A controlled trial of stimulant medication in children with the fragile X syndrome

Hagerman, Randi J.; Murphy, Mary; Wittenberger, Michael D.

doi:10.1002/ajmg.1320300138

Cited by 150 publications

(82 citation statements)

References 27 publications

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“…Psychostimulants are the most often prescribed psychoactive medication to treat FXS [730], with initial randomized controlled trial data of response to methylphenidate and dextroamphetamine suggesting moderate response rates on attention and social skills [731]. Preliminary studies of aripiprazole in FXS have also found evidence for an improvement in clinical symptoms and irritability [732,733].…”

Section: Reviewmentioning

confidence: 99%

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Dichter

Damiano

Allen

2012

J Neurodevelop Disord

253

207

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This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

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Section: Reviewmentioning

confidence: 99%

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Dichter

Damiano

Allen

2012

J Neurodevelop Disord

253

207

View full text Add to dashboard Cite

show abstract

“…Parents and professionals often report that challenging behaviors are their greatest concern regarding their child with FXS [Hagerman, 1996b;Hatton et al, 2000]. Perhaps one of the most striking indicators of these problems is the extensive use of medications with FXS children, sometimes at very young ages [Tranfaglia, 1995;Hagerman, 1996a].In estimating the effectiveness of stimulants, one study reported that attention and sociability were improved in boys with FXS on a trial of methylphenidate [Hagerman et al, 1988]. Interestingly, the effectiveness of stimulants may be related to intellectual ability and, more speci®cally, may not be effective in children with severe mental retardation.…”

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confidence: 97%

Problem behavior in boys with fragile X syndrome

et al. 2002

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This study examines problem behavior over time in 59 boys with fragile X syndrome (FXS), aged 4-12 years, using the Child Behavior Checklist (CBCL). Approximately 49% of the boys scored within the borderline or clinical range on total problem behavior, while 56-57% scored in the borderline or clinical range on the attention and thought problems subscales, and 26% scored in this range on the social problems subscale. With a mean of 2.5 assessments per child, behavior problems were stable during the 3-year period of study. Total problem behavior was higher for children who displayed autistic behavior, were rated as low in adaptability, had mothers with higher maternal education levels, and were on medication. Mothers with more education also rated their children as having more attention, thought, and total problems. Children taking medication differed from boys who were not taking medication on social problems, but not on attention and thought problems. Low adaptability and more autistic characteristics predicted thought problems.

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“…While an early controlled trial of stimulant medication for ADHD symptoms in fragile X children showed modest benefit [Hagerman et al, 1988], the study suffered from a number of methodological shortcomings, including a small number of subjects, the use of two different study drugs, and a very brief duration of treatment. Even with a brief exposure to the active drug, significant psychiatric side effects were seen in some subjects.…”

Section: Attention Deficit and Hyperactivitymentioning

confidence: 99%

The Psychiatric Presentation of Fragile X: Evolution of the Diagnosis and Treatment of the Psychiatric Comorbidities of Fragile X Syndrome

Tranfaglia¹

2011

Dev Neurosci

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Fragile X syndrome (FXS) is the leading inherited cause of mental retardation and autism spectrum disorders worldwide. It presents with a distinct behavioral phenotype which overlaps significantly with that of autism. Unlike autism and most common psychiatric disorders, the neurobiology of fragile X is relatively well understood. Lack of the fragile X mental retardation protein causes dysregulation of synaptically driven protein synthesis, which in turn causes global disruption of synaptic plasticity. Thus, FXS can be considered a disorder of synaptic plasticity, and a developmental disorder in the purest sense: mutation of the FMR1 (fragile X mental retardation 1) gene results in abnormal synaptic development in response to experience. Accumulation of this abnormal synaptic development, over time, leads to a characteristic and surprisingly consistent behavioral phenotype of attention deficit, hyperactivity, impulsivity, multiple anxiety symptoms, repetitive/perseverative/stereotypic behaviors, unstable affect, aggression, and self-injurious behavior. Many features of the behavioral and psychiatric phenotype of FXS follow a developmental course, waxing and waning over the life span. In most cases, symptoms present as a mixed clinical picture, not fitting established diagnostic categories. There have been many clinical trials in fragile X subjects, but no placebo-controlled trials of adequate size or methodology utilizing the most commonly prescribed psychiatric medications. However, large and well-designed trials of investigational agents which target the underlying pathology of FXS have recently been completed or are under way. While the literature offers little guidance to the clinician treating patients with FXS today, potentially disease-modifying treatments may be available in the near future.

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A controlled trial of stimulant medication in children with the fragile X syndrome

Cited by 150 publications

References 27 publications

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Problem behavior in boys with fragile X syndrome

The Psychiatric Presentation of Fragile X: Evolution of the Diagnosis and Treatment of the Psychiatric Comorbidities of Fragile X Syndrome

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