Prepulse inhibition in fragile X syndrome: Feasibility, reliability, and implications for treatment

David R Hessl, Elizabeth Berry-Kravis, Lisa Cordeiro, Jennifer Yuhas, Edward M. Ornitz, Aaron Campbell, Elizabeth Chruscinski, Crystal Hervey, James M. Long, Randi J Hagerman

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Pharmacological rescue of behavioral, cognitive and synaptic abnormalities in the animal models of fragile X syndrome (FXS) has prompted the initiation of clinical trials of targeted treatments in humans with this condition. Objective, well-validated outcome measures that are reflective of FXS deficits and can be modeled similarly in animal and human studies are urgently needed. A protocol measuring prepulse inhibition (PPI) of the startle reflex, including measures of test-retest stability, was evaluated in 61 individuals with the fragile X full mutation (40 males and 21 females; 19.18 ± 7.18 years) and 63 age-matched normal controls (35 males and 28 females; 20.83 ± 6.96 years) across two laboratory sites with identical equipment and protocols. Relative to controls, the fragile X group had PPI impairment of 26%, 22%, and 28% for 60, 120, and 240 ms prepulse interval trial types, respectively, P = 0.000002. PPI test-retest reliability in 29 of the participants was excellent for the 120 ms prepulse interval trials (intraclass correlations: FXS, 0.85; controls, 0.88, 0.89 overall). This study demonstrates the feasibility and reliability of PPI measurement in a developmentally disabled population and highlights its potential as an outcome measure to test the efficacy of targeted neurotherapeutic agents.

Original languageEnglish (US)
Pages (from-to)545-553
Number of pages9
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume150
Issue number4
DOIs
StatePublished - Jun 5 2009

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Fragile X Syndrome
Startle Reflex
Outcome Assessment (Health Care)
Feasibility Studies
Therapeutics
Reproducibility of Results
Animal Models
Clinical Trials
Pharmacology
Equipment and Supplies
Mutation
Prepulse Inhibition
Population

Keywords

  • FMR1 gene
  • mGlur5
  • PPI
  • Prepulse inhibition
  • Sensorimotor gating

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Prepulse inhibition in fragile X syndrome : Feasibility, reliability, and implications for treatment. / Hessl, David R; Berry-Kravis, Elizabeth; Cordeiro, Lisa; Yuhas, Jennifer; Ornitz, Edward M.; Campbell, Aaron; Chruscinski, Elizabeth; Hervey, Crystal; Long, James M.; Hagerman, Randi J.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 150, No. 4, 05.06.2009, p. 545-553.

Research output: Contribution to journalArticle

Hessl, David R ; Berry-Kravis, Elizabeth ; Cordeiro, Lisa ; Yuhas, Jennifer ; Ornitz, Edward M. ; Campbell, Aaron ; Chruscinski, Elizabeth ; Hervey, Crystal ; Long, James M. ; Hagerman, Randi J. / Prepulse inhibition in fragile X syndrome : Feasibility, reliability, and implications for treatment. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2009 ; Vol. 150, No. 4. pp. 545-553.
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