Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Psychiatry Reports
Published in: Current Psychiatry Reports 11/2014

01-11-2014 | Attention-Deficit Disorder (A Rostain, Section Editor)

Biomarkers in the Diagnosis of ADHD – Promising Directions

Authors: Stephen V. Faraone, Cristian Bonvicini, Catia Scassellati

Published in: Current Psychiatry Reports | Issue 11/2014

Login to get access

Abstract

The etiology and pathogenesis of attention-deficit/hyperactivity disorder (ADHD) are unclear and a more valid diagnosis would certainly be welcomed. Starting from the literature, we built an hypothetical pyramid representing a putative set of biomarkers where, at the top, variants in DAT1 and DRD4 genes are the best candidates for their associations to neuropsychological tasks, activation in specific brain areas, methylphenidate response and gene expression levels. Interesting data come from the noradrenergic system (norepinephrine transporter, norepinephrine, 3-methoxy-4-hydroxyphenylglycol, monoamine oxidase, neuropeptide Y) for their altered peripheral levels, their association with neuropsychological tasks, symptomatology, drugs effect and brain function. Other minor putative genetic biomarkers could be dopamine beta hydroxylase and catechol-O-methyltransferase. In the bottom, we placed endophenotype biomarkers. A more deep integration of “omics” sciences along with more accurate clinical profiles and new high-throughput computational methods will allow us to identify a better list of biomarkers useful for diagnosis and therapies.
Literature
1.
Biederman J, Faraone SV. Attention-deficit hyperactivity disorder. Lancet. 2005;366(9481):237–48.PubMedCrossRef
2.
Faraone SV. Attention-deficit hyperactivity disorder and the shifting sands of psychiatric nosology. Br J Psychiatr. 2013;203(2):81–3.CrossRef
3.
Faraone SV, Mick E. Molecular genetics of attention deficit hyperactivity disorder. Psychiatr Clin N Am. 2010;33(1):159–80.CrossRef
4.••
Akutagava-Martins GC, Salatino-Oliveira A, Kieling CC, Rohde LA, Hutz MH. Genetics of attention-deficit/hyperactivity disorder: current findings and future directions. Expert Rev Neurother. 2013;13(4):435–45. This is an exhaustive review on the genetics studies in ADHD. It summarized that all variants associated with the pathology explain only a small fraction of heritability: phenotype complexity and variants of small effect contribute to the missing heritability issue.PubMedCrossRef
5.
Gould TD, Manji HK. The molecular medicine revolution and psychiatry: bridging the gap between basic neuroscience research and clinical psychiatry. J Clin Psychiatry. 2004;65(5):598–604.PubMedCrossRef
6.
7.
Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89–95.CrossRef
8.
9.••
Sokolowska I, Ngounou Wetie AG, Wormwood K, Thome J, Darie CC, Woods AG. The potential of biomarkers in psychiatry: focus on proteomics. J Neural Transm. 2013 Dec 20. doi:10.​1007/​s00702-013-1134-6. This is a review on the importance to use the proteomics to identify biomarkers for different psychiatric pathologies including ADHD.
10.••
Thome J, Ehlis AC, Fallgatter AJ, Krauel K, Lange KW, Riederer P, et al. Biomarkers for attention-deficit/hyperactivity disorder (ADHD). A consensus report of the WFSBP task force on biological markers and the World Federation of ADHD. World J Biol Psychiatry. 2012;13(5):379–400. This is a comprehensive review on clinical, imaging, genetic and proteomic markers and ADHD. The review concluded that, although some promising candidates such as olfactory sensitivity, substantial echogenicity, no biomarkers for ADHD are available.PubMedCrossRef
11.
12.
Pies R. Beyond reliability: biomarkers and validity in psychiatry. Psychiatry (Edgmont). 2008;5(1):48–52.
13.
Gizer IR, Ficks C, Waldman ID. Candidate gene studies of ADHD: a meta-analytic review. Hum Genet. 2009;126(1):51–90.PubMedCrossRef
14.
Shook D, Brady C, Lee PS, Kenealy L, Murphy ER, Gaillard WD, et al. Effect of dopamine transporter genotype on caudate volume in childhood ADHD and controls. Am J Med Genet B. 2011;156B(1):28–35.CrossRef
15.
Braet W, Johnson KA, Tobin CT, Acheson R, McDonnell C, Hawi Z, et al. fMRI activation during response inhibition and error processing: the role of the DAT1 gene in typically developing adolescents and those diagnosed with ADHD. Neuropsychologia. 2011;49(7):1641–50.PubMedCrossRef
16.•
McGough JJ. Attention deficit hyperactivity disorder pharmacogenetics: the dopamine transporter and D4 receptor. Pharmacogenomics. 2012;13(4):365–8. This is a review on pharmacogenetics and ADHD focusing on DAT1 and DRD4 genes. The author concludes that there is no evidence at present to suggest any role for pharmacogenetics in the clinical management of ADHD for SLA6A3, DRD4 or any other genetic polymorphism.PubMedCrossRef
17.••
Bruxel EM, Akutagava-Martins GC, Salatino-Oliveira A, Contini V, Kieling C, Hutz MH, et al. ADHD pharmacogenetics across the life cycle: new findings and perspectives. Am J Med Genet B Neuropsychiatr Genet. 2014. doi:10.​1002/​ajmg.​b.​32240. This is a systematic review of the literature on ADHD pharmacogenetics to provide a critical discussion of the existent findings, new approaches, limitations, and recommendations for future research. It focuses on the number of studies continues to grow, and the heterogeneity in methodological strategies employed by different studies.PubMed
18.
Durston S, Fossella JA, Mulder MJ, Casey BJ, Ziermans TB, Vessaz MN, et al. Dopamine transporter genotype conveys familial risk of attention-deficit/hyperactivity disorder through striatal activation. J Am Acad Child Adolesc Psychiatry. 2008;47(1):61–7.PubMedCrossRef
19.••
Kambeitz J, Romanos M, Ettinger U. Meta-analysis of the association between dopamine transporter genotype and response to methylphenidate treatment in ADHD. Pharmacogenomics J. 2014;14(1):77–84. This is a a meta-analysis of studies investigating the moderating effect of the SLC6A3 VNTR on response to methylphenidate treatment in subjects with ADHD. The results indicate that SLC6A3 VNTR is not a reliable predictor of methylphenidate treatment success in ADHD.PubMedCrossRef
20.
Bedard AC, Schulz KP, Cook EH, Fan J, Clerkin SM, Ivanov I, et al. Dopamine transporter gene variation modulates activation of striatum in youth with ADHD. Neuroimage. 2010;53(3):935–42.PubMedCrossRefPubMedCentral
21.
Kebir O, Joober R. Neuropsychological endophenotypes in attention-deficit/hyperactivity disorder: a review of genetic association studies. Eur Arch Psychiatry Clin Neurosci. 2011;261(8):583–94.PubMedCrossRef
22.
Barnes JJM, Dean AJ, Nandam LS, O’Connell RG, Bellgrove MA. The molecular genetics of executive function: role of monoamine system genes. Biol Psychiatry. 2011;69(12):E127–43.PubMedCrossRef
23.
Congdon E, Constable RT, Lesch KP, Canli T. Influence of SLC6A3 and COMT variation on neural activation during response inhibition. Biol Psychol. 2009;81(3):144–52.PubMedCrossRefPubMedCentral
24.
Fusar-Poli P, Rubia K, Rossi G, Sartori G, Balottin U. Striatal dopamine transporter alterations in ADHD: pathophysiology or adaptation to psychostimulants? A meta-analysis. Am J Psychiatr. 2012;169(3):264–72.PubMedCrossRef
25.••
Falcone M, Smith RM, Chenoweth MJ, Bhattacharjee AK, Kelsoe JR, Tyndale RF, et al. Neuroimaging in psychiatric pharmacogenetics research: the promise and pitfalls. Neuropsychopharmacology. 2013;38(12):2327–37. This review summarizes progress in efforts to incorporate neuroimaging into genetics and treatment research on major psychiatric disorders, such as schizophrenia, major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, and addiction.PubMedCrossRef
26.
Paloyelis Y, Mehta MA, Faraone SV, Asherson P, Kuntsi J. Striatal sensitivity during reward processing in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2012;51(7):722–32.PubMedCrossRefPubMedCentral
27.
Bellgrove MA, Johnson KA, Barry E, Mulligan A, Hawi Z, Gill M, et al. Dopaminergic haplotype as a predictor of spatial inattention in children with attention-deficit/hyperactivity disorder. Arch Gen Psychiatr. 2009;66(10):1135–42.PubMedCrossRef
28.
Shang CY, Gau SSF. Association between the DAT1 gene and spatial working memory in attention deficit hyperactivity disorder. Int J Neuropsychopharmacol. 2014;17(1):9–21.PubMedCrossRef
29.
Konrad K, Dempfle A, Friedel S, Heiser P, Holtkamp K, Walitza S, et al. Familiality and molecular genetics of attention networks in ADHD. Am J Med Genet B Neuropsychiatr Genet. 2010;153B(1):148–58.PubMed
30.••
Wu J, Xiao HF, Sun HJ, Zou L, Zhu LQ. Role of dopamine receptors in ADHD: a systematic meta-analysis. Mol Neurobiol. 2012;45(3):605–20. This review summarized the ongoing research of DA receptor genes in ADHD pathogenesis and gathered the past published data with meta-analysis and revealed the high risk of DRD5, DRD2, and DRD4 polymorphisms in ADHD.PubMedCrossRef
31.
Taurines R, Grunblatt E, Schecklmann M, Schwenck C, Albantakis L, Reefschlager L, et al. Altered mRNA expression of monoaminergic candidate genes in the blood of children with attention deficit hyperactivity disorder and autism spectrum disorder. World J Biol Psychiatry. 2011;12:104–8.PubMedCrossRef
32.
Shaw P, Eckstrand K, Sharp W, Blumenthal J, Lerch JP, Greenstein D, et al. Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proc Natl Acad Sci U S A. 2007;104(49):19649–54.PubMedCrossRefPubMedCentral
33.••
Wu Z, Yang L, Wang Y. Applying Imaging Genetics to ADHD: the Promises and the Challenges. Mol Neurobiol. 2014 Apr 1. doi:10.​1007/​s12035-014-8683-z. This is an exhaustive review on neuroimaging genetics in ADHD. The authors 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.
34.
Lasky-Su J, Neale BM, Franke B, Anney RJL, Zhou KX, Maller JB, et al. Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations. Am J Med Genet B. 2008;147B(8):1345–54.CrossRef
35.
Winsberg BG, Comings DE. Association of the dopamine transporter gene (DAT1) with poor methylphenidate response. J Am Acad Child Adolesc Psychiatry. 1999;38(12):1474–7.PubMedCrossRef
36.
Manor I, Corbex M, Eisenberg J, Gritsenkso I, Bachner-Melman R, Tyano S, et al. Association of the dopamine D5 receptor with attention deficit hyperactivity disorder (ADHD) and scores on a continuous performance test (TOVA). Am J Med Genet B. 2004;127B(1):73–7.CrossRef
37.
38.
Loo SK, Rich EC, Ishii J, McGough J, McCracken J, Nelson S, et al. Cognitive functioning in affected sibling pairs with ADHD: familial clustering and dopamine genes. J Child Psychol Psychiatry. 2008;49(9):950–7.PubMedCrossRef
39.••
Scassellati C, Bonvicini C, Faraone SV, Gennarelli M. Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses. J Am Acad Child Adolesc Psychiatry. 2012;51(10):1003–19. This is an exhaustive meta-analysis providing evidence for several peripheral biomarkers as being associated with ADHD both in diagnosis and in treatment efficacy.PubMedCrossRef
40.
Park MH, Kim JW, Yang YH, Hong SB, Park S, Kang H, et al. Regional brain perfusion before and after treatment with methylphenidate may be associated with the G1287A polymorphism of the norepinephrine transporter gene in children with attention-deficit/hyperactivity disorder. Neurosci Lett. 2012;514(2):159–63.PubMedCrossRef
41.
Kim BN, Kim JW, Cummins TDR, Bellgrove MA, Hawi Z, Hong SB, et al. Norepinephrine genes predict response time variability and methylphenidate-induced changes in neuropsychological function in attention deficit hyperactivity disorder. J Clin Psychopharmacol. 2013;33(3):356–62.PubMedCrossRef
42.
Bobb AJ, Addington AM, Sidransky E, Gornick MC, Lerch JP, Greenstein DK, et al. Support for association between ADHD and two candidate genes: NET1 and DRD1. Am J Med Genet B. 2005;134B(1):67–72.CrossRef
43.
Kollins SH, Anastopoulos AD, Lachiewicz AM, FitzGerald D, Morrissey-Kane E, Garrett ME, et al. SNPs in dopamine D2 receptor gene (DRD2) and norepinephrine transporter gene (NET) are associated with continuous performance task (CPT) phenotypes in ADHD children and their families. Am J Med Genet B. 2008;147B(8):1580–8.CrossRef
44.
Lesch KP, Selch S, Renner TJ, Jacob C, Nguyen TT, Hahn T, et al. Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: association with neuropeptide Y gene dosage in an extended pedigree. Mol Psychiatry. 2011;16(5):491–503.PubMedCrossRef
45.
Shiffrin ND, Gruber J, Glatt SJ, Faraone SV. No association between MspI allele of the ADRA2A polymorphism and ADHD: meta-analysis of family-based studies. Psychiatr Genet. 2013;23(4):174–5.PubMedCrossRef
46.
Froehlich TE, Epstein JN, Nick TG, Castro MSM, Stein MA, Brinkman WB, et al. Pharmacogenetic predictors of methylphenidate dose-response in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2011;50(11):1129–39.PubMedCrossRefPubMedCentral
47.
Yang L, Qian Q, Liu L, Li H, Faraone SV, Wang Y. Adrenergic neurotransmitter system transporter and receptor genes associated with atomoxetine response in attention-deficit hyperactivity disorder children. J Neural Transm. 2013;120(7):1127–33.PubMedCrossRef
48.••
Sun HJ, Yuan FF, Shen XM, Xiong GL, Wu J. Role of COMT in ADHD: a systematic meta-analysis. Mol Neurobiol. 2014;49(1):251–61. This is a meta-analysis on findings investigating associations between COMT gene and ADHD. The results indicated no association.PubMedCrossRef
49.
Qian QJ, Yang L, Wang YF, Zhang HB, Guan LL, Chen Y, et al. Gene-gene interaction between COMT and MAOA potentially predicts the intelligence of attention-deficit hyperactivity disorder boys in China. Behav Genet. 2010;40(3):357–65.PubMedCrossRef
50.
Thapar A, Langley K, Fowler T, Rice F, Turic D, Whittinger N, et al. Catechol O-methyltransferase gene variant and birth weight predict early-onset antisocial behavior in children with attention-deficit/hyperactivity disorder. Arch Gen Psychiatr. 2005;62(11):1275–8.PubMedCrossRef
51.
Caspi A, Langley K, Milne B, Moffitt TE, O’Donovan M, Owen MJ, et al. A replicated molecular genetic basis for subtyping antisocial behavior in children with attention-deficit/hyperactivity disorder. Arch Gen Psychiatr. 2008;65(2):203–10.PubMedCrossRef
52.
Cheon KA, Jun JY, Cho DY. Association of the catechol-O-methyltransferase polymorphism with methylphenidate response in a classroom setting in children with attention-deficit hyperactivity disorder. Int Clin Psychopharmacol. 2008;23(5):291–8.PubMedCrossRef
53.
Kereszturi E, Tarnok Z, Bognar E, Lakatos K, Farkas L, Gadoros J, et al. Catechol-O-methyltransferase Val158Met polymorphism is associated with methylphenidate response in ADHD children. Am J Med Genet B. 2008;147B(8):1431–5.CrossRef
54.
Manor I, Tyano S, Mel E, Eisenberg J, Bachner-Melman R, Kotler M, et al. Family-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. 2002;7(6):626–32.PubMedCrossRef
55.
Rommelse NNJ, Altink ME, Arias-Vasquez A, Buschgens CJM, Fliers E, Faraone SV, et al. Differential association between MAOA, ADHD and neuropsychological functioning in boys and girls. Am J Med Genet B. 2008;147B(8):1524–30.CrossRef
56.
Nymberg C, Jia T, Lubbe S, Ruggeri B, Desrivieres S, Barker G, et al. Neural mechanisms of attention-deficit/hyperactivity disorder symptoms are stratified by MAOA genotype. Biol Psychiatry. 2013;74(8):607–14.PubMedCrossRef
57.
Kieling C, Genro JP, Hutz MH, Rohde LA. The -1021 C/T DBH polymorphism is associated with neuropsychological performance among children and adolescents with ADHD. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(4):485–90.PubMedCrossRef
58.
Shim SH, Hwangbo Y, Kwon YJ, Jeong HY, Lee BH, Lee HJ, et al. Increased levels of plasma brain-derived neurotrophic factor (BDNF) in children with attention deficit-hyperactivity disorder (ADHD). Prog Neuro-Psychopharmacol Biol Psychiatry. 2008;32(8):1824–8.CrossRef
59.
Kim H, Heo HI, Kim DH, Ko IG, Lee SS, Kim SE, et al. Treadmill exercise and methylphenidate ameliorate symptoms of attention deficit/hyperactivity disorder through enhancing dopamine synthesis and brain-derived neurotrophic factor expression in spontaneous hypertensive rats. Neurosci Lett. 2011;504(1):35–9.PubMedCrossRef
60.
Scassellati C, Zanardini R, Tiberti A, Pezzani M, Valenti V, Effedri P, et al. Serum brain-derived neurotrophic factor (BDNF) levels in attention deficit-hyperactivity disorder (ADHD). Eur Child Adolesc Psichiatry. 2014;23(3):173–7.CrossRef
61.••
Joseph N, Zhang-James Y, Perl A, Faraone SV. Oxidative Stress and ADHD: A Meta-Analysis. J Atten Disord. 2013;20(10):1–10 doi:10.​1177/​1087054713510354​. The authors performed a meta-analysis of studies on oxidative stress and antioxidant status in medication naive patients with ADHD and controls. The results suggest that patients with ADHD have normal levels of antioxidant production, but that their response to oxidative stress is insufficient, leading to oxidative damage.
62.••
Arns M, Conners CK, Kraemer HC. A decade of EEG theta/beta ratio research in ADHD: a meta-analysis. J Atten Disord. 2013;17(5):374–83. This is a meta-analysis on the TBR in ADHD. The results indicated that excessive TBR cannot be considered a reliable diagnostic measure of ADHD, however a substantial sub-group of ADHD patients do deviate on this measure and TBR has prognostic value in this sub-group, warranting its use as a prognostic measure rather than a diagnostic measure.PubMedCrossRef
63.
Yener GG, Basar E. Brain oscillations as biomarkers in neuropsychiatric disorders: following an interactive panel discussion and synopsis. Suppl Clin Neurophysiol. 2013;62:343–63.PubMedCrossRef
64.
Frazier TW, Demaree HA, Youngstrom EA. Meta-analysis of intellectual and neuropsychological test performance in attention-deficit/hyperactivity disorder. Neuropsychology. 2004;18(3):543–55.PubMedCrossRef
65.
Martinussen R, Hayden J, Hogg-Johnson S, Tannock R. A meta-analysis of working memory impairments in children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2005;44(4):377–84.PubMedCrossRef
66.
Willcutt EG, Doyle AE, Nigg JT, Faraone SV, Pennington BF. Validity of the executive function theory of attention-deficit/hyperactivity disorder: a meta-analytic review. Biol Psychiatry. 2005;57(11):1336–46.PubMedCrossRef
67.
Kasper LJ, Alderson RM, Hudec KL. Moderators of working memory deficits in children with attention-deficit/hyperactivity disorder (ADHD): A meta-analytic review. Clin Psychol Rev. 2012;32(7):605–17.PubMedCrossRef
68.
van Ewijk H, Heslenfeld DJ, Luman M, Rommelse NN, Hartman CA, Hoekstra P, et al. Visuospatial working memory in ADHD patients, unaffected siblings, and healthy controls. J Atten Disord. 2014;18(4):369–78.PubMedCrossRef
69.
Cortese S. The neurobiology and genetics of attention-deficit/hyperactivity disorder (ADHD): what every clinician should know. Eur J Paediatr Neurol. 2012;16(5):422–33.PubMedCrossRef
70.
Friedel S, Saar K, Sauer S, Dempfle A, Walitza S, Renner T, et al. Association and linkage of allelic variants of the dopamine transporter gene in ADHD. Mol Psychiatry. 2007;12(10):923–33.PubMedCrossRef
71.
Cheon KA, Ryu YH, Kim JW, Cho DY. The homozygosity for 10-repeat allele at dopamine transporter gene and dopamine transporter density in Korean children with attention deficit hyperactivity disorder: relating to treatment response to methylphenidate. Eur Neuropsychopharmacol. 2005;15(1):95–101.PubMedCrossRef
72.
Franke B, Faraone SV, Asherson P, Buitelaar J, Bau CHD, Ramos-Quiroga JA, et al. The genetics of attention deficit/hyperactivity disorder in adults, a review. Mol Psychiatry. 2012;17(10):960–87.PubMedCrossRefPubMedCentral
73.
Bellgrove MA, Hawi Z, Kirley A, Gill M, Robertson IH. Dissecting the attention deficit hyperactivity disorder (ADHD) phenotype: sustained attention, response variability and spatial attentional asymmetries in relation to dopamine transporter (DAT1) genotype. Neuropsychologia. 2005;43(13):1847–57.PubMedCrossRef
74.
Bellgrove MA, Barry E, Johnson KA, Cox M, Daibhis A, Daly M, et al. Spatial attentional bias as a marker of genetic risk, symptom severity, and stimulant response in ADHD. Neuropsychopharmacology. 2008;33(10):2536–45.PubMedCrossRef
75.
Faraone SV, Spencer TJ, Madras BK, Zhang-James Y, Biederman J. Functional effects of dopamine transporter gene genotypes on in vivo dopamine transporter functioning: a meta-analysis. Mol Psychiatry. 2013;19:880–889.
76.
Noaín D, Avale ME, Wedemeyer C, Calvo D, Peper M, Rubinstein M. Identification of brain neurons expressing the dopamine D4 receptor gene using BAC transgenic mice. Eur J Neurosci. 2006;24(9):2429–38.PubMedCrossRef
77.
Usiello A, Baik JH, Rouge-Pont F, Picetti R, Dierich A, LeMeur M, et al. Distinct functions of the two isoforms of dopamine D2 receptors. Nature. 2000;408(6809):199–203.PubMedCrossRef
78.
Beischlag TV, Marchese A, Meador-Woodruff JH, Damask SP, O’Dowd BF, Tyndale RF, et al. The human dopamine D5 receptor gene: cloning and characterization of the 5′-flanking and promoter region. Biochemistry. 1995;34(17):5960–70.PubMedCrossRef
79.
Li S, Cullen WK, Anwyl R, Rowan MJ. Dopamine-dependent facilitation of LTP induction in hippocampal CA1 by exposure to spatial novelty. Nat Neurosci. 2003;6(5):526–31.PubMed
80.
Stahl SM. Neurotransmission of cognition, part 3. Mechanism of action of selective NRIs: both dopamine and norepinephrine increase in prefrontal cortex. J Clin Psychiatry. 2003;64(3):230–1.PubMedCrossRef
81.
Mick E, Neale B, Middleton FA, McGough JJ, Faraone SV. Genome-wide association study of response to methylphenidate in 187 children with attention-deficit/hyperactivity disorder. Am J Med Genet B. 2008;147B(8):1412–8.CrossRef
82.
Oades RD, Daniels R, Rascher W. Plasma neuropeptide-Y levels, monoamine metabolism, electrolyte excretion and drinking behavior in children with attention-deficit hyperactivity disorder. Psychiatry Res. 1998;80(2):177–86.PubMedCrossRef
83.
Waldman ID, Nigg JT, Gizer IR, Park L, Rappley MD, Friderici K. The adrenergic receptor alpha-2A gene (ADRA2A) and neuropsychological executive functions as putative endophenotypes for childhood ADHD. Cogn Affect Behav Neurosci. 2006;6(1):18–30.PubMedCrossRef
84.
Hong J, Shu-Leong H, Tao X, Lap-Ping Y. Distribution of catechol-O-methyltransferase expression in human central nervous system. Neuroreport. 1998;9(12):2861–4.PubMedCrossRef
85.
Brunner HG, Nelen M, Breakefield XO, Ropers HH, Vanoost BA. Abnormal-behavior associated with a point mutation in the structural gene for monoamine oxidase-A. Science. 1993;262(5133):578–80.PubMedCrossRef
86.
Cases O, Lebrand C, Giros B, Vitalis T, De Maeyer E, Caron MG, et al. Plasma membrane transporters of serotonin, dopamine, and norepinephrine mediate serotonin accumulation in atypical locations in the developing brain of monoamine oxidase A knock-outs. J Neurosci. 1998;18(17):6914–27.PubMed
87.
Deckert J, Catalano M, Syagailo YV, Bosi M, Okladnova O, Di Bella D, et al. Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder. Hum Mol Genet. 1999;8(4):621–4.PubMedCrossRef
88.
Gaspar P, Berger B, Febvret A, Vigny A, Henry JP. Catecholamine innervation of the human cerebral cortex as revealed by comparative immunohistochemistry of tyrosine hydroxylase and dopamine-beta-hydroxylase. J Comp Neurol. 1989;279(2):249–71.PubMedCrossRef
89.
Rogeness GA, Maas JW, Javors MA, Macedo CA, Fischer C, Harris WR. Attention deficit disorder symptoms and urine catecholamines. Psychiatry Res. 1989;27(3):241–51.PubMedCrossRef
90.••
Caylak E. Biochemical and genetic analyses of childhood attention deficit/hyperactivity disorder. Am J Med Genet B. 2012;159B(6):613–27. This is an review on biochemistry and genetics of ADHD. The authors reported many published studies about biochemical abnormalities in ADHD as well as many published genetic studies implicating several genes (dopaminergic: DRD4, DAT1, DRD5, COMT; noradrenergic: DBH, ADRA2A; serotonergic: 5-HTT, HTR1B, HTR2A; cholinergic: CHRNA4, and central nervous system development pathway: SNAP25, BDNF) in the etiology of ADHD.CrossRef
91.
92.
Söllner T, Whiteheart SW, Brunner M, Erdjument-Bromage H, Geromanos S, Tempst P, et al. SNAP receptors implicated in vesicle targeting and fusion. Nature. 1993;362(6418):318–24.PubMedCrossRef
93.
Ghanizadeh A, Berk M. Zinc for treating of children and adolescents with attention-deficit hyperactivity disorder: a systematic review of randomized controlled clinical trials. Eur J Clin Nutr. 2013;67(1):122–4.PubMedCrossRef
94.
Bloch MH, Qawasmi A. Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis. J Am Acad Child Adolesc Psychiatry. 2011;50(10):991–1000.PubMedCrossRefPubMedCentral
95.
Chovanova Z, Muchova J, Sivonova M, Dvorakova M, Zitnanova I, Waczulikova I, et al. Effect of polyphenolic extract, Pycnogenol (R), on the level of 8-oxoguanine in children suffering from attention deficit/hyperactivity disorder. Free Radic Res. 2006;40(9):1003–10.PubMedCrossRef
96.
Dvorakova M, Jezova D, Blazicek P, Trebaticka J, Skodacek I, Suba J, et al. Urinary catecholamines in children with attention deficit hyperactivity disorder (ADHD): Modulation by a polyphenolic extract from pine bark (Pycnogenol((R))). Nutr Neurosci. 2007;10(3–4):151–7.PubMedCrossRef
97.
Garcia RJ, Francis L, Dawood M, Lai ZW, Faraone SV, Perl A. Attention deficit and hyperactivity disorder scores Are elevated and respond to N-acetylcysteine treatment in patients with systemic lupus erythematosus. Arthritis Rheum US. 2013;65(5):1313–8.CrossRef
98.
Snyder SM, Hall JR. A meta-analysis of quantitative EEG power associated with attention-deficit hyperactivity disorder. J Clin Neurophysiol. 2006;23(5):440–55.PubMedCrossRef
99.
Tye C, Rijsdijk F, McLoughlin G. Genetic overlap between ADHD symptoms and EEG theta power. Brain Cogn. 2014;87:168–72.PubMedCrossRef
100.••
Kofler MJ, Rapport MD, Sarver DE, Raiker JS, Orban SA, Friedman LM, et al. Reaction time variability in ADHD: a meta-analytic review of 319 studies. Clin Psychol Rev. 2013;33(6):795–811. This is a meta-analysis of 319 studies of RT variability in children, adolescents, and adults with ADHD relative to typically developing (TD) groups, clinical control groups, and themselves. The results of the meta-analysis indicate that RT variability reflects a stable feature of ADHD and other clinical disorders that is robust to systematic differences across studies.PubMedCrossRef
101.••
Lange KW, Hauser J, Lange KM, Makulska-Gertruda E, Takano T, Takeuchi Y et al. Utility of cognitive neuropsychological assessment in attention-deficit/hyperactivity disorder. Atten Defic Hyperact Disord. 2014 Mar 18. doi:10.​1007/​s12402-014-0132-3. This is an interesting review on the utility of neuropsychological tests in ADHD. The authors concluded that cognitive neuropsychological assessment appears to be at present of limited clinical use and confined to individual descriptions.
102.••
Kasparek T, Theiner P, Filova A. Neurobiology of ADHD from childhood to adulthood: findings of imaging methods. J Atten Disord. 2013;20(10):1–13. doi:10.​1177/​1087054713505322​. The authors concluded that changes in neuronal plasticity may be behind persisting brain changes in ADHD. Current treatment approaches seem to improve these neuroplastic processes, and, therefore, may have a positive effect on the neuropathology of ADHD.
103.
Bellgrove MA, Mattingley JB, Hawi Z, Mullins C, Kirley A, Gill M, et al. Impaired temporal resolution of visual attention and dopamine beta hydroxylase genotype in attention-deficit/hyperactivity disorder. Biol Psychiatry. 2006;60(10):1039–45.
104.
Wasserman T, Wasserman LD. The sensitivity and specificity of neuropsychological tests in the diagnosis of attention deficit hyperactivity disorder. Appl Neuropsychol Child. 2012;1(2):90–9.
Metadata
Title
Biomarkers in the Diagnosis of ADHD – Promising Directions
Authors
Stephen V. Faraone
Cristian Bonvicini
Catia Scassellati
Publication date
01-11-2014
Publisher
Springer US
Published in
Current Psychiatry Reports / Issue 11/2014
Print ISSN: 1523-3812
Electronic ISSN: 1535-1645
DOI
https://doi.org/10.1007/s11920-014-0497-1

Other articles of this Issue 11/2014

Current Psychiatry Reports 11/2014 Go to the issue

Autism Spectrum Disorders (ES Brodkin, Section Editor)

Multimodal Imaging in Autism: an Early Review of Comprehensive Neural Circuit Characterization

Sleep Disorders (P Gehrman, Section Editor)

The Interplay Between Sleep and Emotion Regulation: Conceptual Framework Empirical Evidence and Future Directions

Substance Use and Related Disorders (F Levin and E Dakwar, Section Editors)

At the Crossroads: The Intersection of Substance Use Disorders, Anxiety Disorders, and Posttraumatic Stress Disorder

Genetic Disorders (W Berrettini, Section Editor)

Genetics of Opiate Addiction

Complex Medical-Psychiatric Issues (MB Riba, Section Editor)

Collaborative Care: Models for Treatment of Patients with Complex Medical-Psychiatric Conditions

Psychiatry in the Digital Age (JS Luo, Section Editor)

Privacy in the Digital World: Medical and Health Data Outside of HIPAA Protections