The psychiatric presentation of fragile X: Evolution of the diagnosis and treatment of the psychiatric comorbidities of fragile X syndrome

Developmental Neuroscience

Volumn 33, Issue 5, 2011, Pages 337-348

  Tranfaglia, Michael R ^a  

^a FRAXA Research Foundation   (United States)

Author keywords

Autism spectrum disorders; Behavior; Disease mechanisms; Pathophysiology; Phenotype; Psychopharmacology

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR STIMULATING AGENT; 6 QUINOXALINECARBOXYLIC ACID PIPERIDIDE; ACAMPROSATE; ANTICONVULSIVE AGENT; ANTIDEPRESSANT AGENT; ARBACLOFEN; ATYPICAL ANTIPSYCHOTIC AGENT; BENZODIAZEPINE DERIVATIVE; CLONIDINE; FENOBAM; FOLIC ACID; FRAGILE X MENTAL RETARDATION PROTEIN; GABOXADOL; GLYCOGEN SYNTHASE KINASE 3BETA; GUANFACINE; HYDROCORTISONE; LEVACECARNINE; LITHIUM; MEMANTINE; METABOTROPIC RECEPTOR ANTAGONIST; MIFEPRISTONE; MINOCYCLINE; OCTAHYDRO 4 HYDROXY 4 [(3 METHYLPHENYL)ETHYNYL] 1H INDOLE 1 CARBOXYLIC ACID METHYL ESTER; PLACEBO; PSYCHOSTIMULANT AGENT; RO 4917523; SEROTONIN UPTAKE INHIBITOR; STX 107; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROIC ACID;

AGGRESSION; ANXIETY DISORDER; ATTENTION DEFICIT DISORDER; ATTENTION DISTURBANCE; AUTISM; AUTOMUTILATION; AUTONOMIC DYSFUNCTION; BEHAVIOR DISORDER; BEHAVIORAL DISINHIBITION; COMORBIDITY; DIAGNOSTIC ACCURACY; DIAGNOSTIC AND STATISTICAL MANUAL OF MENTAL DISORDERS; DRUG EFFICACY; FECES INCONTINENCE; FRAGILE X SYNDROME; GASTROINTESTINAL SYMPTOM; GENE MUTATION; HISTORY OF MEDICINE; HUMAN; HYDROCORTISONE RELEASE; HYPERACTIVITY; IMPULSIVENESS; IRRITABILITY; LOW DRUG DOSE; MENTAL DISEASE; MOOD DISORDER; NERVE CELL PLASTICITY; NONHUMAN; PANIC; PHENOTYPE; PHOBIA; PRESCRIPTION; PRIORITY JOURNAL; PROTEIN SYNTHESIS; PSYCHIATRIC DIAGNOSIS; REVIEW; SCHIZOPHRENIA; SIDE EFFECT; STEREOTYPY; SYNAPTOGENESIS; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT;

ANIMALS; BEHAVIOR; COMORBIDITY; FRAGILE X MENTAL RETARDATION PROTEIN; FRAGILE X SYNDROME; HUMANS; MENTAL DISORDERS; PHENOTYPE;

EID: 83055181288     PISSN: 03785866     EISSN: 14219859     Source Type: Journal    
DOI: 10.1159/000329421     Document Type: Review

References (98)

1. Aman MG, Singh NN, Stewart AW, Field CJ (1985): The aberrant behavior checklist: a behavior rating scale for the assessment of treatment effects. Am J Ment Defic 89: 485-491.
2. Backes M, Gena B, Schreck J, Doerfler W, Lehmkuhl G, von Gontard A (2000): Cognitive and behavioral profile of fragile X boys: correlations to molecular data. Am J Med Genet 95: 150-156.
3. Bailey DB Jr, Hatton DD, Skinner M, Mesibov G (2001): Autistic behavior, FMR1 protein, and developmental trajectories in young males with fragile X syndrome. J Autism Dev Disord 31: 165-174.
4. Baumgardner TL, Reiss AL, Freund LS, Abrams MT (1995): Specification of the neurobehavioral phenotype in males with fragile X syndrome. Pediatrics 95: 744-752.
5. Bear MF, Huber KM, Warren ST (2004): The mGluR theory of fragile X mental retardation. Trends Neurosci 27: 370-377.
6. Bear MF (2005): Therapeutic implications of the mGluR theory of fragile X mental retardation. Genes Brain Behav 4: 393-398.
7. Berry-Kravis E, Hessl D, Coffey S, Hervey C, Schneider A, Yuhas J, Hutchison J, Snape M, Tranfaglia M, Nguyen DV, Hagerman R (2009): A pilot open label, single dose trial of fenobam in adults with fragile X syndrome. J Med Genet 46: 266-271.
8. Berry-Kravis E, Krause SE, Block SS, Guter S, Wuu J, Leurgans S, Decle P, Potanos K, Cook E, Salt J, Maino D, Weinberg D, Lara R, Jardini T, Cogswell J, Johnson SA, Hagerman R (2006): Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: a controlled trial. J Child Adolesc Psychopharmacol 16: 525-540.
9. Berry-Kravis E, Potanos K (2004): Psychopharmacology in fragile X syndrome - present and future. Ment Retard Dev Disabil Res Rev 10: 42-48.
10. Berry-Kravis E, Sumis A, Hervey C, Nelson M, Porges SW, Weng N, Weiler IJ, Greenough WT (2008): Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome. J Dev Behav Pediatr 29: 293-302.
11. Bilousova TV, Dansie L, Ngo M, Aye J, Charles JR, Ethell DW, Ethell IM (2009): Minocycline promotes dendritic spine maturation and improves behavioural performance in the fragile X mouse model. J Med Genet 46: 94-102.
12. Blomquist HK, Bohman M, Edvinsson SO, Gillberg C, Gustavson KH, Holmgren G, Wahlström J (1985): Frequency of the fragile X syndrome in infantile autism. A Swedish multicenter study. Clin Genet 27: 113-117.
13. Borghgraef M, Fryns JP, Dielkens A, Pyck K, Van den Berghe H (1987): Fragile (X) syndrome: a study of the psychological profile in 23 prepubertal patients. Clin Genet 32: 179-186.
14. Boyle L, Kaufmann WE (2010): The behavioral phenotype of FMR1 mutations. Am J Med Genet Part C Semin Med Genet 154C:469-476.
15. Bregman JD, Leckman JF, Ort SI (1988): Fragile X syndrome: genetic predisposition to psychopathology. J Autism Dev Disord 18: 343-354.
16. Brown WT, Friedman E, Jenkins EC, Brooks J, Wisniewski K, Raguthu S, French JH (1982): Association of fragile X syndrome with autism. Lancet i:100.
17. Brown WT, Jenkins EC, Cohen IL, Fisch GS, Wolf-Schein EG, Gross A, Waterhouse L, Fein D, Mason-Brothers A, Ritvo E, et al (1986): Fragile X and autism: a multicenter survey. Am J Med Genet 23: 341-352.
18. Brown WT, Jenkins EC, Friedman E, Brooks J, Wisniewski K, Raguthu S, French J (1982): Autism is associated with the fragile-X syndrome. J Autism Dev Disord 12: 303-308.
19. Choi CH, Schoenfeld BP, Bell AJ, Hinchey P, Kollaros M, Gertner MJ, Woo NH, Tranfaglia MR, Bear MF, Zukin RS, McDonald TV, Jongens TA, McBride SM (2011): Pharmacological reversal of synaptic plasticity deficits in the mouse model of fragile X syndrome by group II mGluR antagonist or lithium treatment. Brain Res 1380: 106-119.
20. D'Hulst C, De Geest N, Reeve SP, Van Dam D, De Deyn PP, Hassan BA, Kooy RF (2006): Decreased expression of the GABA A receptor in fragile X syndrome. Brain Res 1121: 238-245.
21. Dobkin CS, Nolin SL, Cohen I, Sudhalter V, Bialer MG, Ding XH, Jenkins EC, Zhong N, Brown WT (1996): Tissue differences in fragile X mosaics: mosaicism in blood cells may differ greatly from skin. Am J Med Genet 64: 296-301.
22. Dockendorff TC, Su HS, McBride SM, Yang Z, Choi CH, Siwicki KK, Sehgal A, Jongens TA (2002): Drosophila lacking dfmr1 activity show defects in circadian output and fail to maintain courtship interest. Neuron 34: 973-984.
23. Dölen G, Carpenter RL, Ocain TD, Bear MF (2010): Mechanism-based approaches to treating fragile X. Pharmacol Ther 127: 78-93.
24. Einfeld SL, Hall W (1994): When is a behavioural phenotype not a phenotype? Dev Med Child Neurol 36: 467-470.
25. Einfeld SL, Tonge BJ, Florio T (1994): Behavioural and emotional disturbance in fragile X syndrome. Am J Med Genet 51: 386-391.
26. Einfeld S, Tonge B, Turner G (1999): Longitudinal course of behavioral and emotional problems in fragile X syndrome. Am J Med Genet 87: 436-439.
27. Erickson CA, Mullett JE, McDougle CJ (2009): Open-label memantine in fragile X syndrome. J Autism Dev Disord, E-pub ahead of print.
28. Erickson CA, Mullett JE, McDougle CJ (2010): Brief report: acamprosate in fragile X syndrome. J Autism Dev Disord 40: 1412-1416.
29. Erickson CA, Stigler KA, Posey DJ, McDougle CJ (2010): Aripiprazole in autism spectrum disorders and fragile X syndrome. Neurotherapeutics 7: 258-263.
30. Fatemi SH, Kneeland RE, Liesch SB, Folsom TD (2010): Fragile X mental retardation protein levels are decreased in major psychiatric disorders. Schizophr Res 124: 246-247.
31. Fisch GS, Cohen IL, Gross AC, Jenkins V, Jenkins EC, Brown WT (1988): Folic acid treatment of fragile X males: a further study. Am J Med Genet 30: 393-399.
32. Fisch GS, Cohen IL, Wolf EG, Brown WT, Jenkins EC, Gross A (1986): Autism and the fragile X syndrome. Am J Psychiatry 143: 71-73.
33. Fisch GS (1993): What is associated with the fragile X syndrome? Am J Med Genet 48: 112-121.
34. Fryns JP (1984): The fragile X syndrome. A study of 83 families. Clin Genet 26: 497-528.
35. Fryns JP, Jacobs J, Kleczkowska A, van den Berghe H (1984): The psychological profile of the fragile X syndrome. Clin Genet 25: 131-134.
36. Fulks JL, O'Bryhim BE, Wenzel SK, Fowler SC, Vorontsova E, Pinkston JW, Ortiz AN, Johnson MA (2010): Dopamine release and uptake impairments and behavioral alterations observed in mice that model fragile X mental retardation syndrome. ACS Chem Neurosci 1: 679-690.
37. Gibson JR, Bartley AF, Hays SA, Huber KM (2008): Imbalance of neocortical excitation and inhibition and altered UP states reflect network hyperexcitability in the mouse model of fragile X syndrome. J Neurophysiol 100: 2615-2626.
38. Gillberg C, Persson E, Wahlström J (1986): The autism-fragile-X syndrome (AFRAX): a population-based study of ten boys. J Ment Defic Res 30: 27-39.
39. Hagerman RJ, Berry-Kravis E, Kaufmann WE, Ono MY, Tartaglia N, Lachiewicz A, Kronk R, Delahunty C, Hessl D, Visootsak J, Picker J, Gane L, Tranfaglia M (2009): Advances in the treatment of fragile X syndrome. Pediatrics 123: 378-390.
40. Hagerman RJ, Miller LJ, McGrath-Clarke J, Riley K, Goldson E, Harris SW, Simon J, Church K, Bonnell J, Ognibene TC, McIntosh DN (2002): Influence of stimulants on electrodermal studies in fragile X syndrome. Microsc Res Tech 57: 168-173.
41. Hagerman RJ, Murphy MA, Wittenberger MD (1988): A controlled trial of stimulant medication in children with the fragile X syndrome. Am J Med Genet 30: 377-392.
42. Hall SS, Burns DD, Lightbody AA, Reiss AL (2008): Longitudinal changes in intellectual development in children with fragile X syndrome. J Abnorm Child Psychol 36: 927-939.
43. Hall S, DeBernardis M, Reiss A (2006): Social escape behaviors in children with fragile X syndrome. J Autism Dev Disord 36: 935-947.
44. Hall SS, Lightbody AA, Hirt M, Rezvani A, Reiss AL (2010): Autism in fragile X syndrome: a category mistake? J Am Acad Child Adolesc Psychiatry 49: 921-933.
45. Hall SS, Lightbody AA, Huffman LC, Lazzeroni LC, Reiss AL (2009): Physiological correlates of social avoidance behavior in children and adolescents with fragile x syndrome. J Am Acad Child Adolesc Psychiatry 48: 320-329.
46. Hall SS, Lightbody AA, Reiss AL (2008): Compulsive, self-injurious, and autistic behavior in children and adolescents with fragile X syndrome Am J Ment Retard 113: 44-53.
47. Harpey JP (1982): Treatment of fragile-X. Pediatrics 69: 670.
48. Hessl D, Glaser B, Dyer-Friedman J, Blasey C, Hastie T, Gunnar M, Reiss AL (2002): Cortisol and behavior in fragile X syndrome. Psychoneuroendocrinology 27: 855-872.
49. Hessl D, Nguyen DV, Green C, Chavez A, Tassone F, Hagerman RJ, Senturk D, Schneider A, Lightbody A, Reiss AL, Hall S (2009): A solution to limitations of cognitive testing in children with intellectual disabilities: the case of fragile X syndrome. J Neurodev Disord 1: 33-45.
50. Hessl D, Tassone F, Cordeiro L, Koldewyn K, McCormick C, Green C, Wegelin J, Yuhas J, Hagerman RJ (2008): Brief report: aggression and stereotypic behavior in males with fragile X syndrome - Moderating secondary genes in a 'single gene' disorder. J Autism Dev Disord 38: 184-189.
51. Kiefer F, Mann K (2010): Acamprosate: how, where, and for whom does it work? Mechanism of action, treatment targets, and individualized therapy. Curr Pharm Des 16: 2098-2102.
52. King BH, Hollander E, Sikich L, McCracken JT, Scahill L, Bregman JD, Donnelly CL, Anagnostou E, Dukes K, Sullivan L, Hirtz D, Wagner A, Ritz L, STAART Psychopharmacology Network (2009): Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism. Arch Gen Psychiatry 66: 583-590.
53. Kolevzon A, Mathewson KA, Hollander E (2006): Selective serotonin reuptake inhibitors in autism: a review of efficacy and tolerability. J Clin Psychiatry 67: 407-414.
54. Lachiewicz AM, Spiridigliozzi GA, Gullion CM, Ransford SN, Rao K (1994): Aberrant behaviors of young boys with fragile X syndrome. Am J Ment Retard 98: 567-579.
55. Largo RH, Schinzel A (1985): Developmental and behavioural disturbances in 13 boys with fragile X syndrome. Eur J Pediatr 143: 269-275.
56. Levkovitz Y, Mendlovich S, Riwkes S, Braw Y, Levkovitch-Verbin H, Gal G, Fennig S, Treves I, Kron S (2010): A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia. J Clin Psychiatry 71: 138-149.
57. Li X, Jope RS (2010): Is glycogen synthase kinase- 3 a central modulator in mood regulation? Neuropsychopharmacology 35: 2143-2154.
58. Liu ZH, Chuang DM, Smith CB (2010): Lithium ameliorates phenotypic deficits in a mouse model of fragile X syndrome. Int J Neuropsychopharmacol 25: 1-13.
59. Markham JA, Beckel-Mitchener AC, Estrada CM, Greenough WT (2006): Corticosterone response to acute stress in a mouse model of Fragile X syndrome. Psychoneuroendocrinology 31: 781-785.
60. Marrosu F, Marrosu G, Rachel MG, Biggio G (1987): Paradoxical reactions elicited by diazepam in children with classic autism. Funct Neurol 2: 355-361.
61. McDougle CJ, Naylor ST, Cohen DJ, Volkmar FR, Heninger GR, Price LH (1996): A doubleblind, placebo-controlled study of fluvoxamine in adults with autistic disorder. Arch Gen Psychiatry 53: 1001-1008.
62. McDougle CJ, Stigler KA, Erickson CA, Posey DJ (2008): Atypical antipsychotics in children and adolescents with autistic and other pervasive developmental disorders. J Clin Psychiatry 69(suppl 4):15-20.
63. Mines MA, Yuskaitis CJ, King MK, Beurel E, Jope RS (2010): GSK3 influences social preference and anxiety-related behaviors during social interaction in a mouse model of fragile X syndrome and autism. PLoS One 5:e9706.
64. Moon J, Beaudin AE, Verosky S, Driscoll LL, Weiskopf M, Levitsky DA, Crnic LS, Strupp BJ (2006): Attentional dysfunction, impulsivity, and resistance to change in a mouse model of fragile X syndrome. Behav Neurosci 120: 1367-1379.
65. Munir F, Cornish KM, Wilding J (2000): A neuropsychological profile of attention deficits in young males with fragile X syndrome. Neuropsychologia 38: 1261-1270.
66. Musumeci SA, Hagerman RJ, Ferri R, Bosco P, Dalla Bernardina B, Tassinari CA, De Sarro GB, Elia M (1999): Epilepsy and EEG findings in males with fragile X syndrome. Epilepsia 40: 1092-1099.
67. Nakamoto M, Nalavadi V, Epstein MP, Narayanan U, Bassell GJ, Warren ST (2007): Fragile X mental retardation protein deficiency leads to excessive mGluR5-dependent internalization of AMPA receptors. Proc Natl Acad Sci USA 104: 15537-15542.
68. Olmos-Serrano JL, Paluszkiewicz SM, Martin BS, Kaufmann WE, Corbin JG, Huntsman MM (2010): Defective GABAergic neurotransmission and pharmacological rescue of neuronal hyperexcitability in the amygdale in a mouse model of fragile X syndrome. J Neurosci 30: 9929-9938.
69. Pacey LK, Heximer SP, Hampson DR (2009): Increased GABA(B) receptor-mediated signaling reduces the susceptibility of fragile X knockout mice to audiogenic seizures. Mol Pharmacol 76: 18-24.
70. Paribello C, Tao L, Folino A, Berry-Kravis E, Tranfaglia M, Ethell IM, Ethell DW (2010): Open-label add-on treatment trial of minocycline in fragile X syndrome. BMC Neurol 10: 91.
71. Pieretti M, Zhang F, Fu Y H, Warren ST, Oostra BA, Caskey CT, Nelson DL (1991): Absence of expression of the FMR-1 gene in Fragile X syndrome. Cell 66: 817-822.
72. Posey DJ, McDougle CJ (2000): The pharmacotherapy of target symptoms associated with autistic disorder and other pervasive developmental disorders. Harv Rev Psychiatry 8: 45-63.
73. Qin M, Smith CB (2008): Unaltered hormonal response to stress in a mouse model of fragile X syndrome. Psychoneuroendocrinology 33: 883-889.
74. Reiss AL, Freund L (1992): Behavioral phenotype of fragile X syndrome: DSM-III-R autistic behavior in male children. Am J Med Genet 43: 35-46.
75. Roberts JE, Symons FJ, Johnson AM, Hatton DD, Boccia ML (2005): Blink rate in boys with fragile X syndrome: preliminary evidence for altered dopamine function. J Intellect Disabil Res 49: 647-656.
76. Rubenstein J, Merzenich M (2003): Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes Brain Behav 2: 255-267.
77. Sabaratnam M, Vroegop PG, Gangadharan SK (2001): Epilepsy and EEG findings in 18 males with fragile X syndrome. Seizure 10: 60-63.
78. Solomon M, Ozonoff S, Carter C, Caplan R (2008): Formal thought disorder and the autism spectrum: relationship with symptoms, executive control, and anxiety. J Autism Dev Disord 38: 1474-1484.
79. Steinhausen HC, Von Gontard A, Spohr HL, Hauffa BP, Eiholzer U, Backes M, Willms J, Malin Z (2002): Behavioral phenotypes in four mental retardation syndromes: fetal alcohol syndrome, Prader-Willi syndrome, fragile X syndrome, and tuberosis sclerosis. Am J Med Genet 111: 381-387.
80. Strom CM, Brusca RM, Pizzi WJ (1992): Doubleblind, placebo-controlled crossover study of folinic acid (Leucovorin) for the treatment of fragile X syndrome. Am J Med Genet 44: 676-682.
81. Sullivan K, Hatton D, Hammer J, Sideris J, Hooper S, Ornstein P, Bailey D Jr (2006): ADHD symptoms in children with FXS. Am J Med Genet A 140: 2275-2288.
82. Torrioli MG, Vernacotola S, Peruzzi L, Tabolacci E, Mila M, Militerni R, Musumeci S, Ramos FJ, Frontera M, Sorge G, Marzullo E, Romeo G, Vallee L, Veneselli E, Cocchi E, Garbarino E, Moscato U, Chiurazzi P, D'Iddio S, Calvani M, Neri G (2008): A double-blind, parallel, multicenter comparison of L -acetylcarnitine with placebo on the attention deficit hyperactivity disorder in fragile X syndrome boys. Am J Med Genet A 146: 803-812.
83. Torrioli M, Vernacotola S, Setini C, Bevilacqua F, Martinelli D, Snape M, Hutchison JA, Di Raimo FR, Tabolacci E, Neri G (2010): Treatment with valproic acid ameliorates ADHD symptoms in fragile X syndrome boys. Am J Med Genet A 152A:1420-1427.
84. Tsiouris JA, Brown WT (2004): Neuropsychiatric symptoms of fragile X syndrome: pathophysiology and pharmacotherapy. CNS Drugs 18: 687-703.
85. Veenema H, Veenema T, Geraedts JP (1987): The fragile X syndrome in a large family. 2. Psychological investigations. J Med Genet 24: 32-38.
86. Ventura R, Pascucci T, Catania MV, Musumeci SA, Puglisi-Allegra S (2004): Object recognition impairment in Fmr1 knockout mice is reversed by amphetamine: involvement of dopamine in the medial prefrontal cortex. Behav Pharmacol 15: 433-442.
87. Volkow ND, Wang GJ, Newcorn JH, Kollins SH, Wigal TL, Telang F, Fowler JS, Goldstein RZ, Klein N, Logan J, Wong C, Swanson JM (2010): Motivation deficit in ADHD is associated with dysfunction of the dopamine reward pathway. Mol Psychiatry, E-pub ahead of print
88. Wahlström J, Gillberg C, Gustavson KH, Holmgren G (1986): Infantile autism and the fragile X. A Swedish multicenter study. Am J Med Genet 23: 403-408.
89. Wang H, Wu LJ, Kim SS, Lee FJ, Gong B, Toyoda H, Ren M, Shang YZ, Xu H, Liu F, Zhao MG, Zhuo M (2008): FMRP acts as a key messenger for dopamine modulation in the forebrain. Neuron 59: 634-647.
90. Weiler IJ, Irwin SA, Klintsova AY, Spencer CM, Brazelton AD, Miyashiro K, Comery TA, Patel B, Eberwine J, Greenough WT (1997): Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation. Proc Natl Acad Sci USA 94: 5395-5400.
91. Wiegers AM, DeVries LB, Curfs LM, Fryns JP (1993): Identical psychological profile and behaviour pattern in different types of mutation in the FMR-1 region. Clin Genet 43: 326-327.
92. Williams K, Wheeler DM, Silove N, Hazell P (2010): Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). Cochrane Database Syst Rev 8:CD004677.
93. Yan QJ, Asafo-Adjei PK, Arnold HM, Brown RE, Bauchwitz RP (2004): A phenotypic and molecular characterization of the fmr1-tm1Cgr fragile X mouse. Genes Brain Behav 3: 337-359.
94. Yan QJ, Rammal M, Tranfaglia M, Bauchwitz RP (2005): Suppression of two major fragile X syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology 49: 1053-1066.
95. Zhang YQ, Friedman DB, Wang Z, Woodruff E 3rd, Pan L, O'Donnell J, Broadie K (2005): Protein expression profiling of the drosophila fragile X mutant brain reveals up-regulation of monoamine synthesis. Mol Cell Proteomics 4: 278-290.
96. Zupan B, Toth M (2008a): Wild-type male offspring of fmr-1+/- mothers exhibit characteristics of the fragile X phenotype. Neuropsychopharmacology 33: 2667-2675.
97. Zupan B, Toth M (2008b): Inactivation of the maternal fragile X gene results in sensitization of GABAB receptor function in the offspring. J Pharmacol Exp Ther 327: 820-826.
98. Aman M.G. Singh N.N. Stewart A.W. Field C.J. The aberrant behavior checklist: A behavior rating scale for the assessment of treatment effects American Journal of Mental Deficiency 1985 89 5 485-491