Fragile X: Leading the way for targeted treatments in autism

Neurotherapeutics

Volumn 7, Issue 3, 2010, Pages 264-274

  Wang, Lulu W ^a,b   Berry Kravis, Elizabeth ^c   Hagerman, Randi J ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c RUSH UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Animal model; ASD; Autism; Fragile X syndrome; GABA; MGluR; Treatment

Indexed keywords

2 METHYL 6 (PHENYLETHYNYL)PYRIDINE; 4 AMINOBUTYRIC ACID RECEPTOR STIMULATING AGENT; 6 QUINOXALINECARBOXYLIC ACID PIPERIDIDE; AFQ 056; ARBACLOFEN; ARIPIPRAZOLE; BACLOFEN; FENOBAM; FRAGILE X MENTAL RETARDATION PROTEIN; GELATINASE B; IMIDAZOLE DERIVATIVE; LITHIUM; MESSENGER RNA; METABOTROPIC RECEPTOR 1; METABOTROPIC RECEPTOR 5; METABOTROPIC RECEPTOR ANTAGONIST; MINOCYCLINE; RISPERIDONE; RO 4917523; STX 107; UNCLASSIFIED DRUG;

APPETITE; ARTICLE; AUTISM; BODY WEIGHT; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; DRUG TARGETING; DRUG TOLERABILITY; FATIGUE; FMR 1 GENE; FRAGILE X SYNDROME; GENE; GENE MUTATION; HUMAN; NONHUMAN; OFF LABEL DRUG USE; PATHOPHYSIOLOGY; PHENOTYPE; PRIORITY JOURNAL; PROTEIN FUNCTION; SIDE EFFECT; SINGLE DRUG DOSE; TREATMENT RESPONSE; ANIMAL; AUTISTIC DISORDER; GENETICS;

ANIMALS; AUTISTIC DISORDER; FRAGILE X SYNDROME; HUMANS;

EID: 77954915376     PISSN: 19337213     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.nurt.2010.05.005     Document Type: Article

References (145)

1. Hagerman R.J., Rivera S.M., Hagerman P.J. The fragile X family of disorders: a model for autism and targeted treatments. Curr Pediatr Rev 2008, 4:40-52.
2. Reddy K.S. Cytogenetic abnormalities and fragile-X syndrome in autism spectrum disorder. BMC Med Genet 2005, 6:3.
3. van Karnebeek C.D., Jansweijer M.C., Leenders A.G., Offringa M., Hennekam R.C. Diagnostic investigations in individuals with mental retardation: a systematic literature review of their usefulness. Eur J Hum Genet 2005, 13:6-25.
4. Fernandez-Carvajal I., Walichiewicz P., Xiaosen X., Pan R., Hagerman P.J., Tassone F. Screening for expanded alleles of the FMR1 gene in blood spots from newborn males in a Spanish population. J Mol Diagn 2009, 11:324-329.
5. Hagerman P.J. The fragile X prevalence paradox [Erratum in: J Med Genet 2008;45:768]. J Med Genet 2008, 45:498-499.
6. Dombrowski C., Lévesque S., Morel M.L., Rouillard P., Morgan K., Rousseau F. Premutation and intermediate-size FMR1 alleles in 10 572 males from the general population: loss of an AGG interruption is a late event in the generation of fragile X syndrome alleles. Hum Mol Genet 2002, 11:371-378.
7. Verkerk A.J., Pieretti M., Sutcliffe J.S., 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 1991, 65:905-914.
8. Qin M., Kang J., Burlin T.V., Jiang C., Smith C.B. Postadolescent changes in regional cerebral protein synthesis: an in vivo study in the FMR1 null mouse. J Neurosci 2005, 25:5087-5095.
9. Bassell G.J., Warren S.T. Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function. Neuron 2008, 60:201-214.
10. Tassone F., Hagerman R.J., Iklé D.N., et al. FMRP expression as a potential prognostic indicator in fragile X syndrome. Am J Med Genet 1999, 84:250-261.
11. Loesch D.Z., Huggins R.M., Hagerman R.J. Phenotypic variation and FMRP levels in fragile X. Ment Retard Dev Disabil Res Rev 2004, 10:31-41.
12. Rogers S.J., Wehner D.E., Hagerman R. The behavioral phenotype in fragile X: symptoms of autism in very young children with fragile X syndrome, idiopathic autism, and other developmental disorders. J Dev Behav Pediatr 2001, 22:409-417.
13. Kaufmann W.E., Cortell R., Kau A.S., et al. Autism spectrum disorder in fragile X syndrome: communication, social interaction, and specific behaviors. Am J Med Genet 2004, 129A:225-234.
14. Loesch D.Z., Bui Q.M., Dissanayake C., et al. Molecular and cognitive predictors of the continuum of autistic behaviours in fragile X. Neurosci Biobehav Rev 2007, 31:315-326.
15. Garcia-Nonell C., Ratera E.R., Harris S., et al. Secondary medical diagnosis in fragile X syndrome with and without autism spectrum disorder. Am J Med Genet A 2008, 146A:1911-1916.
16. de Vries B.B., Wiegers A.M., Smits A.P., et al. Mental status of females with an FMR1 gene full mutation. Am J Hum Genet 1996, 58:1025-1032.
17. Bennetto L., Pennington B.F. Neuropsychology. Fragile X syndrome: diagnosis, treatment, and research 2002, 206-248. Johns Hopkins University Press, Baltimore. 3rd ed. R.J. Hagerman, P.J. Hagerman (Eds.).
18. Hagerman R.J. Physical and behavioral phenotype. Fragile X syndrome: diagnosis, treatment, and research 2002, 3-109. Johns Hopkins University Press, Baltimore. 3rd ed. R.J. Hagerman, P.J. Hagerman (Eds.).
19. Cronister A., Schreiner R., Wittenberger M., Amiri K., Harris K., Hagerman R.J. Heterozygous fragile X female: historical, physical, cognitive, and cytogenetic features. Am J Med Genet 1991, 38:269-274.
20. Sullivan A.K., Marcus M., Epstein M.P., et al. Association of FMR1 repeat size with ovarian dysfunction. Hum Reprod 2005, 20:402-412.
21. Wittenberger M.D., Hagerman R.J., Sherman S.L., et al. The FMR1 premutation and reproduction. Fertil Steril 2007, 87:456-465.
22. Tassone F., Hagerman R.J., Taylor A.K., Gane L.W., Godfrey T.E., Hagerman P.J. Elevated levels of FMR1 mRNA in carrier males: a new mechanism of involvement in the fragile-X syndrome. Am J Hum Genet 2000, 66:6-15.
23. Hagerman R.J. Fragile X Syndrome. Management of genetic syndromes 2010, 397-411. Wiley & Sons, New York. 3rd ed. S.B. Cassidy, J.E. Allanson (Eds.).
24. Jacquemont S., Hagerman R.J., Leehey M.A., et al. Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population. JAMA 2004, 291:460-469.
25. Hagerman R.J., Leavitt B.R., Farzin F., et al. Fragile-X-associated tremor/ataxia syndrome (FXTAS) in females with the FMR1 premutation. Am J Hum Genet 2004, 74:1051-1056.
26. Coffey S.M., Cook K., Tartaglia N., et al. Expanded clinical phenotype of women with the FMR1 premutation. Am J Med Genet A 2008, 146A:1009-1016.
27. Rodriguez-Revenga L., Madrigal I., Alegret M., Santos M., Milà M. Evidence of depressive symptoms in fragile-X syndrome premutated females. Psychiatr Genet 2008, 18:153-155.
28. Arocena D.G., Iwahashi C.K., Won N., et al. Induction of inclusion formation and disruption of lamin A/C structure by premutation CGG-repeat RNA in human cultured neural cells. Hum Mol Genet 2005, 14:3661-3671.
29. Garcia-Arocena D., Yang J.E., Brouwer J.R., et al. Fibroblast phenotype in male carriers of FMR1 premutation alleles. Hum Mol Genet 2010, 19:299-312.
30. Adams J.S., Adams P.E., Nguyen D., et al. Volumetric brain changes in females with fragile X-associated tremor/ataxia syndrome (FXTAS). Neurology 2007, 69:851-859.
31. Greco C.M., Berman R.F., Martin R.M., et al. Neuropathology of fragile X-associated tremor/ataxia syndrome (FXTAS). Brain 2006, 129:243-255.
32. Greco C.M., Soontrapornchai K., Wirojanan J., Gould J.E., Hagerman P.J., Hagerman R.J. Testicular and pituitary inclusion formation in fragile X associated tremor/ataxia syndrome. J Urol 2007, 177:1434-1437.
33. Gokden M., Al-Hinti J.T., Harik S.I. Peripheral nervous system pathology in fragile X tremor/ataxia syndrome (FXTAS). Neuropathology 2009, 29:280-284.
34. Chen Y., Tassone F., Berman R.F., et al. Murine hippocampal neurons expressing Fmr1 gene premutations show early developmental deficits and late degeneration. Hum Mol Genet 2010, 19:196-208.
35. Farzin F., Perry H., Hessl D., et al. Autism spectrum disorders and attention-deficit/hyperactivity disorder in boys with the fragile X premutation. J Dev Behav Pediatr 2006, 27(2 Suppl):S137-S144.
36. Aziz M., Stathopulu E., Callias M., et al. Clinical features of boys with fragile X premutations and intermediate alleles. Am J Med Genet B Neuropsychiatr Genet 2003, 121B:119-127.
37. Bailey D.B., Raspa M., Olmsted M., Holiday D.B. Co-occurring conditions associated with FMR1 gene variations: findings from a national parent survey. Am J Med Genet A 2008, 146A:2060-2069.
38. Hunter J.E., Allen E.G., Abramowitz A., et al. No evidence for a difference in neuropsychological profile among carriers and noncarriers of the FMR1 premutation in adults under the age of 50. Am J Hum Genet 2008, 83:692-702.
39. Grigsby J., Brega A.G., Engle K., et al. Cognitive profile of fragile X premutation carriers with and without fragile X-associated tremor/ataxia syndrome. Neuropsychology 2008, 22:48-60.
40. Cornish K.M., Kogan C.S., Li L., Turk J., Jacquemont S., Hagerman R.J. Lifespan changes in working memory in fragile X premutation males. Brain Cogn 2009, 69:551-558.
41. Moore C.J., Daly E.M., Schmitz N., et al. A neuropsychological investigation of male premutation carriers of fragile X syndrome. Neuropsychologia 2004, 42:1934-1947.
42. Clifford S., Dissanayake C., Bui Q.M., Huggins R., Taylor A.K., Loesch D.Z. Autism spectrum phenotype in males and females with fragile X full mutation and premutation. J Autism Dev Disord 2007, 37:738-747.
43. Bourgeois J, Seritan A, Casillas E, et al. Lifetime prevalence of mood and anxiety disorders in fragile X premutation carriers. J Clin Psychiatry (in press).
44. Roberts J.E., Bailey D.B., Mankowski J., et al. Mood and anxiety disorders in females with the FMR1 premutation. Am J Med Genet B Neuropsychiatr Genet 2009, 150B:130-139.
45. Bourgeois J.A., Coffey S.M., Rivera S.M., et al. A review of fragile X premutation disorders: expanding the psychiatric perspective. J Clin Psychiatry 2009, 70:852-862.
46. Brouwer J.R., Severijnen E., de Jong F.H., et al. Altered hypothalamus-pituitary-adrenal gland axis regulation in the expanded CGG-repeat mouse model for fragile X-associated tremor/ataxia syndrome. Psychoneuroendocrinology 2008, 33:863-873.
47. Adams P.E., Adams J.S., Nguyen D.V., et al. Psychological symptoms correlate with reduced hippocampal volume in fragile X premutation carriers. Am J Med Genet B Neuropsychiatr Genet 2010, 153B(3):775-785.
48. Miller L.J., McIntosh D.N., McGrath J., et al. Electrodermal responses to sensory stimuli in individuals with fragile X syndrome: a preliminary report. Am J Med Genet 1999, 83:268-279.
49. 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 1994, 24:659-685.
50. Lord C., Rutter M., DiLavore P.C., Risi S. Autism Diagnostic Observation Schedule 1999, Western Psychological Services, Los Angeles, CA.
51. Harris S.W., Hessl D., Goodlin-Jones B., et al. Autism profiles of males with fragile X syndrome. Am J Ment Retard 2008, 113:427-438.
52. Hagerman R.J., Jackson A.W., Levitas A., Rimland B., Braden M. An analysis of autism in fifty males with the fragile X syndrome. Am J Med Genet A 1986, 23:359-374.
53. Bailey D.B., Mesibov G.B., Hatton D.D., Clark R.D., Roberts J.E., Mayhew L. Autistic behavior in young boys with fragile X syndrome. J Autism Dev Disord 1998, 28:499-508.
54. Baumgardner T.L., Reiss A.L., Freund L.S., Abrams M.T. Specification of the neurobehavioral phenotype in males with fragile X syndrome. Pediatrics 1995, 95:744-752.
55. Kerby D.S., Dawson B.L. Autistic features, personality, and adaptive behavior in males with the fragile X syndrome and no autism. Am J Ment Retard 1994, 98:455-462.
56. Merenstein S.A., Sobesky W.E., Taylor A.K., Riddle J.E., Tran H.X., Hagerman R.J. Molecular-clinical correlations in males with an expanded FMR1 mutation. Am J Med Genet 1996, 64:388-394.
57. Hall S.S., Lightbody A.A., Reiss A.L. Compulsive, self-injurious, and autistic behavior in children and adolescents with fragile X syndrome. Am J Ment Retard 2008, 113:44-53.
58. Bailey A., Bolton P., Butler L., et al. Prevalence of the fragile X anomaly amongst autistic twins and singletons. J Child Psychol Psychiatry 1993, 34:673-688.
59. Bailey A., Phillips W., Rutter M. Autism: towards an integration of clinical, genetic, neuropsychological, and neurobiological perspectives. J Child Psychol Psychiatry 1996, 37:89-126.
60. Dykens E.M., Volkmar F.R. Medical conditions associated with autism. Handbook of autism and pervasive developmental disorders 1997, 388-410. John Wiley & Sons, New York. 2nd ed. D.J. Cohen, F.R. Volkmar (Eds.).
61. Nowicki S.T., Tassone F., Ono M.Y., et al. The Prader-Willi phenotype of fragile X syndrome. J Dev Behav Pediatr 2007, 28:133-138.
62. Roberts J., Price J., Barnes E., et al. Receptive vocabulary, expressive vocabulary, and speech production of boys with fragile X syndrome in comparison to boys with Down syndrome. Am J Ment Retard 2007, 112:177-193.
63. Kau A.S., Tierney E., Bukelis I., et al. Social behavior profile in young males with fragile X syndrome: characteristics and specificity. Am J Med Genet 2004, 126A:9-17.
64. Hatton D.D., Sideris J., Skinner M., et al. Autistic behavior in children with fragile X syndrome: prevalence, stability, and the impact of FMRP. Am J Med Genet A 2006, 140A:1804-1813.
65. Lewis P., Abbeduto L., Murphy M., et al. Cognitive, language and social-cognitive skills of individuals with fragile X syndrome with and without autism. J Intellect Disabil Res 2006, 50:532-545.
66. Chiu S., Wegelin J.A., Blank J., et al. Early acceleration of head circumference in children with fragile X syndrome and autism. J Dev Behav Pediatr 2007, 28:31-35.
67. Courchesne E., Carper R., Akshoomoff N. Evidence of brain overgrowth in the first year of life in autism. JAMA 2003, 290:337-344.
68. Butler M.G., Dasouki M.J., Zhou X.P., et al. Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations. J Med Genet 2005, 42:318-321.
69. Reiss A.L., Freund L., Tseng J.E., Joshi P.K. Neuroanatomy in fragile X females: the posterior fossa. Am J Hum Genet 1991, 49:279-288.
70. Mostofsky S.H., Mazzocco M.M., Aakalu G., Warsofsky I.S., Denckla M.B., Reiss A.L. Decreased cerebellar posterior vermis size in fragile X syndrome: correlation with neurocognitive performance. Neurology 1998, 50:121-130.
71. Murakami J.W., Courchesne E., Press G.A., Yeung-Courchesne R., Hesselink J.R. Reduced cerebellar hemisphere size and its relationship to vermal hypoplasia in autism. Arch Neurol 1989, 46:689-694.
72. Ciesielski K.T., Harris R.J., Hart B.L., Pabst H.F. Cerebellar hypoplasia and frontal lobe cognitive deficits in disorders of early childhood. Neuropsychologia 1997, 35:643-655.
73. Pierce K., Courchesne E. Evidence for a cerebellar role in reduced exploration and stereotyped behavior in autism. Biol Psychiatry 2001, 49:655-664.
74. Mazzocco M.M., Kates W.R., Baumgardner T.L., Freund L.S., Reiss A.L. Autistic behaviors among girls with fragile X syndrome. J Autism Dev Disord 1997, 27:415-435.
75. Van Essen D.C., Maunsell H.H. Hierarchical organization of the functional streams in the visual cortex. Trends Neurosci 1983, 6:370-375.
76. Sagi D., Julesz B. "Where" and "what" in vision. Science 1985, 228:1217-1219.
77. Kogan C.S., Boutet I., Cornish K.M., et al. Differential impact of the FMR1 gene on visual processing in fragile X syndrome. Brain 2004, 127:591-601.
78. Spencer J., O'Brien J., Riggs K., Braddick O., Atkinson J., Wattam-Bell J. Motion processing in autism: evidence for a dorsal stream deficiency. Neuroreport 2000, 11:2765-2767.
79. Bertone A., Mottron L., Jelenic P., Faubert J. Motion perception in autism: a "complex" issue. J Cogn Neurosci 2003, 15:218-225.
80. Blake R., Turner L.M., Smoski M.J., Pozdol S.L., Stone W.L. Visual recognition of biological motion is impaired in children with autism. Psychol Sci 2003, 14:151-157.
81. Hazlett H.C., Poe M.D., Lightbody A.A., et al. Teasing apart the heterogeneity of autism: same behavior, different brains in toddlers with fragile X syndrome and autism. J Neurodev Disord 2009, 1:81-90.
82. Hagerman R.J., Miller L.J., McGrath-Clarke J., et al. Influence of stimulants on electrodermal studies in fragile X syndrome. Microsc Res Tech 2002, 57:168-173.
83. Roberts J.E., Boccia M.L., Bailey D.B., Hatton D.D., Skinner M. Cardiovascular indices of physiological arousal in boys with fragile X syndrome. Dev Psychobiol 2001, 39:107-123.
84. Roberts J.E., Boccia M.L., Hatton D.D., Skinner M.L., Sideris J. Temperament and vagal tone in boys with fragile X syndrome. J Dev Behav Pediatr 2006, 27:193-201.
85. Boccia M.L., Roberts J.E. Behavior and autonomic nervous system function assessed via heart period measures: the case of hyperarousal in boys with fragile X syndrome. Behav Res Methods, Instrum Comput 2000, 32:5-10.
86. Cohen I.L. A theoretical analysis of the role of hyperarousal in the learning and behavior of fragile X males. Ment Retard Dev Disabil Res Rev 1995, 1:286-291.
87. Frankland P.W., Wang Y., Rosner B., et al. Sensorimotor gating abnormalities in young males with fragile X syndrome and FMR1-knockout mice. Mol Psychiatry 2004, 9:417-425.
88. Hessl D., Berry-Kravis E., Cordeiro L., et al. Prepulse inhibition in fragile X syndrome: feasibility, reliability, and implications for treatment. Am J Med Genet B Neuropsychiatr Genet 2009, 150B:545-553.
89. Perry W., Minassian A., Lopez B., Maron L., Lincoln A. Sensorimotor gating deficits in adults with autism. Biol Psychiatry 2007, 61:482-486.
90. Postma P., Kumari V., Hines M., Gray J.A. The relationship between prepulse detection and prepulse inhibition of the acoustic startle reflex. Psychophysiology 2001, 38:377-382.
91. Greenough W.T., Klintsova A.Y., Irwin S.A., Galvez R., Bates K.E., Weiler I.J. Synaptic regulation of protein synthesis and the fragile X protein. Proc Natl Acad Sci U S A 2001, 98:7101-7106.
92. McBride S.M., Choi C.H., Wang Y., et al. Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome. Neuron 2005, 45:753-764.
93. Bakker C.E., Oostra B.A. Understanding fragile X syndrome: insights from animal models. Cytogenet Genome Res 2003, 100:111-123.
94. Zhang Y.Q., Bailey A.M., Matthies H.J., et al. Drosophila fragile X-related gene regulates the MAP1B homolog Futsch to control synaptic structure and function. Cell 2001, 107:591-603.
95. Dockendorff T.C., Su H.S., McBride S.M., et al. Drosophila lacking dfmr1 activity show defects in circadian output and fail to maintain courtship interest. Neuron 2002, 34:973-984.
96. Morales J., Hiesinger P.R., Schroeder A.J., et al. Drosophila fragile X protein, DFXR, regulates neuronal morphology and function in the brain. Neuron 2002, 34:961-972.
97. Lee A., Li W., Xu K., Bogert B.A., Su K., Gao F.B. Control of dendritic development by the Drosophila fragile X-related gene involves the small GTPase Rac1. Development 2003, 130:5543-5552.
98. Dolen G., Osterweil E., Rao B.S., et al. Correction of fragile X syndrome in mice. Neuron 2007, 56:955-962.
99. Bear M.F., Dolen G., Osterweil E., Nagarajan N. Fragile X: translation in action. Neuropsychopharmacology 2008, 33:84-87.
100. Penagarikano O., Mulle J.G., Warren S.T. The pathophysiology of fragile X syndrome. Annu Rev Genomics Hum Genet 2007, 8:109-129.
101. Bear M.F., Huber K.M., Warren S.T. The mGluR theory of fragile X mental retardation. Trends Neurosci 2004, 27:370-377.
102. Bear M.F. Therapeutic implications of the mGluR theory of fragile X mental retardation. Genes Brain Behav 2005, 4:393-398.
103. Comery T.A., Harris J.B., Willems P.J., et al. Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits. Proc Natl Acad Sci U S A 1997, 94:5401-5404.
104. Nimchinsky E.A., Oberlander A.M., Svoboda K. Abnormal development of dendritic spines in FMR1 knock-out mice. J Neurosci 2001, 21:5139-5146.
105. Irwin S.A., Patel B., Idupulapati M., et al. Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am J Med Genet A 2001, 98:161-167.
106. Knott G.W., Holtmaat A., Wilbrecht L., Welker E., Svoboda K. Spine growth precedes synapse formation in the adult neocortex in vivo. Nat Neurosci 2006, 9:1117-1124.
107. Linden D.J. Input-specific induction of cerebellar long-term depression does not require presynaptic alteration. Learn Mem 1994, 1:121-128.
108. Anwyl R. Metabotropic glutamate receptors: electrophysiological properties and role in plasticity. Brain Res Brain Res Rev 1999, 29:83-120.
109. Huber K.M., Gallagher S.M., Warren S.T., Bear M.F. Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc Natl Acad Sci U S A 2002, 99:7746-7750.
110. Zheng F., Gallagher J.P. Metabotropic glutamate receptors are required for the induction of long-term potentiation. Neuron 1992, 9:163-172.
111. Fendt M., Schmid S. Metabotropic glutamate receptors are involved in amygdaloid plasticity. Eur J Neurosci 2002, 15:1535-1541.
112. Koekkoek S.K., Yamaguchi K., Milojkovic B.A., et al. Deletion of FMR1 in Purkinje jells enhances parallel fiber LTD, enlarges spines, and attenuates cerebellar eyelid conditioning in fragile X syndrome. Neuron 2005, 47:339-352.
113. Nakamoto M., Nalavadi V., Epstein M.P., Narayanan U., Bassell G.J., Warren S.T. Fragile X mental retardation protein deficiency leads to excessive mGluR5-dependent internalization of AMPA receptors. Proc Natl Acad Sci U S A 2007, 104:15537-15542.
114. Irwin S.A., Galvez R., Weiler I.J., Beckel-Mitchener A., Greenough W.T. Brain structure and functions of FMR1 protein. Fragile X syndrome: diagnosis, treatment, and research 2002, 191-205. Johns Hopkins University Press, Baltimore. 3rd ed. R.J. Hagerman, P.J. Hagerman (Eds.).
115. Beckel-Mitchener A., Greenough W.T. Correlates across the structural, functional, and molecular phenotypes of fragile X syndrome. Ment Retard Dev Disabil Res Rev 2004, 10:53-59.
116. Chuang S.C., Zhao W., Bauchwitz R., Yan Q., Bianchi R., Wong R.K. Prolonged epileptiform discharges induced by altered group I metabotropic glutamate receptor-mediated synaptic responses in hippocampal slices of a fragile X mouse model. J Neurosci 2005, 25:8048-8055.
117. Gasparini F., Lingenhohl K., Stoehr N., et al. 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology 1999, 38:1493-1503.
118. Yan Q.J., Rammal M., Tranfaglia M., Bauchwitz R.P. Suppression of two major fragile X syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology 2005, 49:1053-1066.
119. de Vrij F.M., Levenga J., van der Linde H.C., et al. Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice. Neurobiol Dis 2008, 31:127-132.
120. Paredes R.G., Agmo A. GABA and behavior: the role of receptor subtypes [Erratum in: Neurosci Biobehav Rev 1992;16:425]. Neurosci Biobehav Rev 1992, 16:145-170.
121. Mihalek R.M., Banerjee P.K., Korpi E.R., et al. Attenuated sensitivity to neuroactive steroids in γ-aminobutyrate type A receptor delta subunit knockout mice. Proc Natl Acad Sci U S A 1999, 96:12905-12910.
122. A receptor. J Pharmacol Exp Ther 1997, 280:1284-1295.
123. Miyashiro K.Y., Beckel-Mitchener A., Purk T.P., et al. RNA cargoes associating with FMRP reveal deficits in cellular functioning in Fmr1 null mice. Neuron 2003, 37:417-431.
124. A receptor in fragile X syndrome. Brain Res 2006, 1121:238-245.
125. A receptor subunit delta in the fragile X knockout mouse model. Neurobiol Dis 2006, 21:346-357.
126. Chang S., Bray S.M., Li Z., et al. Identification of small molecules rescuing fragile X syndrome phenotypes in Drosophila. Nat Chem Biol 2008, 4:256-263.
127. B-mediated presynaptic inhibition of excitatory transmission and synaptic vesicle dynamics in cultured hippocampal neurons. Neuron 1997, 18:143-152.
128. + currents by muscarinic and metabotropic glutamate receptors in immature rat hippocampus. J Physiol 2007, 580:411-422.
129. Primrose D.A. Treatment of self-injurious behaviour with a GABA (γ-aminobutyric acid) analogue. J Ment Defic Res 1979, 23:163-173.
130. Paylor R. Pharmacological modification of behavioral responses in the fragile X mouse model. Proc Int Fragile X Conf 11th 2008, 11:1052. (abstract) http://www.fragilex.org/html/2008_proceedings.htm.
131. B receptor-mediated signaling reduces the susceptibility of fragile X knockout mice to audiogenic seizures. Mol Pharmacol 2009, 76:18-24.
132. Porter R.H., Jaeschke G., Spooren W., et al. Fenobam: a clinically validated nonbenzodiazepine anxiolytic is a potent, selective, and noncompetitive mGlu5 receptor antagonist with inverse agonist activity. J Pharmacol Exp Ther 2005, 315:711-721.
133. Berry-Kravis E., Hessl D., Coffey S., et al. A pilot open label, single dose trial of fenobam in adults with fragile X syndrome. J Med Genet 2009, 46:266-271.
134. Hagerman R.J., Berry-Kravis E., Kaufmann W.E., et al. Advances in the treatment of fragile X syndrome. Pediatrics 2009, 123:378-390.
135. Berry-Kravis E., Sumis A., Hervey C., et al. Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome. J Dev Behav Pediatr 2008, 29:293-302.
136. Li J., Pelletier M.R., Perez Velazquez J.L., Carlen P.L. Reduced cortical synaptic plasticity and GluR1 expression associated with fragile X mental retardation protein deficiency. Mol Cell Neurosci 2002, 19:138-151.
137. Lauterborn J.C., Rex C.S., Kramár E., et al. Brain-derived neurotrophic factor rescues synaptic plasticity in a mouse model of fragile X syndrome. J Neurosci 2007, 27:10685-10694.
138. Berry-Kravis E., Krause S.E., Block S.S., et al. Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: a controlled trial. J Child Adolesc Psychopharmacol 2006, 16:525-540.
139. Bilousova T.V., Rusakov D.A., Ethell D.W., Ethell I.M. Matrix metalloproteinase-7 disrupts dendritic spines in hippocampal neurons through NMDA receptor activation. J Neurochem 2006, 97:44-56.
140. Bilousova T.V., Dansie L., Ngo M., et al. Minocycline promotes dendritic spine maturation and improves behavioural performance in the fragile X mouse model. J Med Genet 2009, 46:94-102.
141. Utari A, Chonchaiya W, Rivera SM, et al. Side effects of minocycline treatment in patients with fragile X syndrome and exploration of outcome measures. Am J Intellect Dev Disabil (in press).
142. McCracken J.T., McGough J., Shah B., et al. Risperidone in children with autism and serious behavioral problems. N Engl J Med 2002, 347:314-321.
143. Aman M.G., Gharabawi G.M. Treatment of behavior disorders in mental retardation: report on transitioning to atypical antipsychotics, with an emphasis on risperidone. J Clin Psychiatry 2004, 65:1197-1210. Special Topic Advisory Panel on Transitioning to Risperidone Therapy in Patients With Mental Retardation and Developmental Disabilities.
144. Owen R., Sikich L., Marcus R.N., et al. Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Pediatrics 2009, 124:1533-1540.
145. Erickson C.A., Kohn A.E., Diener J.T., Stigler K.A., Posey D.J., McDougle C.J. A prospective, 12-week open-label study of aripiprazole in fragile X syndrome. Proc Int Fragile X Conf 11th 2008, 11:1065-1100. http://www.fragilex.org/html/2008_proceedings.htm.