Pharmacology and genetics of autism: Implications for diagnosis and treatment

Personalized Medicine

Volumn 5, Issue 6, 2008, Pages 599-607

  Brkanac, Zoran ^a   Raskind, Wendy H ^a,b   King, Bryan H ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

Autism; Disease modifying treatments; Fragile X; Genetics; Molecular pathways; Rett syndrome

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; CONTACTIN ASSOCIATED PROTEIN-LIKE 2; CYCLIN DEPENDENT LIKE KINASE 5; FORKHEAD BOX G1B; FORKHEAD TRANSCRIPTION FACTOR; FRAGILE X MENTAL RETARDATION PROTEIN; GENE PRODUCT; METABOTROPIC RECEPTOR 5; METHYL CPG BINDING PROTEIN 2; NEUREXIN; NEUROLIGIN; NEUROLIGIN 3; NEUROLIGIN 4; P21 ACTIVATED KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN SHANK3; UNCLASSIFIED DRUG;

AUTISM; BRAIN DEVELOPMENT; CHROMOSOME DELETION; CHROMOSOME STRUCTURE; COMPUTER SIMULATION; EFFECT SIZE; ENZYME ACTIVITY; FRAGILE X SYNDROME; GENE DELETION; GENE FUNCTION; GENE LOCATION; GENE LOCUS; GENE MUTATION; GENE REPLICATION; GENE SEQUENCE; GENETIC LINKAGE; GENETIC SCREENING; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HUMAN; INCIDENCE; NERVE EXCITABILITY; NONHUMAN; PHARMACOGENOMICS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; RETT SYNDROME; REVIEW;

EID: 57749207233     PISSN: 17410541     EISSN: 1744828X     Source Type: Journal    
DOI: 10.2217/17410541.5.6.599     Document Type: Review

References (82)

1. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Press, Washington DC, USA (1994)
2. Lord C, Rutter M, Le Couteur A: Autism Diagnostic Interview - Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J. Autism Dev. Disord. 24, 659-685 (1994).
3. Lord C, Risi S, Lambrecht L et al.: The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J. Autism Dev. Disord. 30, 205-223 (2000).
4. Fombonne E: Epidemiological studies of pervasive developmental disorders. In: Handbook of Autism and Pervasive Developmental Disorders. Volkmar F, Paul R, Klin A, Cohen D (Eds). Wiley, Hoboken, NJ, USA, 42-69 (2005).
5. King BH, Bostic JQ: An update on pharmacologic treatments for autism spectrum disorders. Child Adolesc. Psychiatr. Clin. N. Am. 15, 161-175 (2006).
6. McCracken JT, McGough J, Shah B et al.: Risperidone in children with autism and serious behavioral problems. N. Engl. J. Med. 347, 314-321 (2002).
7. Aman MG, Hollway JA, McDougle CJ et al.: Cognitive effects of risperidone in children with autism and irritable behavior. J. Child Adolesc. Psychopharmacol. 18, 227-236 (2008).
8. Aman MG, Arnold LE, Ramadan Y et al.: Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity. Arch. Gen. Psychiatry 62, 1266-1274 (2005).
9. Posey DJ, Aman MG, McCracken JT et al.: Positive effects of methylphenidate on inattention and hyperactivity in pervasive developmental disorders: an analysis of secondary measures. Biol. Psychiatry 61, 538-544 (2007).
10. Rogers SJ, Vismara LA: Evidence-based comprehensive treatments for early autism. J. Clin. Child Adolesc. Psychol. 37, 8-38 (2008).
11. Parikh MS, Kolevzon A, Hollander E: Psychopharmacology of aggression in children and adolescents with autism: a critical review of efficacy and tolerability. J. Child Adolesc. Psychopharmacol. 18, 157-178 (2008).
12. Bailey A, Le Couteur A, Gottesman I et al.: Autism as a strongly genetic disorder: evidence from a British twin study. Psychol. Med. 25, 63-77 (1995).
13. Folstein S, Rutter M: Infantile autism: a genetic study of 21 twin pairs. J. Child Psychol. Psychiatry 18, 297-321 (1977).
14. Steffenburg S, Gillberg C, Hellgren L et al.: A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J. Child Psychol. Psychiatry 30, 405-416 (1989).
15. Pritchard J, Cox N: The allelic architecture of human disease genes: common disease - common variant... or not? Hum. Mol. Genet. 11, 2417-2423 (2002).
16. Pritchard JK: Are rare variants responsible for susceptibility to complex diseases? Am. J. Hum. Genet. 69, 124-137 (2001).
17. Pickles A, Bolton P, Macdonald H et al.: Latent-class analysis of recurrence risks for complex phenotypes with selection and measurement error: a twin and family history study of autism. Am. J. Hum. Genet. 57, 717-726 (1995).
18. Risch N, Spiker D, Lotspeich L et al.: A genomic screen of autism: evidence for a multilocus etiology. Am. J. Hum. Genet. 65, 493-507 (1999).
19. Yang MS, Gill M: A review of gene linkage, association and expression studies in autism and an assessment of convergent evidence. Int. J. Dev. Neurosci. 25, 69-85 (2007).
20. Gupta AR, State MW: Recent advances in the genetics of autism. Biol. Psychiatry 61, 429-437 (2007).
21. Veenstra-Vanderweele J, Cook EH Jr: Molecular genetics of autism spectrum disorder. Mol. Psychiatry 9, 819-832 (2004).
22. Freitag CM: The genetics of autistic disorders and its clinical relevance: a review of the literature. Mol. Psychiatry 12, 2-22 (2007).
23. Morrow AM, Yoo YS, Flavell SW et al.: Identifying autism loci and genes by tracing recent shared ancestry. Science 321, 218-223 (2008).
24. Vorstman JA, Staal WG, van Daalen E, van Engeland H, Hochstenbach PF, Franke L: Identification of novel autism candidate regions through analysis of reported cytogenetic abnormalities associated with autism. Mol. Psychiatry 11, 18-28 (2006).
25. Szatmari P, Paterson AD, Zwaigenbaum L et al.: Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat. Genet. 39, 319-328 (2007).
26. Sebat J, Lakshmi B, Malhotra D et al.: Strong association of de novo copy number mutations with autism. Science 316, 445-449 (2007).
27. Kumar RA, KaraMohamed S, Sudi J et al.: Recurrent 16p11.2 microdeletions in autism. Hum. Mol. Genet. 17, 628-638 (2008).
28. Christian SL, Brune CW, Sudi J et al.: Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder. Biol. Psychiatry 63(12), 1111-1117 (2008).
29. Weiss LA, Shen Y, Korn JM et al.: Association between microdeletion and microduplication at 16p11.2 and autism. N. Engl. J. Med. 358, 667-675 (2008).
30. Marshall CR, Noor A, Vincent JB et al.: Structural variation of chromosomes in autism spectrum disorder. Am. J. Hum. Genet. 82, 477-488 (2008).
31. Thomas NS, Sharp AJ, Browne CE, Skuse D, Hardie C, Dennis NR: Xp deletions associated with autism in three females. Hum. Genet. 104, 43-48 (1999).
32. Jamain S, Quach H, Betancur C et al.: Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat. Genet. 34, 27-29 (2003).
33. Laumonnier F, Bonnet-Brilhault F, Gomot M et al.: X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am. J. Hum. Genet. 74, 552-557 (2004).
34. Yan J, Oliveira G, Coutinho A et al.: Analysis of the neuroligin 3 and 4 genes in autism and other neuropsychiatric patients. Mol. Psychiatry 10, 329-332 (2005).
35. Lawson-Yuen A, Saldivar JS, Sommer S, Picker J: Familial deletion within NLGN4 associated with autism and Tourette syndrome. Eur. J. Hum. Genet. 16, 614-618 (2008).
36. Yan J, Feng J, Schroer R et al.: Analysis of the neuroligin 4Y gene in patients with autism. Psychiatr. Genet. 18, 204-207 (2008).
37. Kim HG, Kishikawa S, Higgins AW et al.: Disruption of neurexin 1 associated with autism spectrum disorder. Am. J. Hum. Genet. 82, 199-207 (2008).
38. Feng J, Schroer R, Yan J et al.: High frequency of neurexin 1β signal peptide structural variants in patients with autism. Neurosci. Lett. 409, 10-13 (2006).
39. Moessner R, Marshall CR, Sutcliffe JS et al.: Contribution of SHANK3 mutations to autism spectrum disorder. Am. J. Hum. Genet. 81, 1289-1297 (2007).
40. Durand CM, Betancur C, Boeckers TM et al.: Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat. Genet. 39, 25-27 (2007).
41. Buxbaum JD, Cai G, Chaste P et al.: Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly. Am. J. Med. Genet. B Neuropsychiatr. Genet. 144, 484-491 (2007).
42. Herman GE, Henninger N, Ratliff-Schaub K, Pastore M, Fitzgerald S, McBride KL: Genetic testing in autism: how much is enough? Genet. Med. 9, 268-274 (2007).
43. Herman GE, Butter E, Eurile B, Pastore M, Prior TW, Sommer A: Increasing knowledge of PTEN germline mutations: two additional patients with autism and macrocephaly. Am. J. Med. Genet. A. 143, 589-593 (2007).
44. Butler MG, Dasouki MJ, Zhou XP et al.: Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations. J. Med. Genet. 42, 318-321 (2005).
45. Strauss KA, Puffenberger EG, Huentelman MJ et al.: Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2. N. Engl. J. Med. 354, 1370-1377 (2006).
46. Alarcon M, Abrahams BS, Stone JL et al.: Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene. Am. J. Hum. Genet. 82, 150-159 (2008).
47. Arking DE, Cutler DJ, Brune CW et al.: A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism. Am. J. Hum. Genet. 82, 160-164 (2008).
48. Bakkaloglu B, O'Roak BJ, Louvi A et al.: Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders. Am. J. Hum. Genet. 82, 165-173 (2008).
49. Hagerman RJ: Lessons from fragile X regarding neurobiology, autism, and neurodegeneration. J. Dev. Behav. Pediatr. 27, 63-74 (2006).
50. Cohen D, Pichard N, Tordjman S et al.: Specific genetic disorders and autism: clinical contribution towards their identification. J. Autism Dev. Disord. 35, 103-116 (2005).
51. Reiss AL, Hall SS: Fragile X syndrome: assessment and treatment implications. Child Adolesc. Psychiatr. Clin. N. Am. 16, 663-675 (2007).
52. Verkerk AJ, Pieretti M, Sutcliffe JS et al.: Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65, 905-914 (1991).
53. Hammond LS, Macias MM, Tarleton JC, Shashidhar Pai G: Fragile X syndrome and deletions in FMR1: new case and review of the literature. Am. J. Med. Genet. 72, 430-434 (1997).
54. Bear MF, Huber KM, Warren ST: The mGluR theory of fragile X mental retardation. Trends Neurosci. 27, 370-377 (2004).
55. Dolen G, Osterweil E, Rao BS et al.: Correction of fragile X syndrome in mice. Neuron 56, 955-962 (2007).
56. Hayashi ML, Rao BS, Seo JS et al.: Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice. Proc. Natl Acad. Sci. USA 104, 11489-11494 (2007).
57. Bittel DC, Kibiryeva N, Butler MG: Whole genome microarray analysis of gene expression in subjects with fragile X syndrome. Genet. Med. 9, 464-472 (2007).
58. McBride SM, Choi CH, Wang Y et al.: Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome. Neuron 45, 753-764 (2005).
59. Yan QJ, Rammal M, Tranfaglia M, Bauchwitz RP: Suppression of two major fragile X syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology 49, 1053-1066 (2005).
60. D'Hulst C, Kooy RF: The GABAA receptor: a novel target for treatment of fragile X? Trends Neurosci. 30, 425-431 (2007).
61. Li J, Pelletier MR, Perez Velazquez JL, Carlen PL: Reduced cortical synaptic plasticity and GluR1 expression associated with fragile X mental retardation protein deficiency. Mol. Cell Neurosci. 19, 138-151 (2002).
62. Hessl D, Glaser B, Dyer-Friedman J et al.: Cortisol and behavior in fragile X syndrome. Psychoneuroendocrinology 27, 855-872 (2002).
63. Amir RE, van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY: Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 23, 185-188 (1999).
64. Erlandson A, Hagberg B: MECP2 abnormality phenotypes: clinicopathologic area with broad variability. J. Child Neurol. 20, 727-732 (2005).
65. Villard L: MECP2 mutations in males. J. Med. Genet. 44, 417-423 (2007).
66. van Esch H, Bauters M, Ignatius J et al.: Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males. Am. J. Hum. Genet. 77, 442-453 (2005).
67. del Gaudio D, Fang P, Scaglia F et al.: Increased MECP2 gene copy number as the result of genomic duplication in neurodevelopmentally delayed males. Genet. Med. 8, 784-792 (2006).
68. Mari F, Azimonti S, Bertani I et al.: CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome. Hum. Mol. Genet. 14, 1935-1946 (2005).
69. Scala E, Ariani F, Mari F et al.: CDKL5/STK9 is mutated in Rett syndrome variant with infantile spasms. J. Med. Genet. 42, 103-107 (2005).
70. Weaving LS, Christodoulou J, Williamson SL et al.: Mutations of CDKL5 cause a severe neurodevelopmental disorder with infantile spasms and mental retardation. Am. J. Hum. Genet. 75, 1079-1093 (2004).
71. Ariani F, Hayek G, Rondinella D et al.: FOXG1 is responsible for the congenital variant of Rett syndrome. Am. J. Hum. Genet. 83, 89-93 (2008).
72. Philippe C, Villard L, De Roux N et al.: Spectrum and distribution of MECP2 mutations in 424 Rett syndrome patients: a molecular update. Eur J. Med. Genet. 49, 9-18 (2006).
73. Ben Zeev Ghidon B: Rett syndrome. Child Adolesc. Psychiatr. Clin. N. Am. 16, 723-743 (2007).
74. Coutinho AM, Oliveira G, Katz C et al.: MECP2 coding sequence and 3′UTR variation in 172 unrelated autistic patients. Am. J. Med. Genet. B Neuropsychiatr. Genet. 144B, 475-483 (2007).
75. Francke U: Mechanisms of disease: neurogenetics of MeCP2 deficiency. Nat. Clin. Pract. Neurol. 2, 212-221 (2006).
76. Guy J, Gan J, Selfridge J, Cobb S, Bird A: Reversal of neurological defects in a mouse model of Rett syndrome. Science 315, 1143-1147 (2007).
77. Giacometti E, Luikenhuis S, Beard C, Jaenisch R: Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2. Proc. Natl Acad. Sci. USA 104, 1931-1936 (2007).
78. Chang Q, Khare G, Dani V, Nelson S, Jaenisch R: The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron 49, 341-348 (2006).
79. Varoqueaux F, Aramuni G, Rawson RL et al.: Neuroligins determine synapse maturation and function. Neuron 51, 741-754 (2006).
80. Graf ER, Zhang X, Jin SX, Linhoff MW, Craig AM: Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins. Cell 119, 1013-1026 (2004).
81. Meyer G, Varoqueaux F, Neeb A, Oschlies M, Brose N: The complexity of PDZ domain-mediated interactions at glutamatergic synapses: a case study on neuroligin. Neuropharmacology 47, 724-733 (2004).
82. McCabe LL, McCabe ER: Expanded newborn screening: implications for genomic medicine. Annu. Rev. Med. 59, 163-175 (2008).