of attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:1392–1398. doi: 10.1002/ajmg.b.30878.
    1. van der Zwaag B, Franke L, Poot M, Hochstenbach R, Spierenburg HA, Vorstman JA, van Daalen E, de Jonge MV, Verbeek NE, Brilstra EH, van ‘t Slot R, Ophoff RA, van Es MA, Blauw HM, Veldink JH, Buizer-Voskamp JE, Beemer FA, van den Berg LH, Wijmenga C, van Amstel HK, van Engeland H, Burbach JP, Staal WG. Gene-network analysis identifies susceptibility genes related to glycobiology in autism. PLoS One. 2009;4:e5324. doi: 10.1371/journal.pone.0005324.

Source: PubMed

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