Skip to main content

Advertisement

SpringerLink
Log in

Applying Imaging Genetics to ADHD: the Promises and the Challenges

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Attention deficit/hyperactivity disorder (ADHD) is one of the most prevalent childhood psychiatric disorders. During the past decades, studies have focused on its genetic background and the abnormality of the brain structure and function. Recently, an advanced technique linking these two areas, namely, the imaging genetics emerged and kept growing. Imaging genetics primarily identifies genes that influence the brain variations. There are three main strategies of doing an imaging genetic study: using neuroimaging as endophenotypes to find the associated DNA variants, finding neuroimaging effects of risk genes, and hypothesis-free whole-brain voxelwise genome-wide association study. In this review, we begin with demonstrating the basic principles of imaging genetics precisely, with examples from other psychiatric conditions, and then go on to synthesize the existing imaging genetic studies in ADHD. Finally, we elaborate the challenges of applying imaging genetics to ADHD. We conclude that imaging genetics has somewhat showed its potential to provide a more precise understanding of how the genes shape the brain variations and further the clinical features 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

References

  1. 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. doi:10.1016/j.biopsych.2004.11.024

    PubMed  CAS  Google Scholar 

  2. Sun H, Yuan F, Shen X, Xiong G, Wu J (2013) Role of COMT in ADHD: a systematic meta-analysis. Mol Neurobiol. doi:10.1007/s12035-013-8516-5

    Google Scholar 

  3. Faraone SV, Doyle AE, Mick E, Biederman J (2001) Meta-analysis of the association between the 7-repeat allele of the dopamine D (4) receptor gene and attention deficit hyperactivity disorder. Am J Psychiatry 158(7):1052–1057

    PubMed  CAS  Google Scholar 

  4. Faraone SV, Khan SA (2006) Candidate gene studies of attention-deficit/hyperactivity disorder. J Clin Psychiatry 67(Suppl 8):13–20

    PubMed  CAS  Google Scholar 

  5. Faraone SV, Mick E (2010) Molecular genetics of attention deficit hyperactivity disorder. Psychiatr Clin N Am 33(1):159–180. doi:10.1016/j.psc.2009.12.004

    Google Scholar 

  6. Lesch KP, Timmesfeld N, Renner TJ, Halperin R, Roser C, Nguyen TT, Craig DW, Romanos J, Heine M, Meyer J, Freitag C, Warnke A, Romanos M, Schafer H, Walitza S, Reif A, Stephan DA, Jacob C (2008) Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies. J Neural Transm 115(11):1573–1585. doi:10.1007/s00702-008-0119-3

    PubMed  CAS  Google Scholar 

  7. Neale BM, Lasky-Su J, Anney R, Franke B, Zhou K, Maller JB, Vasquez AA, Asherson P, Chen W, Banaschewski T, Buitelaar J, Ebstein R, Gill M, Miranda A, Oades RD, Roeyers H, Rothenberger A, Sergeant J, Steinhausen HC, Sonuga-Barke E, Mulas F, Taylor E, Laird N, Lange C, Daly M, Faraone SV (2008) Genome-wide association scan of attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 147B(8):1337–1344. doi:10.1002/ajmg.b.30866

    PubMed  CAS  PubMed Central  Google Scholar 

  8. Mick E, Todorov A, Smalley S, Hu X, Loo S, Todd RD, Biederman J, Byrne D, Dechairo B, Guiney A, McCracken J, McGough J, Nelson SF, Reiersen AM, Wilens TE, Wozniak J, Neale BM, Faraone SV (2010) Family-based genome-wide association scan of attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 49(9):898–905. doi:10.1016/j.jaac.2010.02.014, e893

    PubMed  PubMed Central  Google Scholar 

  9. Neale BM, Medland S, Ripke S, Anney RJ, Asherson P, Buitelaar J, Franke B, Gill M, Kent L, Holmans P, Middleton F, Thapar A, Lesch KP, Faraone SV, Daly M, Nguyen TT, Schafer H, Steinhausen HC, Reif A, Renner TJ, Romanos M, Romanos J, Warnke A, Walitza S, Freitag C, Meyer J, Palmason H, Rothenberger A, Hawi Z, Sergeant J, Roeyers H, Mick E, Biederman J, Group IIC (2010) Case–control genome-wide association study of attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 49(9):906–920. doi:10.1016/j.jaac.2010.06.007

    PubMed  PubMed Central  Google Scholar 

  10. Hinney A, Scherag A, Jarick I, Albayrak O, Putter C, Pechlivanis S, Dauvermann MR, Beck S, Weber H, Scherag S, Nguyen TT, Volckmar AL, Knoll N, Faraone SV, Neale BM, Franke B, Cichon S, Hoffmann P, Nothen MM, Schreiber S, Jockel KH, Wichmann HE, Freitag C, Lempp T, Meyer J, Gilsbach S, Herpertz-Dahlmann B, Sinzig J, Lehmkuhl G, Renner TJ, Warnke A, Romanos M, Lesch KP, Reif A, Schimmelmann BG, Hebebrand J, Psychiatric GCAs (2011) Genome-wide association study in German patients with attention deficit/hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 156B(8):888–897. doi:10.1002/ajmg.b.31246

    PubMed  Google Scholar 

  11. Stergiakouli E, Hamshere M, Holmans P, Langley K, Zaharieva I, de CG, Psychiatric GC, Hawi Z, Kent L, Gill M, Williams N, Owen MJ, O’Donovan M, Thapar A (2012) Investigating the contribution of common genetic variants to the risk and pathogenesis of ADHD. The American journal of psychiatry 169 (2):186–194

    Google Scholar 

  12. Yang L, Neale BM, Liu L, Lee SH, Wray NR, Ji N, Li H, Qian Q, Wang D, Li J, Faraone SV, Wang Y, Psychiatric GCAS, Doyle AE, Reif A, Rothenberger A, Franke B, Sonuga-Barke EJ, Steinhausen HC, Buitelaar JK, Kuntsi J, Biederman J, Lesch KP, Kent L, Asherson P, Oades RD, Loo SK, Nelson SF, Faraone SV, Smalley SL, Banaschewski T, Arias Vasquez A, Todorov A, Charach A, Miranda A, Warnke A, Thapar A, Neale BM, Cormand B, Freitag C, Mick E, Mulas F, Middleton F, HakonarsonHakonarson H, Palmason H, Schafer H, Roeyers H, McGough JJ, Romanos J, Crosbie J, Meyer J, Ramos-Quiroga JA, Sergeant J, Elia J, Langely K, Nisenbaum L, Romanos M, Daly MJ, Ribases M, Gill M, O’Donovan M, Owen M, Casas M, Bayes M, Lambregts-Rommelse N, Williams N, Holmans P, Anney RJ, Ebstein RP, Schachar R, Medland SE, Ripke S, Walitza S, Nguyen TT, Renner TJ, Hu X (2013) Polygenic transmission and complex neuro developmental network for attention deficit hyperactivity disorder: genome-wide association study of both common and rare variants. Am J Med Genet B Neuropsychiatr Genet 162B(5):419–430. doi:10.1002/ajmg.b.32169

    PubMed  Google Scholar 

  13. Glahn DC, Thompson PM, Blangero J (2007) Neuroimaging endophenotypes: strategies for finding genes influencing brain structure and function. Hum Brain Mapp 28(6):488–501. doi:10.1002/hbm.20401

    PubMed  Google Scholar 

  14. McCarthy H, Skokauskas N, Frodl T (2013) Identifying a consistent pattern of neural function in attention deficit hyperactivity disorder: a meta-analysis. Psychological medicine:1–12. doi:10.1017/S0033291713001037

  15. Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K (2013) Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects. JAMA Psychiatry 70(2):185–198. doi:10.1001/jamapsychiatry.2013.277

    PubMed  Google Scholar 

  16. Ellison-Wright I, Ellison-Wright Z, Bullmore E (2008) Structural brain change in attention deficit hyperactivity disorder identified by meta-analysis. BMC Psychiatr 8:51. doi:10.1186/1471-244X-8-51

    Google Scholar 

  17. van Ewijk H, Heslenfeld DJ, Zwiers MP, Buitelaar JK, Oosterlaan J (2012) Diffusion tensor imaging in attention deficit/hyperactivity disorder: a systematic review and meta-analysis. Neurosci Biobehav Rev 36(4):1093–1106. doi:10.1016/j.neubiorev.2012.01.003

    PubMed  Google Scholar 

  18. Cao Q, Shu N, An L, Wang P, Sun L, Xia MR, Wang JH, Gong GL, Zang YF, Wang YF, He Y (2013) Probabilistic diffusion tractography and graph theory analysis reveal abnormal white matter structural connectivity networks in drug-naive boys with attention deficit/hyperactivity disorder. J Neurosci Off J Soc Neurosci 33(26):10676–10687. doi:10.1523/JNEUROSCI.4793-12.2013

    CAS  Google Scholar 

  19. Wang L, Zhu C, He Y, Zang Y, Cao Q, Zhang H, Zhong Q, Wang Y (2009) Altered small-world brain functional networks in children with attention-deficit/hyperactivity disorder. Hum Brain Mapp 30(2):638–649. doi:10.1002/hbm.20530

    PubMed  CAS  Google Scholar 

  20. McCarthy H, Skokauskas N, Mulligan A, Donohoe G, Mullins D, Kelly J, Johnson K, Fagan A, Gill M, Meaney J, Frodl T (2013) Attention network hypoconnectivity with default and affective network hyperconnectivity in adults diagnosed with attention-deficit/hyperactivity disorder in childhood. JAMA Psychiatry 70(12):1329–1337. doi:10.1001/jamapsychiatry.2013.2174

    PubMed  Google Scholar 

  21. Castellanos FX, Proal E (2012) Large-scale brain systems in ADHD: beyond the prefrontal-striatal model. Trends Cogn Sci 16(1):17–26. doi:10.1016/j.tics.2011.11.007

    PubMed  PubMed Central  Google Scholar 

  22. Blokland GA, de Zubicaray GI, McMahon KL, Wright MJ (2012) Genetic and environmental influences on neuroimaging phenotypes: a meta-analytical perspective on twin imaging studies. Twin Res Human Genet Official J Int Soc Twin Stud 15(3):351–371. doi:10.1017/thg.2012.11

    Google Scholar 

  23. den Braber A, Bohlken MM, Brouwer RM, Van ‘t Ent D, Kanai R, Kahn RS, de Geus EJ, Hulshoff Pol HE, Boomsma DI (2013) Heritability of subcortical brain measures: a perspective for future genome-wide association studies. NeuroImage 83:98–102. doi:10.1016/j.neuroimage.2013.06.027

    Google Scholar 

  24. Bryant C, Giovanello KS, Ibrahim JG, Chang J, Shen D, Peterson BS, Zhu H, Alzheimer’s Disease Neuroimaging I (2013) Mapping the genetic variation of regional brain volumes as explained by all common SNPs from the ADNI study. PLoS ONE 8(8):e71723. doi:10.1371/journal.pone.0071723

    PubMed  CAS  PubMed Central  Google Scholar 

  25. Blokland GA, McMahon KL, Thompson PM, Martin NG, de Zubicaray GI, Wright MJ (2011) Heritability of working memory brain activation. J Neurosci Off J Soc Neurosci 31(30):10882–10890. doi:10.1523/JNEUROSCI.5334-10.2011

    CAS  Google Scholar 

  26. Cote C, Beauregard M, Girard A, Mensour B, Mancini-Marie A, Perusse D (2007) Individual variation in neural correlates of sadness in children: a twin fMRI study. Hum Brain Mapp 28(6):482–487. doi:10.1002/hbm.20400

    PubMed  Google Scholar 

  27. Matthews SC, Simmons AN, Strigo I, Jang K, Stein MB, Paulus MP (2007) Heritability of anterior cingulate response to conflict: an fMRI study in female twins. NeuroImage 38(1):223–227. doi:10.1016/j.neuroimage.2007.07.015

    PubMed  Google Scholar 

  28. Polk TA, Park J, Smith MR, Park DC (2007) Nature versus nurture in ventral visual cortex: a functional magnetic resonance imaging study of twins. J Neurosci Off J Soc Neurosci 27(51):13921–13925. doi:10.1523/JNEUROSCI.4001-07.2007

    CAS  Google Scholar 

  29. van den Heuvel MP, van Soelen IL, Stam CJ, Kahn RS, Boomsma DI, Hulshoff Pol HE (2013) Genetic control of functional brain network efficiency in children. Eur Neuropsychopharmacol J Euro Coll Neuropsychopharmacol 23(1):19–23. doi:10.1016/j.euroneuro.2012.06.007

    Google Scholar 

  30. Fornito A, Zalesky A, Bassett DS, Meunier D, Ellison-Wright I, Yucel M, Wood SJ, Shaw K, O’Connor J, Nertney D, Mowry BJ, Pantelis C, Bullmore ET (2011) Genetic influences on cost-efficient organization of human cortical functional networks. J Neurosci Off J Soc Neurosci 31(9):3261–3270. doi:10.1523/JNEUROSCI.4858-10.2011

    CAS  Google Scholar 

  31. Chen CH, Gutierrez ED, Thompson W, Panizzon MS, Jernigan TL, Eyler LT, Fennema-Notestine C, Jak AJ, Neale MC, Franz CE, Lyons MJ, Grant MD, Fischl B, Seidman LJ, Tsuang MT, Kremen WS, Dale AM (2012) Hierarchical genetic organization of human cortical surface area. Science 335(6076):1634–1636. doi:10.1126/science.1215330

    PubMed  CAS  PubMed Central  Google Scholar 

  32. Liu Y, Spulber G, Lehtimaki KK, Kononen M, Hallikainen I, Grohn H, Kivipelto M, Hallikainen M, Vanninen R, Soininen H (2011) Diffusion tensor imaging and tract-based spatial statistics in Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging 32(9):1558–1571. doi:10.1016/j.neurobiolaging.2009.10.006

    PubMed  Google Scholar 

  33. Stricker NH, Schweinsburg BC, Delano-Wood L, Wierenga CE, Bangen KJ, Haaland KY, Frank LR, Salmon DP, Bondi MW (2009) Decreased white matter integrity in late-myelinating fiber pathways in Alzheimer’s disease supports retrogenesis. NeuroImage 45(1):10–16. doi:10.1016/j.neuroimage.2008.11.027

    PubMed  CAS  PubMed Central  Google Scholar 

  34. Lee AD LN, Barysheva M, Chou Y-Y, Brun CC, Madsen SK et al (2008) Gene effects mapped using fractional and geodesic anisotropy in diffusion tensor images of 92 monozygotic and dizygotic twins. Paper presented at the MICCAI Workshop on Computational Diffusion MRI,

  35. Chiang MC, Barysheva M, Shattuck DW, Lee AD, Madsen SK, Avedissian C, Klunder AD, Toga AW, McMahon KL, de Zubicaray GI, Wright MJ, Srivastava A, Balov N, Thompson PM (2009) Genetics of brain fiber architecture and intellectual performance. J Neurosci Off J Soc Neurosci 29(7):2212–2224. doi:10.1523/JNEUROSCI.4184-08.2009

    CAS  Google Scholar 

  36. Kochunov P, Glahn DC, Lancaster JL, Winkler AM, Smith S, Thompson PM, Almasy L, Duggirala R, Fox PT, Blangero J (2010) Genetics of microstructure of cerebral white matter using diffusion tensor imaging. NeuroImage 53(3):1109–1116. doi:10.1016/j.neuroimage.2010.01.078

    PubMed  CAS  PubMed Central  Google Scholar 

  37. Lee AD LN, de Leeuw J, Brun CC, Barysheva M, McMahon KL et al (2010) Multivariate variance-components analysis in DTI. Paper presented at the IEEE International Symposium on Biomedical Imaging,

  38. Patel V CM-C, Thompson PM, McMahon KL, de Zubicaray GI, Martin NG et al (2010) Scalar connectivity measures from fast marching tractography reveal heritability of white matter architecture. Paper presented at the IEEE International Symposium on Biomedical Imaging,

  39. Chiang MC, McMahon KL, de Zubicaray GI, Martin NG, Hickie I, Toga AW, Wright MJ, Thompson PM (2011) Genetics of white matter development: a DTI study of 705 twins and their siblings aged 12 to 29. NeuroImage 54(3):2308–2317. doi:10.1016/j.neuroimage.2010.10.015

    PubMed  PubMed Central  Google Scholar 

  40. Chiang MC, Barysheva M, Toga AW, Medland SE, Hansell NK, James MR, McMahon KL, de Zubicaray GI, Martin NG, Wright MJ, Thompson PM (2011) BDNF gene effects on brain circuitry replicated in 455 twins. NeuroImage 55(2):448–454. doi:10.1016/j.neuroimage.2010.12.053

    PubMed  CAS  PubMed Central  Google Scholar 

  41. Braskie MN, Jahanshad N, Stein JL, Barysheva M, Johnson K, McMahon KL, de Zubicaray GI, Martin NG, Wright MJ, Ringman JM, Toga AW, Thompson PM (2012) Relationship of a variant in the NTRK1 gene to white matter microstructure in young adults. J Neurosci Off J Soc Neurosci 32(17):5964–5972. doi:10.1523/JNEUROSCI.5561-11.2012

    CAS  Google Scholar 

  42. Konrad A, Vucurevic G, Musso F, Stoeter P, Dahmen N, Winterer G (2009) ErbB4 genotype predicts left frontotemporal structural connectivity in human brain. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 34(3):641–650. doi:10.1038/npp.2008.112

    CAS  Google Scholar 

  43. Jahanshad N, Kohannim O, Hibar DP, Stein JL, McMahon KL, de Zubicaray GI, Medland SE, Montgomery GW, Whitfield JB, Martin NG, Wright MJ, Toga AW, Thompson PM (2012) Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in the HFE gene. Proc Natl Acad Sci U S A 109(14):E851–E859. doi:10.1073/pnas.1105543109

    PubMed  CAS  PubMed Central  Google Scholar 

  44. Thomason ME, Dougherty RF, Colich NL, Perry LM, Rykhlevskaia EI, Louro HM, Hallmayer JF, Waugh CE, Bammer R, Glover GH, Gotlib IH (2010) COMT genotype affects prefrontal white matter pathways in children and adolescents. NeuroImage 53(3):926–934. doi:10.1016/j.neuroimage.2010.01.033

    PubMed  CAS  PubMed Central  Google Scholar 

  45. Kohannim O, Jahanshad N, Braskie MN, Stein JL, Chiang MC, Reese AH, Hibar DP, Toga AW, McMahon KL, de Zubicaray GI, Medland SE, Montgomery GW, Martin NG, Wright MJ, Thompson PM (2012) Predicting white matter integrity from multiple common genetic variants. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 37(9):2012–2019. doi:10.1038/npp.2012.49

    CAS  Google Scholar 

  46. Stein JL, Hua X, Morra JH, Lee S, Hibar DP, Ho AJ, Leow AD, Toga AW, Sul JH, Kang HM, Eskin E, Saykin AJ, Shen L, Foroud T, Pankratz N, Huentelman MJ, Craig DW, Gerber JD, Allen AN, Corneveaux JJ, Stephan DA, Webster J, DeChairo BM, Potkin SG, Jack CR Jr, Weiner MW, Thompson PM, Alzheimer’s Disease Neuroimaging I (2010) Genome-wide analysis reveals novel genes influencing temporal lobe structure with relevance to neurodegeneration in Alzheimer’s disease. NeuroImage 51(2):542–554. doi:10.1016/j.neuroimage.2010.02.068

    PubMed  CAS  PubMed Central  Google Scholar 

  47. Stein JL, Hibar DP, Madsen SK, Khamis M, McMahon KL, de Zubicaray GI, Hansell NK, Montgomery GW, Martin NG, Wright MJ, Saykin AJ, Jack CR Jr, Weiner MW, Toga AW, Thompson PM, Alzheimer’s Disease Neuroimaging Initiative I (2011) Discovery and replication of dopamine-related gene effects on caudate volume in young and elderly populations (N = 1198) using genome-wide search. Mol Psychiatry 16(9):927–937. doi:10.1038/mp.2011.32, 881

    PubMed  CAS  PubMed Central  Google Scholar 

  48. Stein JL, Medland SE, Vasquez AA, Hibar DP, Senstad RE, Winkler AM, Toro R, Appel K, Bartecek R, Bergmann O, Bernard M, Brown AA, Cannon DM, Chakravarty MM, Christoforou A, Domin M, Grimm O, Hollinshead M, Holmes AJ, Homuth G, Hottenga JJ, Langan C, Lopez LM, Hansell NK, Hwang KS, Kim S, Laje G, Lee PH, Liu X, Loth E, Lourdusamy A, Mattingsdal M, Mohnke S, Maniega SM, Nho K, Nugent AC, O’Brien C, Papmeyer M, Putz B, Ramasamy A, Rasmussen J, Rijpkema M, Risacher SL, Roddey JC, Rose EJ, Ryten M, Shen L, Sprooten E, Strengman E, Teumer A, Trabzuni D, Turner J, van Eijk K, van Erp TG, van Tol MJ, Wittfeld K, Wolf C, Woudstra S, Aleman A, Alhusaini S, Almasy L, Binder EB, Brohawn DG, Cantor RM, Carless MA, Corvin A, Czisch M, Curran JE, Davies G, de Almeida MA, Delanty N, Depondt C, Duggirala R, Dyer TD, Erk S, Fagerness J, Fox PT, Freimer NB, Gill M, Goring HH, Hagler DJ, Hoehn D, Holsboer F, Hoogman M, Hosten N, Jahanshad N, Johnson MP, Kasperaviciute D, Kent JW Jr, Kochunov P, Lancaster JL, Lawrie SM, Liewald DC, Mandl R, Matarin M, Mattheisen M, Meisenzahl E, Melle I, Moses EK, Muhleisen TW, Nauck M, Nothen MM, Olvera RL, Pandolfo M, Pike GB, Puls R, Reinvang I, Renteria ME, Rietschel M, Roffman JL, Royle NA, Rujescu D, Savitz J, Schnack HG, Schnell K, Seiferth N, Smith C, Steen VM, Valdes Hernandez MC, Van den Heuvel M, van der Wee NJ, Van Haren NE, Veltman JA, Volzke H, Walker R, Westlye LT, Whelan CD, Agartz I, Boomsma DI, Cavalleri GL, Dale AM, Djurovic S, Drevets WC, Hagoort P, Hall J, Heinz A, Jack CR Jr, Foroud TM, Le Hellard S, Macciardi F, Montgomery GW, Poline JB, Porteous DJ, Sisodiya SM, Starr JM, Sussmann J, Toga AW, Veltman DJ, Walter H, Weiner MW, Alzheimer’s Disease Neuroimaging I, Consortium E, Consortium I, Saguenay Youth Study G, Bis JC, Ikram MA, Smith AV, Gudnason V, Tzourio C, Vernooij MW, Launer LJ, DeCarli C, Seshadri S, Cohorts for H, Aging Research in Genomic Epidemiology C, Andreassen OA, Apostolova LG, Bastin ME, Blangero J, Brunner HG, Buckner RL, Cichon S, Coppola G, de Zubicaray GI, Deary IJ, Donohoe G, de Geus EJ, Espeseth T, Fernandez G, Glahn DC, Grabe HJ, Hardy J, Hulshoff Pol HE, Jenkinson M, Kahn RS, McDonald C, McIntosh AM, McMahon FJ, McMahon KL, Meyer-Lindenberg A, Morris DW, Muller-Myhsok B, Nichols TE, Ophoff RA, Paus T, Pausova Z, Penninx BW, Potkin SG, Samann PG, Saykin AJ, Schumann G, Smoller JW, Wardlaw JM, Weale ME, Martin NG, Franke B, Wright MJ, Thompson PM, Thompson PM, Thompson PM, Thompson PM, Thompson PM, Thompson PM, Enhancing Neuro Imaging Genetics through Meta-Analysis C (2012) Identification of common variants associated with human hippocampal and intracranial volumes. Nat Genet 44(5):552–561. doi:10.1038/ng.2250

    PubMed  CAS  PubMed Central  Google Scholar 

  49. Jahanshad N, Rajagopalan P, Hua X, Hibar DP, Nir TM, Toga AW, Jack CR Jr, Saykin AJ, Green RC, Weiner MW, Medland SE, Montgomery GW, Hansell NK, McMahon KL, de Zubicaray GI, Martin NG, Wright MJ, Thompson PM, Alzheimer’s Disease Neuroimaging I (2013) Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity. Proc Natl Acad Sci U S A 110(12):4768–4773. doi:10.1073/pnas.1216206110

    PubMed  CAS  PubMed Central  Google Scholar 

  50. Hariri AR, Weinberger DR (2003) Imaging genomics. Br Med Bull 65:259–270

    PubMed  CAS  Google Scholar 

  51. Dennis EL, Jahanshad N, Rudie JD, Brown JA, Johnson K, McMahon KL, de Zubicaray GI, Montgomery G, Martin NG, Wright MJ, Bookheimer SY, Dapretto M, Toga AW, Thompson PM (2011) Altered structural brain connectivity in healthy carriers of the autism risk gene, CNTNAP2. Brain connect 1(6):447–459. doi:10.1089/brain.2011.0064

    PubMed  PubMed Central  Google Scholar 

  52. Clemm von Hohenberg C, Wigand MC, Kubicki M, Leicht G, Giegling I, Karch S, Hartmann AM, Konte B, Friedl M, Ballinger T, Eckbo R, Bouix S, Jager L, Shenton ME, Rujescu D, Mulert C (2013) CNTNAP2 polymorphisms and structural brain connectivity: a diffusion-tensor imaging study. J Psychiatr Res 47(10):1349–1356. doi:10.1016/j.jpsychires.2013.07.002

    PubMed  Google Scholar 

  53. Whalley HC, O’Connell G, Sussmann JE, Peel A, Stanfield AC, Hayiou-Thomas ME, Johnstone EC, Lawrie SM, McIntosh AM, Hall J (2011) Genetic variation in CNTNAP2 alters brain function during linguistic processing in healthy individuals. Am J Med Genet B Neuropsychiatr Genet 156B(8):941–948. doi:10.1002/ajmg.b.31241

    PubMed  Google Scholar 

  54. Scott-Van Zeeland AA, Abrahams BS, Alvarez-Retuerto AI, Sonnenblick LI, Rudie JD, Ghahremani D, Mumford JA, Poldrack RA, Dapretto M, Geschwind DH, Bookheimer SY (2010) Altered functional connectivity in frontal lobe circuits is associated with variation in the autism risk gene CNTNAP2. Sci Transl Med 2(56):56–80. doi:10.1126/scitranslmed.3001344

    Google Scholar 

  55. Bertram L, McQueen MB, Mullin K, Blacker D, Tanzi RE (2007) Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet 39(1):17–23. doi:10.1038/ng1934

    PubMed  CAS  Google Scholar 

  56. Dati G, Quattrini A, Bernasconi L, Malaguti MC, Antonsson B, Nicoletti F, Alliod C, Di Marco R, Sagot Y, Vitte PA, Hiver A, Greco B, Roach A, Zaratin PF (2007) Beneficial effects of r-h-CLU on disease severity in different animal models of peripheral neuropathies. J Neuroimmunol 190(1–2):8–17. doi:10.1016/j.jneuroim.2007.07.014

    PubMed  CAS  Google Scholar 

  57. Braskie MN, Jahanshad N, Stein JL, Barysheva M, McMahon KL, de Zubicaray GI, Martin NG, Wright MJ, Ringman JM, Toga AW, Thompson PM (2011) Common Alzheimer’s disease risk variant within the CLU gene affects white matter microstructure in young adults. J Neurosci Off J Soc Neurosci 31(18):6764–6770. doi:10.1523/JNEUROSCI.5794-10.2011

    CAS  Google Scholar 

  58. Hibar DP, Stein JL, Kohannim O, Jahanshad N, Saykin AJ, Shen L, Kim S, Pankratz N, Foroud T, Huentelman MJ, Potkin SG, Jack CR Jr, Weiner MW, Toga AW, Thompson PM, Alzheimer’s Disease Neuroimaging I (2011) Voxelwise gene-wide association study (vGeneWAS): multivariate gene-based association testing in 731 elderly subjects. NeuroImage 56(4):1875–1891. doi:10.1016/j.neuroimage.2011.03.077

    PubMed  PubMed Central  Google Scholar 

  59. Durston S (2010) Imaging genetics in ADHD. NeuroImage 53(3):832–838. doi:10.1016/j.neuroimage.2010.02.071

    PubMed  CAS  Google Scholar 

  60. Nikolaidis A, Gray JR (2010) ADHD and the DRD4 exon III 7-repeat polymorphism: an international meta-analysis. Soc Cogn Affect Neurosci 5(2–3):188–193. doi:10.1093/scan/nsp049

    PubMed  PubMed Central  Google Scholar 

  61. Gornick MC, Addington A, Shaw P, Bobb AJ, Sharp W, Greenstein D, Arepalli S, Castellanos FX, Rapoport JL (2007) Association of the dopamine receptor D4 (DRD4) gene 7-repeat allele with children with attention-deficit/hyperactivity disorder (ADHD): an update. Am J Med Genet B Neuropsychiatr Genet 144B(3):379–382. doi:10.1002/ajmg.b.30460

    PubMed  CAS  Google Scholar 

  62. Shaw P, Gornick M, Lerch J, Addington A, Seal J, Greenstein D, Sharp W, Evans A, Giedd JN, Castellanos FX, Rapoport JL (2007) Polymorphisms of the dopamine D4 receptor, clinical outcome, and cortical structure in attention-deficit/hyperactivity disorder. Arch Gen Psychiatr 64(8):921–931. doi:10.1001/archpsyc.64.8.921

    PubMed  Google Scholar 

  63. Monuteaux MC, Seidman LJ, Faraone SV, Makris N, Spencer T, Valera E, Brown A, Bush G, Doyle AE, Hughes S, Helliesen M, Mick E, Biederman J (2008) A preliminary study of dopamine D4 receptor genotype and structural brain alterations in adults with ADHD. Am J Med Genet B Neuropsychiatr Genet 147B(8):1436–1441. doi:10.1002/ajmg.b.30870

    PubMed  CAS  Google Scholar 

  64. Bobb AJ, Addington AM, Sidransky E, Gornick MC, Lerch JP, Greenstein DK, Clasen LS, Sharp WS, Inoff-Germain G, Wavrant-De Vrieze F, Arcos-Burgos M, Straub RE, Hardy JA, Castellanos FX, Rapoport JL (2005) Support for association between ADHD and two candidate genes: NET1 and DRD1. Am J Med Genet B Neuropsychiatr Genet 134B(1):67–72. doi:10.1002/ajmg.b.30142

    PubMed  Google Scholar 

  65. Shook D, Brady C, Lee PS, Kenealy L, Murphy ER, Gaillard WD, VanMeter JW, Cook EH Jr, Stein M, Vaidya CJ (2011) Effect of dopamine transporter genotype on caudate volume in childhood ADHD and controls. Am J Med Genet B Neuropsychiatr Genet 156B(1):28–35. doi:10.1002/ajmg.b.31132

    PubMed  PubMed Central  Google Scholar 

  66. Buckner RL, Andrews-Hanna JR, Schacter DL (2008) The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 1124:1–38. doi:10.1196/annals.1440.011

    PubMed  Google Scholar 

  67. Crawford AA, Lewis G, Lewis SJ, Munafo MR (2013) Systematic review and meta-analysis of serotonin transporter genotype and discontinuation from antidepressant treatment. Eur Neuropsychopharmacol J Euro Coll Neuropsychopharmacol 23(10):1143–1150. doi:10.1016/j.euroneuro.2012.12.001

    CAS  Google Scholar 

  68. Chen X, Margolis KJ, Gershon MD, Schwartz GJ, Sze JY (2012) Reduced serotonin reuptake transporter (SERT) function causes insulin resistance and hepatic steatosis independent of food intake. PLoS ONE 7(3):e32511. doi:10.1371/journal.pone.0032511

    PubMed  CAS  PubMed Central  Google Scholar 

  69. Cerasa A, Quattrone A, Piras F, Mangone G, Magariello A, Fagioli S, Girardi P, Muglia M, Caltagirone C, Spalletta G (2013) 5-HTTLPR, anxiety and gender interaction moderates right amygdala volume in healthy subjects. Soc Cogn Affect Neurosci. doi:10.1093/scan/nst144

    PubMed  Google Scholar 

  70. Sala-Llonch R, Pena-Gomez C, Arenaza-Urquijo EM, Vidal-Pineiro D, Bargallo N, Junque C, Bartres-Faz D (2012) Brain connectivity during resting state and subsequent working memory task predicts behavioural performance. Cortex; a journal devoted to the study of the nervous system and behavior 48(9):1187–1196. doi:10.1016/j.cortex.2011.07.006

    PubMed  Google Scholar 

  71. Stern ER, Fitzgerald KD, Welsh RC, Abelson JL, Taylor SF (2012) Resting-state functional connectivity between fronto-parietal and default mode networks in obsessive-compulsive disorder. PLoS ONE 7(5):e36356. doi:10.1371/journal.pone.0036356

    PubMed  CAS  PubMed Central  Google Scholar 

  72. Wiggins JL, Bedoyan JK, Peltier SJ, Ashinoff S, Carrasco M, Weng SJ, Welsh RC, Martin DM, Monk CS (2012) The impact of serotonin transporter (5-HTTLPR) genotype on the development of resting-state functional connectivity in children and adolescents: a preliminary report. NeuroImage 59(3):2760–2770. doi:10.1016/j.neuroimage.2011.10.030

    PubMed  CAS  PubMed Central  Google Scholar 

  73. Genro JP, Kieling C, Rohde LA, Hutz MH (2010) Attention-deficit/hyperactivity disorder and the dopaminergic hypotheses. Expert Rev Neurother 10(4):587–601. doi:10.1586/ern.10.17

    PubMed  CAS  Google Scholar 

  74. Paloyelis Y, Mehta MA, Faraone SV, Asherson P, Kuntsi J (2012) Striatal sensitivity during reward processing in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 51(7):722–732. doi:10.1016/j.jaac.2012.05.006, e729

    PubMed  PubMed Central  Google Scholar 

  75. Hoogman M, Onnink M, Cools R, Aarts E, Kan C, Arias Vasquez A, Buitelaar J, Franke B (2013) The dopamine transporter haplotype and reward-related striatal responses in adult ADHD. Eur Neuropsychopharmacol J Euro Coll Neuropsychopharmacol 23(6):469–478. doi:10.1016/j.euroneuro.2012.05.011

    CAS  Google Scholar 

  76. Aarts E, Roelofs A, Franke B, Rijpkema M, Fernandez G, Helmich RC, Cools R (2010) Striatal dopamine mediates the interface between motivational and cognitive control in humans: evidence from genetic imaging. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 35(9):1943–1951. doi:10.1038/npp.2010.68

    CAS  Google Scholar 

  77. Dreher JC, Kohn P, Kolachana B, Weinberger DR, Berman KF (2009) Variation in dopamine genes influences responsivity of the human reward system. Proc Natl Acad Sci U S A 106(2):617–622. doi:10.1073/pnas.0805517106

    PubMed  CAS  PubMed Central  Google Scholar 

  78. Hahn T, Heinzel S, Dresler T, Plichta MM, Renner TJ, Markulin F, Jakob PM, Lesch KP, Fallgatter AJ (2011) Association between reward-related activation in the ventral striatum and trait reward sensitivity is moderated by dopamine transporter genotype. Hum Brain Mapp 32(10):1557–1565. doi:10.1002/hbm.21127

    PubMed  Google Scholar 

  79. Forbes EE, Brown SM, Kimak M, Ferrell RE, Manuck SB, Hariri AR (2009) Genetic variation in components of dopamine neurotransmission impacts ventral striatal reactivity associated with impulsivity. Mol Psychiatry 14(1):60–70. doi:10.1038/sj.mp.4002086

    PubMed  CAS  PubMed Central  Google Scholar 

  80. Stice E, Yokum S, Burger K, Epstein L, Smolen A (2012) Multilocus genetic composite reflecting dopamine signaling capacity predicts reward circuitry responsivity. J Neurosci Off J Soc Neurosci 32(29):10093–10100. doi:10.1523/JNEUROSCI.1506-12.2012

    CAS  Google Scholar 

  81. Hoogman M, Aarts E, Zwiers M, Slaats-Willemse D, Naber M, Onnink M, Cools R, Kan C, Buitelaar J, Franke B (2011) Nitric oxide synthase genotype modulation of impulsivity and ventral striatal activity in adult ADHD patients and healthy comparison subjects. Am J Psychiatry 168(10):1099–1106. doi:10.1176/appi.ajp.2011.10101446

    PubMed  Google Scholar 

  82. Lesch KP, Selch S, Renner TJ, Jacob C, Nguyen TT, Hahn T, Romanos M, Walitza S, Shoichet S, Dempfle A, Heine M, Boreatti-Hummer A, Romanos J, Gross-Lesch S, Zerlaut H, Wultsch T, Heinzel S, Fassnacht M, Fallgatter A, Allolio B, Schafer H, Warnke A, Reif A, Ropers HH, Ullmann R (2011) Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: association with neuropeptide Y gene dosage in an extended pedigree. Mol Psychiatry 16(5):491–503. doi:10.1038/mp.2010.29

    PubMed  CAS  Google Scholar 

  83. Nymberg C, Jia T, Lubbe S, Ruggeri B, Desrivieres S, Barker G, Buchel C, Fauth-Buehler M, Cattrell A, Conrod P, Flor H, Gallinat J, Garavan H, Heinz A, Ittermann B, Lawrence C, Mann K, Nees F, Salatino-Oliveira A, Paillere Martinot ML, Paus T, Rietschel M, Robbins T, Smolka M, Banaschewski T, Rubia K, Loth E, Schumann G, Consortium I (2013) Neural mechanisms of attention-deficit/hyperactivity disorder symptoms are stratified by MAOA genotype. Biol Psychiatry 74(8):607–614. doi:10.1016/j.biopsych.2013.03.027

    Google Scholar 

  84. Stollstorff M, Foss-Feig J, Cook EH Jr, Stein MA, Gaillard WD, Vaidya CJ (2010) Neural response to working memory load varies by dopamine transporter genotype in children. NeuroImage 53(3):970–977. doi:10.1016/j.neuroimage.2009.12.104

    PubMed  CAS  PubMed Central  Google Scholar 

  85. Gordon EM, Devaney JM, Bean S, Vaidya CJ (2013) Resting-state striato-frontal functional connectivity is sensitive to DAT1 genotype and predicts executive function. Cereb Cortex. doi:10.1093/cercor/bht229

    Google Scholar 

  86. Whitfield-Gabrieli S, Thermenos HW, Milanovic S, Tsuang MT, Faraone SV, McCarley RW, Shenton ME, Green AI, Nieto-Castanon A, LaViolette P, Wojcik J, Gabrieli JD, Seidman LJ (2009) Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia. Proc Natl Acad Sci U S A 106(4):1279–1284. doi:10.1073/pnas.0809141106

    PubMed  CAS  PubMed Central  Google Scholar 

  87. Anticevic A, Repovs G, Shulman GL, Barch DM (2010) When less is more: TPJ and default network deactivation during encoding predicts working memory performance. NeuroImage 49(3):2638–2648. doi:10.1016/j.neuroimage.2009.11.008

    PubMed  PubMed Central  Google Scholar 

  88. Sun YW, Qin LD, Zhou Y, Xu Q, Qian LJ, Tao J, Xu JR (2011) Abnormal functional connectivity in patients with vascular cognitive impairment, no dementia: a resting-state functional magnetic resonance imaging study. Behav Brain Res 223(2):388–394. doi:10.1016/j.bbr.2011.05.006

    PubMed  Google Scholar 

  89. Wilson TW, Franzen JD, Heinrichs-Graham E, White ML, Knott NL, Wetzel MW (2013) Broadband neurophysiological abnormalities in the medial prefrontal region of the default-mode network in adults with ADHD. Hum Brain Mapp 34(3):566–574. doi:10.1002/hbm.21459

    PubMed  Google Scholar 

  90. Jucaite A, Fernell E, Halldin C, Forssberg H, Farde L (2005) Reduced midbrain dopamine transporter binding in male adolescents with attention-deficit/hyperactivity disorder: association between striatal dopamine markers and motor hyperactivity. Biol Psychiatry 57(3):229–238. doi:10.1016/j.biopsych.2004.11.009

    PubMed  CAS  Google Scholar 

  91. Hannestad J, Gallezot JD, Planeta-Wilson B, Lin SF, Williams WA, van Dyck CH, Malison RT, Carson RE, Ding YS (2010) Clinically relevant doses of methylphenidate significantly occupy norepinephrine transporters in humans in vivo. Biol Psychiatry 68(9):854–860. doi:10.1016/j.biopsych.2010.06.017

    PubMed  CAS  PubMed Central  Google Scholar 

  92. Brown AB, Biederman J, Valera E, Makris N, Doyle A, Whitfield-Gabrieli S, Mick E, Spencer T, Faraone S, Seidman L (2011) Relationship of DAT1 and adult ADHD to task-positive and task-negative working memory networks. Psychiatry Res 193(1):7–16. doi:10.1016/j.pscychresns.2011.01.006

    PubMed  PubMed Central  Google Scholar 

  93. Krause J (2008) SPECT and PET of the dopamine transporter in attention-deficit/hyperactivity disorder. Expert Rev Neurother 8(4):611–625. doi:10.1586/14737175.8.4.611

    PubMed  CAS  Google Scholar 

  94. Durston S, Mulder M, Casey BJ, Ziermans T, van Engeland H (2006) Activation in ventral prefrontal cortex is sensitive to genetic vulnerability for attention-deficit hyperactivity disorder. Biol Psychiatry 60(10):1062–1070. doi:10.1016/j.biopsych.2005.12.020

    PubMed  CAS  Google Scholar 

  95. Braet W, Johnson KA, Tobin CT, Acheson R, McDonnell C, Hawi Z, Barry E, Mulligan A, Gill M, Bellgrove MA, Robertson IH, Garavan H (2011) fMRI activation during response inhibition and error processing: the role of the DAT1 gene in typically developing adolescents and those diagnosed with ADHD. Neuropsychologia 49(7):1641–1650. doi:10.1016/j.neuropsychologia.2011.01.001

    PubMed  Google Scholar 

  96. Durston S, Fossella JA, Mulder MJ, Casey BJ, Ziermans TB, Vessaz MN, Van Engeland H (2008) Dopamine transporter genotype conveys familial risk of attention-deficit/hyperactivity disorder through striatal activation. J Am Acad Child Adolesc Psychiatry 47(1):61–67. doi:10.1097/chi.0b013e31815a5f17

    PubMed  Google Scholar 

  97. Bedard AC, Schulz KP, Cook EH Jr, Fan J, Clerkin SM, Ivanov I, Halperin JM, Newcorn JH (2010) Dopamine transporter gene variation modulates activation of striatum in youth with ADHD. NeuroImage 53(3):935–942. doi:10.1016/j.neuroimage.2009.12.041

    PubMed  CAS  PubMed Central  Google Scholar 

  98. Cummins TD, Hawi Z, Hocking J, Strudwick M, Hester R, Garavan H, Wagner J, Chambers CD, Bellgrove MA (2012) Dopamine transporter genotype predicts behavioural and neural measures of response inhibition. Mol Psychiatry 17(11):1086–1092. doi:10.1038/mp.2011.104

    PubMed  CAS  Google Scholar 

  99. Whelan R, Conrod PJ, Poline JB, Lourdusamy A, Banaschewski T, Barker GJ, Bellgrove MA, Buchel C, Byrne M, Cummins TD, Fauth-Buhler M, Flor H, Gallinat J, Heinz A, Ittermann B, Mann K, Martinot JL, Lalor EC, Lathrop M, Loth E, Nees F, Paus T, Rietschel M, Smolka MN, Spanagel R, Stephens DN, Struve M, Thyreau B, Vollstaedt-Klein S, Robbins TW, Schumann G, Garavan H, Consortium I (2012) Adolescent impulsivity phenotypes characterized by distinct brain networks. Nat Neurosci 15(6):920–925. doi:10.1038/nn.3092

    Google Scholar 

  100. Reif A, Jacob CP, Rujescu D, Herterich S, Lang S, Gutknecht L, Baehne CG, Strobel A, Freitag CM, Giegling I, Romanos M, Hartmann A, Rosler M, Renner TJ, Fallgatter AJ, Retz W, Ehlis AC, Lesch KP (2009) Influence of functional variant of neuronal nitric oxide synthase on impulsive behaviors in humans. Arch Gen Psychiatr 66(1):41–50. doi:10.1001/archgenpsychiatry.2008.510

    PubMed  CAS  Google Scholar 

  101. Fallgatter AJ, Ehlis AC, Dresler T, Reif A, Jacob CP, Arcos-Burgos M, Muenke M, Lesch KP (2013) Influence of a latrophilin 3 (LPHN3) risk haplotype on event-related potential measures of cognitive response control in attention-deficit hyperactivity disorder (ADHD). Eur Neuropsychopharmacol J Euro Coll Neuropsychopharmacol 23(6):458–468. doi:10.1016/j.euroneuro.2012.11.001

    CAS  Google Scholar 

  102. Heinzel S, Dresler T, Baehne CG, Heine M, Boreatti-Hummer A, Jacob CP, Renner TJ, Reif A, Lesch KP, Fallgatter AJ, Ehlis AC (2013) COMT x DRD4 epistasis impacts prefrontal cortex function underlying response control. Cereb Cortex 23(6):1453–1462. doi:10.1093/cercor/bhs132

    PubMed  Google Scholar 

  103. Baehne CG, Ehlis AC, Plichta MM, Conzelmann A, Pauli P, Jacob C, Gutknecht L, Lesch KP, Fallgatter AJ (2009) Tph2 gene variants modulate response control processes in adult ADHD patients and healthy individuals. Mol Psychiatry 14(11):1032–1039. doi:10.1038/mp.2008.39

    PubMed  CAS  Google Scholar 

  104. Rivero O, Sich S, Popp S, Schmitt A, Franke B, Lesch KP (2013) Impact of the ADHD-susceptibility gene CDH13 on development and function of brain networks. Eur Neuropsychopharmacol J Euro Coll Neuropsychopharmacol 23(6):492–507. doi:10.1016/j.euroneuro.2012.06.009

    CAS  Google Scholar 

  105. Akutagava-Martins GC, Salatino-Oliveira A, Kieling CC, Rohde LA, Hutz MH (2013) Genetics of attention-deficit/hyperactivity disorder: current findings and future directions. Expert Rev Neurother 13(4):435–445. doi:10.1586/ern.13.30

    PubMed  CAS  Google Scholar 

  106. Shaw P, Malek M, Watson B, Sharp W, Evans A, Greenstein D (2012) Development of cortical surface area and gyrification in attention-deficit/hyperactivity disorder. Biol Psychiatry 72(3):191–197. doi:10.1016/j.biopsych.2012.01.031

    PubMed  Google Scholar 

  107. Yang XR, Carrey N, Bernier D, Macmaster FP (2012) Cortical thickness in young treatment-naive children with ADHD. J Atten Disord. doi:10.1177/1087054712455501

    Google Scholar 

  108. Shaw P, Eckstrand K, Sharp W, Blumenthal J, Lerch JP, Greenstein D, Clasen L, Evans A, Giedd J, Rapoport JL (2007) Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proc Natl Acad Sci U S A 104(49):19649–19654. doi:10.1073/pnas.0707741104

    PubMed  CAS  PubMed Central  Google Scholar 

  109. Varrone A, Halldin C (2010) Molecular imaging of the dopamine transporter. J Nucl Med Off Publ Soc Nucl Med 51(9):1331–1334. doi:10.2967/jnumed.109.065656

    CAS  Google Scholar 

  110. Volkow ND, Fowler JS, Wang G, Ding Y, Gatley SJ (2002) Mechanism of action of methylphenidate: insights from PET imaging studies. J Atten Disord 6(Suppl 1):S31–S43

    PubMed  Google Scholar 

  111. Greenbaum L, Lorberboym M, Melamed E, Rigbi A, Barhum Y, Kohn Y, Khlebtovsky A, Lerer B, Djaldetti R (2013) Perspective: identification of genetic variants associated with dopaminergic compensatory mechanisms in early Parkinson’s disease. Front Neurosci 7:52. doi:10.3389/fnins.2013.00052

    PubMed  PubMed Central  Google Scholar 

  112. Hibar DP, Kohannim O, Stein JL, Chiang MC, Thompson PM (2011) Multilocus genetic analysis of brain images. Front Genet 2:73. doi:10.3389/fgene.2011.00073

    PubMed  PubMed Central  Google Scholar 

  113. Rubenstein JL (2011) Annual research review: development of the cerebral cortex: implications for neurodevelopmental disorders. J Child Psychol Psychiatry Allied Discip 52(4):339–355. doi:10.1111/j.1469-7610.2010.02307.x

    Google Scholar 

  114. Lenroot RK, Giedd JN (2008) The changing impact of genes and environment on brain development during childhood and adolescence: initial findings from a neuroimaging study of pediatric twins. Dev Psychopathol 20(4):1161–1175. doi:10.1017/S0954579408000552

    PubMed  PubMed Central  Google Scholar 

  115. Meyer-Lindenberg A, Nicodemus KK, Egan MF, Callicott JH, Mattay V, Weinberger DR (2008) False positives in imaging genetics. NeuroImage 40(2):655–661. doi:10.1016/j.neuroimage.2007.11.058

    PubMed  Google Scholar 

  116. Ge T, Feng J, Hibar DP, Thompson PM, Nichols TE (2012) Increasing power for voxel-wise genome-wide association studies: the random field theory, least square kernel machines and fast permutation procedures. NeuroImage 63(2):858–873. doi:10.1016/j.neuroimage.2012.07.012

    PubMed  PubMed Central  Google Scholar 

  117. de Geus E, Goldberg T, Boomsma DI, Posthuma D (2008) Imaging the genetics of brain structure and function. Biol Psychol 79(1):1–8. doi:10.1016/j.biopsycho.2008.04.002

    PubMed  Google Scholar 

  118. Ball RD (2013) Designing a GWAS: power, sample size, and data structure. Methods Mol Biol 1019:37–98. doi:10.1007/978-1-62703-447-0_3

    PubMed  Google Scholar 

  119. Evans DM, Purcell S (2012) Power calculations in genetic studies. Cold Spring Harb Protoc 2012(6):664–674. doi:10.1101/pdb.top069559

    PubMed  Google Scholar 

  120. Poline JB LC TA, France E, Thirion B, Frouin V (2010) Imaging genetics: bio-informatics and bio-statistics challenges. Paper presented at the 19th international conference on computational statistics, Paris, France

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Peking University Sixth Hospital/Institute of Mental Health, Beijing, China

    Zhaomin Wu, Li Yang & Yufeng Wang

  2. Key Laboratory of Mental Health, Ministry of Health, Beijing, China

    Zhaomin Wu, Li Yang & Yufeng Wang

Authors
  1. Zhaomin Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Li Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yufeng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Li Yang or Yufeng Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wu, Z., Yang, L. & Wang, Y. Applying Imaging Genetics to ADHD: the Promises and the Challenges. Mol Neurobiol 50, 449–462 (2014). https://doi.org/10.1007/s12035-014-8683-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-014-8683-z

Keywords

Search

Navigation