CNS Drugs

, Volume 18, Issue 11, pp 687–703 | Cite as

Neuropsychiatric Symptoms of Fragile X Syndrome

Pathophysiology and Pharmacotherapy
Therapy in Practice


Fragile X syndrome is the leading inherited form of mental retardation, and second only to Down’s syndrome as a cause of mental retardation attributable to an identifiable genetic abnormality. Fragile X syndrome is caused by a defect in the fragile X mental retardation 1 gene (FMR1), located near the end of the long arm of the X chromosome. FMR1 normally synthesises the fragile X protein (FMRP), but mutations in FMR1 lead to a lack of FMRP synthesis, resulting in fragile X syndrome. While the specific function of FMRP is not yet fully understood, the protein is known to be important for normal brain development. The physical, cognitive and behavioural features of individuals with fragile X syndrome depend on gender (females have two X chromosomes, one active and one inactive) and the molecular status of the mutation (premutation, full mutation or mosaic). Features of the behavioural profile of individuals with fragile X syndrome include hypersensitivity to stimuli, overarousability, inattention, hyperactivity and (mostly in men) explosive and aggressive behaviour to others or self. Social anxiety, other anxiety disorders, depression, impulse control disorder and mood disorders are the most common psychiatric disorders diagnosed in individuals with fragile X syndrome, although no formal studies have been undertaken.

There have been very few psychopharmacological studies of the treatment of behaviours associated with fragile X syndrome. These limited studies and surveys of psychotropic drugs used in individuals with fragile X syndrome suggest that stimulants are helpful for hyperactivity, that α2-adrenoceptor agonists and β-adrenoceptor antagonists help to control overarousability, impulsivity and aggressiveness, and that SSRIs can control anxiety, impulsivity and irritability, alleviate depressive symptoms and decrease aggressive and self-injurious behaviour. Typical and atypical antipsychotics in combination with other psychotropics have been used for control of psychotic disorders and severe aggressive behaviours. Mood stabilisers have been found to be useful when mood dysregulation or mood disorders are present with or without aggressive behaviour. Folic acid and L-acetylcarnitine (levacecarnine) have not been found to improve deficits or behaviours. As there is no specific psychotropic drug for any of the deficits or behaviours associated with fragile X syndrome, clinicians are advised to diagnose any psychiatric syndromes or disorders present and treat them with the appropriate psychotropic drug.

If no psychiatric disorder can be diagnosed and the patient’s challenging behaviours cannot be controlled with environmental manipulation or behaviour modification techniques, the most benign psychotropic drug should be used. Antipsychotics should be reserved for psychotic disorders, for impulse control disorders (used in combination with other psychotropics), or when challenging behaviours constitute an emergency. In the future, new medications targeting molecules implicated in the modulation of anxiety, fear and fear responding will be useful for treating the social anxiety and overarousability exhibited by individuals with fragile X syndrome.


Clonidine Social Anxiety Intellectual Disability Atomoxetine Piracetam 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors would like to thank Joan Maffei for her technical assistance in the preparation of this review. The authors were supported by the NYS Office of Mental Retardation and Developmental Disabilities. No funding was used in the preparation of this review. The authors have no potential conflicts of interest directly related to the content of this review.


  1. 1.
    O’Donnell WT, Warren ST. A decade of molecular studies of fragile X syndrome. Annu Rev Neurosci 2002; 25: 315–38PubMedCrossRefGoogle Scholar
  2. 2.
    Brown WT. The molecular biology of the fragile X mutation. In: Hagerman RJ, Hagerman PJ, editors. Fragile X syndrome: diagnosis, treatment and research. 3rd ed. Baltimore (MD): Johns Hopkins University Press, 2002: 110–35Google Scholar
  3. 3.
    Nolin SL, Lewis French III A, Ye LL, et al. Familial transmission of the FMR1 CGG repeat. Am J Hum Genet 1996; 59: 1252–61PubMedGoogle Scholar
  4. 4.
    Brown WT, Houck Jr GE, Jeziorowska A, et al. Rapid fragile X carrier screening and prenatal diagnosis using a nonradioactive PCR test. JAMA 1993; 270(13): 1569–75PubMedCrossRefGoogle Scholar
  5. 5.
    Hagerman RJ. Physical and behavioral phenotype. In: Hagerman RJ, Cronister A, editors. Fragile X syndrome: diagnosis, treatment and research. 3rd ed. Baltimore (MD): Johns Hopkins University Press, 2002: 3–109Google Scholar
  6. 6.
    Sobesky WE, Hull CE, Hagerman RJ. Symptoms of schizotypal personality disorder in fragile X women. J Am Acad Child Adolesc Psychiatry 1994; 33(2): 247–55PubMedCrossRefGoogle Scholar
  7. 7.
    Sobesky WE, Pennington BF, Porter D, et al. Emotional and neurocognitive deficits in fragile X. Am J Med Genet 1994; 51(4): 378–85PubMedCrossRefGoogle Scholar
  8. 8.
    Franke P, Maier W, Hautzinger M, et al. Fragile-X carrier females: evidence for a distinct psychopathological phenotype? Am J Med Genet 1996; 64(2): 334–9PubMedCrossRefGoogle Scholar
  9. 9.
    Franke P, Leboyer M, Gansicke M, et al. Genotype-phenotype relationship in female carriers of the premutation and full mutation of FMR-1. Psychiatry Res 1998; 80(2): 113–27PubMedCrossRefGoogle Scholar
  10. 10.
    Lachiewicz AM, Dawson DV. Behavior problems of young girls with fragile X syndrome: factor scores on the Conners’ Parent’s Questionnaire. Am J Med Genet 1994; 51(4): 364–9PubMedCrossRefGoogle Scholar
  11. 11.
    Freund LS, Reiss AL, Abrams MT. Psychiatric disorders associated with fragile X in the young female. Pediatrics 1993; 91(2): 321–9PubMedGoogle Scholar
  12. 12.
    Sobesky WE, Taylor AK, Pennington BF, et al. Molecular/clinical correlations in females with fragile X. Am J Med Genet 1996; 64(2): 340–5PubMedCrossRefGoogle Scholar
  13. 13.
    Riddle JE, Cheema A, Sobesky WE, et al. Phenotypic involvement in females with the FMR1 gene mutation. Am J Ment Retard 1998; 102(6): 590–601PubMedCrossRefGoogle Scholar
  14. 14.
    Abrams MT, Reiss AL, Freund LS, et al. Molecular-neurobehavioral associations in females with the fragile X full mutation. Am J Med Genet 1994; 51(4): 317–27PubMedCrossRefGoogle Scholar
  15. 15.
    Rousseau F, Heitz D, Tarleton J, et al. A multicenter study on genotype-phenotype correlations in the fragile X syndrome, using direct diagnosis with probe StB12.3: the first 2,253 cases. Am J Hum Genet 1994; 55(2): 225–37PubMedGoogle Scholar
  16. 16.
    de Vries BB, Wiegers AM, Smits AP, et al. Mental status of females with an FMR1 gene full mutation. Am J Med Genet 1996; 58: 1025–32Google Scholar
  17. 17.
    Mazzocco MM, Pennington BF, Hagerman RJ. The neurocognitive phenotype of female carriers of fragile X: additional evidence for specificity. J Dev Behav Pediatr 1993; 14(5): 328–35PubMedCrossRefGoogle Scholar
  18. 18.
    Bennetto L, Pennington BF. Neuropsychology. In: Hagerman RJ, Hagerman PJ, editors. Fragile X syndrome: diagnosis, treatment and research. 3rd ed. Baltimore (MD): Johns Hopkins University Press 2002: 206–48Google Scholar
  19. 19.
    Merenstein SA, Sobesky WE, Taylor AK, et al. Molecular-clinical correlations in males with an expanded FMR1 mutation. Am J Med Genet 1996; 64(2): 388–94PubMedCrossRefGoogle Scholar
  20. 20.
    Hagerman RJ, Hull CE, Safanda JF, et al. High functioning fragile X males: demonstration of an unmethylated fully expanded FMR-1 mutation associated with protein expression. Am J Med Genet 1994; 51(4): 298–308PubMedCrossRefGoogle Scholar
  21. 21.
    Baumgardner TL, Green KE, Reiss AL. A behavioral neurogenetics approach to developmental disabilities: gene-brain-behavior associations. Curr Opin Neurol 1994; 7(2): 172–8PubMedCrossRefGoogle Scholar
  22. 22.
    Lachiewicz AM, Spiridigliozzi GA, Gullion CM, et al. Aberrant behaviors of young boys with fragile X syndrome. Am J Ment Retard 1994; 98(5): 567–79PubMedGoogle Scholar
  23. 23.
    Kerby DS, Dawson BL. Autistic features, personality, and adaptive behavior in males with the fragile X syndrome and no autism. Am J Ment Retard 1994; 98(4): 455–62PubMedGoogle Scholar
  24. 24.
    Einfeld S, Tonge B, Turner G. Longitudinal course of behavioral and emotional problems in fragile X syndrome. Am J Med Genet 1999; 87(5): 436–9PubMedCrossRefGoogle Scholar
  25. 25.
    Carey WB. The difficult child. Pediatr Rev 1986; 8(2): 39–45PubMedCrossRefGoogle Scholar
  26. 26.
    Thomas A, Chess S, Birch H, et al. Temperament and personality. In: Kohnstamm G, Bates J, Rothbart M editors. Temperament in childhood. New York: John Wiley, 1989: 249–62Google Scholar
  27. 27.
    Carey WB, Jablow MM. Understanding your child’s temperament. New York: Macmillan, 1997Google Scholar
  28. 28.
    Hatton DD, Bailey Jr DB, Hargett-Beck MQ, et al. Behavioral style of young boys with fragile X syndrome. Dev Med Child Neurol 1999; 41(9): 625–32PubMedCrossRefGoogle Scholar
  29. 29.
    McDevitt SC, Carey WB. The measurement of temperament in 3-7 year old children. J Child Psychol Psychiatry 1978; 19(3): 245–53PubMedCrossRefGoogle Scholar
  30. 30.
    Thomas A, Chess S, Birch H, et al. Behavioral individuality in early childhood. New York: University Press, 1963Google Scholar
  31. 31.
    Carey W, McDevitt S. Coping with children’s temperament: a guide for professionals. New York: Basic Books, 1995Google Scholar
  32. 32.
    Carey WB, McDevitt SC, Baker D. Differentiating minimal brain dysfunction and temperament. Dev Med Child Neurol 1979; 21(6): 765–72PubMedCrossRefGoogle Scholar
  33. 33.
    DiLavore P. Maternal ratings of temperament in children with autism and children with Down syndrome [unpublished dissertation]. Chapel Hill (NC): University of North Carolina at Chapel Hill, 1991Google Scholar
  34. 34.
    Gunn P, Berry P. The temperament of Down’s syndrome toddlers and their siblings. J Child Psychol Psychiatry 1985; 26(6): 973–9PubMedCrossRefGoogle Scholar
  35. 35.
    Carey WB. Teaching parents about infant temperament. Pediatrics 1998; 102(5 Suppl. E): 1311–6PubMedGoogle Scholar
  36. 36.
    Rothbart M, Bates J. Temperament. In: Damon W, Eisenberg N, editors. Handbook of child psychology: social, emotional, and personality development. New York (NY): John Wiley, 1998Google Scholar
  37. 37.
    Wolff PH, Gardner J, Paccla J, et al. The greeting behavior of fragile X males. Am J Ment Retard 1989; 93(4): 406–11PubMedGoogle Scholar
  38. 38.
    Scharfenaker S, O’Connor R, Stackhouse T, et al. Anintegrated approach to intervention. In: Hagerman RJ, Hagerman PJ, editors. Fragile X syndrome: diagnosis, treatment and research. 3rd ed. Baltimore (MD): The Johns Hopkins University Press, 2002; 363: 427Google Scholar
  39. 39.
    Cohen IL. 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: 286–91CrossRefGoogle Scholar
  40. 40.
    Wells A, Clark DM, Salkovskis P, et al. Social phobia: the role of in-situation safety behaviors in maintaining anxiety and negative beliefs. Behav Ther 1995; 26: 153–61CrossRefGoogle Scholar
  41. 41.
    Belser RC, Sudhalter V. Arousal difficulties in males with Fragile X syndrome: a preliminary report. Dev Brain Dysfunct 1995; 8: 270–9Google Scholar
  42. 42.
    Miller LJ, McIntosh DN, McGrath J, et al. Electrodermal responses to sensory stimuli in individuals with fragile X syndrome: a preliminary report. Am J Med Genet 1999; 83(4): 268–79PubMedCrossRefGoogle Scholar
  43. 43.
    Boucsein W. Electrodermal activity. New York: Plenum Press, 1992Google Scholar
  44. 44.
    van Engeland H. The electrodermal orienting response to auditive stimuli in autistic children, normal children, mentally retarded children, and child psychiatric patients. J Autism Dev Disord 1984; 14(3): 261–79PubMedCrossRefGoogle Scholar
  45. 45.
    Hagerman RJ, Miller LJ, McGrath-Clarke J, et al. Influence of stimulants on electrodermal studies in Fragile X syndrome. Microsc Res Tech 2002; 57(3): 168–73PubMedCrossRefGoogle Scholar
  46. 46.
    Hagerman RJ, Murphy MA, Wittenberger MD. A controlled trial of stimulant medication in children with the fragile X syndrome. Am J Med Genet 1988; 30(1–2): 377–92PubMedCrossRefGoogle Scholar
  47. 47.
    Hunt RD, Minderaa RB, Cohen DJ. Clonidine benefits children with attention deficit disorder and hyperactivity: report of a double-blind placebo-crossover therapeutic trial. J Am Acad Child Psychiatry 1985; 24(5): 617–29PubMedCrossRefGoogle Scholar
  48. 48.
    Abitbol M, Menini C, Delezoide A, et al. Nucleus basalis magnocellularis and hippocampus are the major sites of FMR-1 expression in the human fetal brain. Nat Genet 1993; 4(2): 147–53PubMedCrossRefGoogle Scholar
  49. 49.
    Beardslee WR, Versage EM, Gladstone TRG. Children of affectively ill parents: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry 1998; 37: 1134–41PubMedCrossRefGoogle Scholar
  50. 50.
    Smalley SL, McCracken J, Tanguay P. Autism, affective disorders, and social phobia. Am J Med Genet 1995; 60: 19–26PubMedCrossRefGoogle Scholar
  51. 51.
    Mazzocco MMM, Baumgardner T, Freund LS, et al. Social functioning among girls with fragile X or Turner syndrome and their sisters. J Autism and Dev Disord 1998; 28(6): 509–17CrossRefGoogle Scholar
  52. 52.
    Hessl D, Dyer-Friedman J, Glaser B, et al. The influence of environmental and genetic factors on behavior problems and autistic symptoms in boys and girls with fragile X syndrome. Pediatrics 2001; 108(5): 1–9CrossRefGoogle Scholar
  53. 53.
    Tsiouris JA, Cohen IL, Patti PJ, et al. Treatment of the previously undiagnosed psychiatric disorders in persons with developmental disabilities decreased or eliminated self-injurious behavior. J Clin Psychiatry 2003; 64(9): 1081–90PubMedCrossRefGoogle Scholar
  54. 54.
    Howard-Peebles PN, Stoddard GR, Miss MG. Familial X-linked mental retardation, verbal disability and marker X chromosome. Am J Hum Genet 1979; 31: 214–22PubMedGoogle Scholar
  55. 55.
    Spinelli M, deOliveira Rocha AC, Giacheti CM, et al. Word-finding difficulties, verbal paraphasias, and verbal dyspraxia in ten individuals with fragile X syndrome. Am J Med Genet 1995; 60: 39–43PubMedCrossRefGoogle Scholar
  56. 56.
    Sudhalter V, Scarborough HS, Cohen IL. Syntactic delay and pragmatic deviance in the language of fragile X males. Am J Med Genet 1991; 38: 493–7PubMedCrossRefGoogle Scholar
  57. 57.
    Sudhalter V, Cohen IL, Silverman W, et al. Conversational analyses of males with fragile X, Down syndrome and autism: comparison of the emergence of deviant language. Am J Ment Retard 1990; 94: 431–41PubMedGoogle Scholar
  58. 58.
    Sudhalter V, Belser RC. Conversational characteristics of children with fragile X syndrome: tangential language. Am J Ment Retard 2001; 106(5): 389–00PubMedCrossRefGoogle Scholar
  59. 59.
    Hagerman RJ, Jackson AW, Levitas A, et al. An analysis of autism in 50 males with fragile X syndrome. Am J Med Genet 1986; 23: 359–70PubMedCrossRefGoogle Scholar
  60. 60.
    Turk J, Cornish K. Face recognition and emotion perception in boys with fragile-X syndrome. J Intellect Disabil Res 1998; 42(6): 490–9PubMedCrossRefGoogle Scholar
  61. 61.
    Hobson RP. The autistic child’s appraisal of expressions of emotion: a further study. J Child Psychol Psychiatry 1986; 27: 671–80PubMedCrossRefGoogle Scholar
  62. 62.
    Davies S, Bishop D, Manstead SR, et al. Face perception in children with autism and Asperger’s syndrome. J Child Psychol Psychiatry 1994; 35: 1033–57PubMedCrossRefGoogle Scholar
  63. 63.
    Hatton DD, Hooper SR, Bailey DB, et al. Problem behavior in boys with fragile X syndrome. Am J Med Genet 2002; 108: 105–16PubMedCrossRefGoogle Scholar
  64. 64.
    Cohen IL, Sudhalter V, Pfadt A, et al. Why are autism and the fragile X syndrome associated? Am J Hum Genet 1991; 48: 195–202PubMedGoogle Scholar
  65. 65.
    Brown WT, Jenkins EC, Friedman E, et al. Autism is associated with the fragile X syndrome. J Autism Dev Disabilities 1982; 12: 303–7CrossRefGoogle Scholar
  66. 66.
    Brown WT, Jenkins EC, Cohen IL, et al. Fragile X and autism: a multicenter survey. Am J Med Genet 1986; 23: 341–52PubMedCrossRefGoogle Scholar
  67. 67.
    Dykens EM, Volkmar FR. Medical conditions associated with autism. In: Cohen DJ, Volkmar FR, editors. Handbook of autism and pervasive developmental disorder. 2nd ed. New York: J. Wiley, 1997: 388–407Google Scholar
  68. 68.
    Bailey A, Bolton P, Butler L, et al. Prevalence of the fragile X anomaly amoungst autistic twins and singletons. J Child Psychol Psychiatry 1993; 34: 673–88PubMedCrossRefGoogle Scholar
  69. 69.
    Bailey DB, Hatton DD, Skinner M, et al. Autistic behavior, FMR1 protein and developmental trajectories in young males with fragile X syndrome. J Autism Dev Disord 2001; 31: 165–74PubMedCrossRefGoogle Scholar
  70. 70.
    Lamb JA, Parr JR, Bailey AJ, et al. Autism: in search of susceptibility genes. Neuromolecular Med 2002; 2: 11–28PubMedCrossRefGoogle Scholar
  71. 71.
    Feinstein C, Reiss AL. Autism: the point of view from fragile X studies. J Autism Dev Disord 1998; 28: 393–405PubMedCrossRefGoogle Scholar
  72. 72.
    Rogers SJ, Wehner DE, 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 Dec; 22(6): 409–17PubMedCrossRefGoogle Scholar
  73. 73.
    Cohen IL, Liu X, Schutz C, et al. Association of autism severity with an MAOA functional polymorphism. Clin Genet 2003; 64: 190–7PubMedCrossRefGoogle Scholar
  74. 74.
    Amaria RN, Billeisen LL, Hagerman RJ. Medication use in fragile X syndrome. Ment Health Aspects Dev Disabil 2001; 4: 143–7Google Scholar
  75. 75.
    Hagerman RJ, Fulton MJ, Leaman A, et al. A survey of fluoxetine therapy in fragile X syndrome. Dev Brain Dysfunct 1994; 7: 155–64Google Scholar
  76. 76.
    Hagerman RJ, Hills J, Scharfenaker S, et al. Fragile X syndrome and selective mutism. Am J Med Genet 1999; 83(4): 313–7PubMedCrossRefGoogle Scholar
  77. 77.
    Rojahn J, Borthwick-Duffy SA, Jacobson JW. The association between psychiatric diagnoses and severe behavior problems in mental retardation. Ann Clin Psychiatry 1993; 5: 163–70PubMedCrossRefGoogle Scholar
  78. 78.
    Tsiouris JA, Mann R, Patti PJ, et al. Challenging behaviours should not be considered as depressive equivalents in individuals with intellectual disability. J Intellect Disabil Res 2003 Jan; 47(1): 14–21PubMedCrossRefGoogle Scholar
  79. 79.
    Sutherland GR. Fragile sites on human chromosomes: demonstration of their dependence on the type of tissue culture medium. Science 1977; 197(4300): 265–6PubMedCrossRefGoogle Scholar
  80. 80.
    Greenblatt JM, Huffman LC, Reiss AL. Folic acid in neurodevelopment and child psychiatry. Prog Neuropsychopharmacol Biol Psychiatry 1994; 18: 647–60PubMedCrossRefGoogle Scholar
  81. 81.
    Lejeune J. Is the fragile X syndrome amenable to treatment? Lancet 1982; I(8266): 273–4CrossRefGoogle Scholar
  82. 82.
    Lejeune J, Rethore MO, de Blois MC, et al. Trial of folic acid treatment in fragile X syndrome [in French]. Ann Genet 1984; 27(4): 230–2PubMedGoogle Scholar
  83. 83.
    Hagerman RJ, Jackson AW, Levitas A, et al. Oral folic acid versus placebo in the treatment of males with the fragile X syndrome. Am J Med Genet 1986; 23: 241–62PubMedCrossRefGoogle Scholar
  84. 84.
    Hagerman RJ. Medical follow-up and pharmacotherapy. In: Hagerman RJ, Hagerman PJ, editors. Fragile X syndrome: diagnosis, treatment and research. 3rd ed. Baltimore (MD): Johns Hopkins University Press, 2002: 287–338Google Scholar
  85. 85.
    Torrioli MG, Vernacotola S, Mariotti P, et al. Double-blind, placebo-controlled study of L-acetylcarnitine for the treatment of hyperactive behavior in fragile X syndrome. Am J Med Genet 1999; 87(4): 366–8PubMedCrossRefGoogle Scholar
  86. 86.
    Aman MG, Singh NN. Methylphenidate in severely retarded residents and the clinical significance of stereotypic behavior. Appl Res Ment Retard 1982; 3(4): 345–58PubMedCrossRefGoogle Scholar
  87. 87.
    Kratochvil CJ, Heiligenstein JH, Dittmann R, et al. Atomoxetine and methylphenidate treatment in children with ADHD: a prospective, randomized, open-label trial. J Am Acad Child Adolesc Psychiatry 2002; 41(7): 776–84PubMedCrossRefGoogle Scholar
  88. 88.
    Hilton DK, Martin CA, Heffron WM, et al. Imipramine treatment of ADHD in a fragile X child. J Am Acad Child Adolesc Psychiatry 1991; 30: 831–4PubMedGoogle Scholar
  89. 89.
    Hellings JC, Gaffney GR. A trigger for Tourette’s syndrome. J Am Acad Child Adolesc Psychiatry 1992; 31(2): 371–2PubMedCrossRefGoogle Scholar
  90. 90.
    Dunner KL, Zisook S, Billow AA, et al. A prospective safety surveillance study for bupropion sustained release in the treatment of depression. J Clin Psychiatry 1998; 59: 366–74PubMedCrossRefGoogle Scholar
  91. 91.
    Berry-Kravis E. Clinical trial of a new medication in adults with fragile X [online]. Available from URL: [Accessed 2004 Jul 30]
  92. 92.
    Steiner H, Saxena K, Chang K. Psychopharmacologic strategies for the treatment of aggression in juveniles. CNS Spectrums 2003; 8(4): 298–308PubMedGoogle Scholar
  93. 93.
    Bear MF, Huber KM, Warren ST. The mGluR theory of fragile X mental retardation. Trends Neurosci 2004; Jul; 27(7): 370–7.PubMedCrossRefGoogle Scholar
  94. 94.
    Coccaro EF, Harvey PD, Kupsaw-Lawrence E, et al. Development of neuropharmacologically based behavioral assessments of impulsive aggressive behavior. J Neuropsychiatry Clin Neurosci 1991; 3(2): S44–51PubMedGoogle Scholar
  95. 95.
    Coccaro EF. Central serotonin and impulsive aggression. Br J Psychiatry Suppl 1989; 8: 52–62PubMedGoogle Scholar
  96. 96.
    Hagerman RJ, Bregman JD, Tirosh E. Clonidine. In: Reis S, Aman MG, editors. Psychotropic medication and developmental disabilities: the international consensus handbook. Columbus (OH): Ohio State University Nisonger Center, 1998: 259–69Google Scholar
  97. 97.
    Hagerman RJ, Riddle JE, Roberts LS, et al. A survey of the efficacy of clonidine in fragile X syndrome. Dev Brain Dysfunct 1995; 8: 336–44Google Scholar
  98. 98.
    Tyrer PJ, Lader MH. Response to propranolol and diazepam in somatic and psychic anxiety. BMJ 1974; 2(909): 14–6PubMedCrossRefGoogle Scholar
  99. 99.
    Williams EM, Campbell TJ. The effects of nadolol on various cardiac tissues in normoxia, and on atrial muscle in simulated ischaemia. Eur J Pharmacol 1982; 83(3–4): 161–9PubMedCrossRefGoogle Scholar
  100. 100.
    Greendyke RM, Kanter DR. Therapeutic effects of pindolol on behavioral disturbances associated with organic brain disease: a double-blind study. J Clin Psychiatry 1986; 47(8): 423–6PubMedGoogle Scholar
  101. 101.
    Reudrich SL, Grush L, Wilson J. Beta adrenergic blocking medications for aggressive or self-injurious mentally retarded persons. Am J Ment Retard 1990; 95: 110–9Google Scholar
  102. 102.
    Cohen IL, Tsiouris JA, Pfadt A. Effects of long-acting propranolol on agonistic and stereotyped behaviors in a man with pervasive developmental disorder and fragile X syndrome: a double-blind, placebo-controlled study. J Clin Psychopharmacol 1991; 11(6): 398–9PubMedCrossRefGoogle Scholar
  103. 103.
    Hagerman RJ. Medical follow-up and pharmacotherapy. In: Hagerman RJ, Cronister A, editors. Fragile X syndrome: diagnosis, treatment, and research. 2nd ed. Baltimore (MD): Johns Hopkins University Press, 1996: 283–331Google Scholar
  104. 104.
    Tsiouris JA. Diagnosis of depression in people with severe/profound intellectual disability. J Intellect Disabil Res 2001; 45(Pt 2): 115–20PubMedCrossRefGoogle Scholar
  105. 105.
    Szymanski LS, King B, Goldberg B, et al. Diagnosis of mental disorders in people with mental retardation. In: Reiss S, Aman MG, editors. Psychotropic medications and developmental disabilities: the international consensus handbook. Columbus (OH): Ohio State University Nisonger Center, 1998: 3–17Google Scholar
  106. 106.
    Backes M, Genc B, Schreck J, et al. Cognitive and behavioral profile of fragile X boys: correlations to molecular data. Am J Med Genet 2000; 95(2): 150–6PubMedCrossRefGoogle Scholar
  107. 107.
    Reilly JG, Avis SA, Ferrier IN, et al. QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet 2000; 355: 1048–52PubMedCrossRefGoogle Scholar
  108. 108.
    Hennessy S, Bilker WB, Knauss JS, et al. Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data. BMJ 2002 Nov; 325: 1070–2PubMedCrossRefGoogle Scholar
  109. 109.
    Davis M, Whalen PJ. The amygdala: vigilance and emotion. Mol Psychiatry 2001; 6(1): 13–34PubMedCrossRefGoogle Scholar
  110. 110.
    Davis M. The role of the amygdala in fear and anxiety. Annu Rev Neurosci 1992; 15: 353–75PubMedCrossRefGoogle Scholar
  111. 111.
    Paradee W, Melikian HE, Rasmussen DL, et al. Fragile X mouse: strain effects of knockout phenotype and evidence suggesting deficient amygdala function. Neuroscience 1999; 94(1): 185–92PubMedCrossRefGoogle Scholar
  112. 112.
    Tamm L, Menon V, Johnston CK, et al. fMRI study of cognitive interference processing in females with fragile X syndrome. J Cogn Neurosci 2002 Feb 15; 14(2): 160–71PubMedCrossRefGoogle Scholar
  113. 113.
    Yang TT, Menon V, Eliez S, et al. Amygdalar activation associated with positive and negative facial expressions. Neuroreport 2002 Oct 7; 13(14): 1737–41PubMedCrossRefGoogle Scholar
  114. 114.
    Musumeci SA, Bosco P, Calabrese G, et al. Audiogenic seizures susceptibility in transgenic mice with fragile X syndrome. Epilepsia 2000; 41(1): 19–23PubMedCrossRefGoogle Scholar
  115. 115.
    Huber KM, Gallagher SM, Warren ST, et al. Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc Natl Acad Sci U S A 2002; 99(11): 7746–50PubMedCrossRefGoogle Scholar
  116. 116.
    Kent JM, Mathew SJ, Gorman JM. Molecular targets in the treatment of anxiety. Biol Psychiatry 2002; 52: 1008–30PubMedCrossRefGoogle Scholar
  117. 117.
    Lainhart JE. Psychiatric problems in individuals with autism, their parents and siblings. Int Rev Psychiatry 1999; 11: 278–98CrossRefGoogle Scholar
  118. 118.
    McDougle CJ, Posey DJ. Autistic and other pervasive developmental disorders. In: Martin A, Scahill L, Charney DS, et al., editors. Pediatric psychopharmacology: principles and practice. New York: Oxford University Press, 2002Google Scholar
  119. 119.
    Aman MG, Langworthy KS. Pharmacotherapy for hyperactivity in children with autism and other pervasive developmental disorders. J Autism Dev Disord 2000; 30(5): 451–9PubMedCrossRefGoogle Scholar
  120. 120.
    King BH. Pharmacological treatment of mood disturbances, aggression, and self-injury in persons with pervasive developmental disorders. J Autism Dev Disord 2000; 30(5): 439–45PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.IBR-George A. Jervis ClinicNew York State Institute for Basic Research in Developmental DisabilitiesStaten IslandUSA
  2. 2.Department of Human GeneticsNew York State Institute for Basic Research in Developmental DisabilitiesStaten IslandUSA

Personalised recommendations