DMD – BIOMARKERS & OUTCOME MEASURES: P.133 Increased physiological responses to threat in Duchenne muscular dystrophy: A potential CNS outcome measure

Abstract

Dystrophin is expressed in brain as well as muscle, and its loss in Duchenne muscular dystrophy (DMD) causes CNS disturbance in addition to muscle pathology. A DMD mouse model (mdx) exhibits exaggerated fear responses to threat, which normalise with postnatal dystrophin-restoration therapies. To investigate if abnormal fear responses are present in humans with DMD, we tested 31 DMD and 25 control males aged 7-12 years using a fear conditioning task. During the acquisition phase, participants were presented with trials of two neutral visual stimuli: one ‘safe’ stimulus presented alone; one paired with an aversive noise ‘threat’ to enable fear conditioning.