Prepulse inhibition in fragile X syndrome: feasibility, reliability, and implications for treatment.
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.
Hessl
David
D
Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute, University of California-Davis, Medical Center, Sacramento, California 95817, USA. david.hessl@ucdmc.ucdavis.edu
Berry-Kravis
Elizabeth
E
Cordeiro
Lisa
L
Yuhas
Jennifer
J
Ornitz
Edward M
EM
Campbell
Aaron
A
Chruscinski
Elizabeth
E
Hervey
Crystal
C
Long
James M
JM
Hagerman
Randi J
RJ
D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology / Q000503:physiopathology; D016022:Case-Control Studies; D002986:Clinical Trials as Topic; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011930:Reaction Time / Q000502:physiology; D013216:Reflex, Startle; D015203:Reproducibility of Results; D055139:Sensory Gating; D055815:Young Adult
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