Psychometric Study of the Aberrant Behavior Checklist in Fragile X Syndrome and Implications for Targeted Treatment

Sansone, Stephanie M.; Widaman, Keith F.; Hall, Scott S.; Reiss, Allan L.; Lightbody, Amy A.; Kaufmann, Walter E.; Berry‐Kravis, Elizabeth; Lachiewicz, Ave M.; Brown, Edward A.; Hessl, David

doi:10.1007/s10803-011-1370-2

Cited by 152 publications

(159 citation statements)

References 81 publications

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“…A majority of the improvement measures were based on parent or caregiver response,42,66 which is subjective. More objective outcome measures are needed, not only for GABAergic medications, but for all clinical trials that focus on neurodevelopmental indications.…”

Section: Resultsmentioning

confidence: 99%

“…The primary outcome measure, the Aberrant Behavior Checklist-Community Edition, a 58-item behavioral questionnaire, did not show reduction in any of the subscales compared to placebo42 and, due to resource limitations, Seaside Therapeutics had to terminate its arbaclofen program 65. However, a post hoc analysis saw a full study improvement on the Aberrant Behavior Checklist Social Avoidance subscale, which was an algorithm developed specifically to assess behavioral function in patients with FXS 66. In addition, a subgroup of 27 patients with more severe social impairment treated with arbaclofen showed improvement on all global measures, as well as on the Vineland Socialization subscale, which is a semi-structured parent interview that assesses adaptive behavior.…”

Section: Gabaergic Treatmentsmentioning

confidence: 99%

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Modulation of the GABAergic pathway for the treatment of fragile X syndrome

Lozano¹,

Hare²,

Hagerman³

2014

NDT

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Fragile X syndrome (FXS) is the most common genetic cause of intellectual disability and the most common single-gene cause of autism. It is caused by mutations on the fragile X mental retardation gene (FMR1) and lack of fragile X mental retardation protein, which in turn, leads to decreased inhibition of translation of many synaptic proteins. The metabotropic glutamate receptor (mGluR) hypothesis states that the neurological deficits in individuals with FXS are due mainly to downstream consequences of overstimulation of the mGluR pathway. The main efforts have focused on mGluR5 targeted treatments; however, investigation on the gamma-aminobutyric acid (GABA) system and its potential as a targeted treatment is less emphasized. The fragile X mouse models (Fmr1-knock out) show decreased GABA subunit receptors, decreased synthesis of GABA, increased catabolism of GABA, and overall decreased GABAergic input in many regions of the brain. Consequences of the reduced GABAergic input in FXS include oversensitivity to sensory stimuli, seizures, and anxiety. Deficits in the GABA receptors in different regions of the brain are associated with behavioral and attentional processing deficits linked to anxiety and autistic behaviors. The understanding of the neurobiology of FXS has led to the development of targeted treatments for the core behavioral features of FXS, which include social deficits, inattention, and anxiety. These symptoms are also observed in individuals with autism and other neurodevelopmental disorders, therefore the targeted treatments for FXS are leading the way in the treatment of other neurodevelopmental syndromes and autism. The GABAergic system in FXS represents a target for new treatments. Herein, we discuss the animal and human trials of GABAergic treatment in FXS. Arbaclofen and ganaxolone have been used in individuals with FXS. Other potential GABAergic treatments, such as riluzole, gaboxadol, tiagabine, and vigabatrin, will be also discussed. Further studies are needed to determine the safety and efficacy of GABAergic treatments for FXS.

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Section: Resultsmentioning

confidence: 99%

Section: Gabaergic Treatmentsmentioning

confidence: 99%

Modulation of the GABAergic pathway for the treatment of fragile X syndrome

Lozano¹,

Hare²,

Hagerman³

2014

NDT

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“…Our group recently completed a large psychometric study of the ABC in FXS, yielding a somewhat altered factor structure specific to FXS including 6 validated subscales: irritability, hyperactivity, socially unresponsive/lethargic behavior, social avoidance, stereotypy and inappropriate speech (Sansone et al 2012). The Behavioral Assessment for Children, second edition (BASC-2) was also collected (Reynolds and Kamphaus 2004).…”

Section: Methodsmentioning

confidence: 99%

Emotion Potentiated Startle in Fragile X Syndrome

Ballinger

Cordeiro

Chavez

et al. 2014

J Autism Dev Disord

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Social avoidance and anxiety are prevalent in fragile X syndrome (FXS) and are potentially mediated by the amygdala, a brain region critical for social behavior. Unfortunately, fMRI investigation of the amygdala in FXS is limited by the difficulties experienced by intellectually impaired and anxious participants. We investigated the relationship between social avoidance and emotion-potentiated startle, a probe of amygdala activation, in children and adolescents with FXS, developmental disability without FXS (DD), and typical development. Individuals with FXS or DD demonstrated significantly reduced potentiation to fearful faces than a typically developing control group (p<.05). However, among individuals with FXS, social avoidance correlated positively with fearful-face potentiation (p<.05). This suggests that general intellectual disability blunts amygdalar response, but differential amygdala responsiveness to social stimuli contributes to phenotypic variability among individuals with FXS.

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“…Recently, a 12-week open label trial of lovastatin in patients with FXS was completed (75); sixteen participants were initially enrolled (mean age = 18 ± 5 years), and 15 subjects finished the study. Results showed significant benefit on the ABC-C after 4 weeks of treatment, and further improvements were observed with continued use throughout the study specifically in areas of hyperactivity, lethargy, social avoidance, and stereotypy as determined by the ABC-C FX (41). Participants also experienced significant improvements in communication, daily living skills, and coping skills on the VABS.…”

Section: Lovastatinmentioning

confidence: 85%