Dataset Information

Effects of mavoglurant on visual attention and pupil reactivity while viewing photographs of faces in Fragile X Syndrome.

ABSTRACT: BACKGROUND:Numerous preclinical studies have supported the theory that enhanced activation of mGluR5 signaling, due to the absence or reduction of the FMR1 protein, contributes to cognitive and behavioral deficits in patients with fragile X syndrome (FXS). However multiple phase 2 controlled trials in patients with FXS have failed to demonstrate efficacy of compounds that negatively modulate mGluR5, including two phase 2b randomized controlled trials (RCT) of mavoglurant (AFQ056, Novartis Pharma AG), when the primary measures of interest were behavioral ratings. This has cast some doubt onto the translation of the mGluR5 theory from animal models to humans with the disorder. METHODS:We evaluated social gaze behavior-a key phenotypic feature of the disorder-and sympathetic nervous system influence on pupil size using a previously-validated eye tracking paradigm as a biobehavioral probe, in 57 adolescent or adult patients with FXS at baseline and following three months of blinded treatment with one of three doses of mavoglurant or placebo, within the context of the AFQ056 RCTs. RESULTS:Patients with FXS treated with mavoglurant demonstrated increased total absolute looking time and number of fixations to the eye region while viewing human faces relative to baseline, and compared to those treated with placebo. In addition, patients had greater pupil reactivity to faces relative to baseline following mavoglurant treatment compared to placebo. DISCUSSION:The study shows that negative modulation of mGluR5 activity improves eye gaze behavior and alters sympathetically-driven reactivity to faces in patients with FXS, providing preliminary evidence of this drug's impact on behavior in humans with the disorder.

SUBMITTER: Hessl D

PROVIDER: S-EPMC6336311 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Effects of mavoglurant on visual attention and pupil reactivity while viewing photographs of faces in Fragile X Syndrome.

Hessl David D Harvey Danielle D Sansone Stephanie S Crestodina Crystal C Chin Jamie J Joshi Reshma R Hagerman Randi J RJ Berry-Kravis Elizabeth E

PloS one 20190117 1

<h4>Background</h4>Numerous preclinical studies have supported the theory that enhanced activation of mGluR5 signaling, due to the absence or reduction of the FMR1 protein, contributes to cognitive and behavioral deficits in patients with fragile X syndrome (FXS). However multiple phase 2 controlled trials in patients with FXS have failed to demonstrate efficacy of compounds that negatively modulate mGluR5, including two phase 2b randomized controlled trials (RCT) of mavoglurant (AFQ056, Novarti ...[more]

PMID: 30653533

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Project description:Diminished attention to socially relevant information appears to be an early emerging risk factor associated with autism spectrum disorders (ASD). However, inconsistencies across studies suggest that atypicalities in visual social attention in infants at high-risk for ASD during the first postnatal year may be subtle and more apparent under certain contexts. Here we explore factors that may moderate developmental trajectories in attention to faces, including the social complexity of the dynamic visual stimuli used to measure visual social attention and the early social environment of the infant as indexed by parental affectedness of ASD-related traits. Across infants at both high (HR) and low risk for ASD, attention to faces increased during the first postnatal year, with overall greater attention being allocated to schematic faces in the simpler video stimulus. Moreover, greater parental affectedness of ASD-related traits was associated with reduced developmental gains in attention to faces. For HR infants, greater attention to faces was positively associated with social communicative competence, including better joint attention skills and lower social impairments. Altogether, our findings highlight the importance of considering developmental level when selecting stimuli to longitudinally examine visual social attention, and the clinical relevance of including measures of infant's social environment in understanding early markers of ASD risk. Autism Res 2019, 12: 445-457 © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Attention to faces is an important means for infants to learn about the social world. The complexity of the social scene and an infant's early social environment both affect the amount of time infants at high- and low-risk for ASD look at faces during the first postnatal year. For infants at high-risk for ASD, greater attention to faces was associated with better social skills. Understanding an infant's social environment may have a positive impact on social communicative development.

Dataset Information

Effects of mavoglurant on visual attention and pupil reactivity while viewing photographs of faces in Fragile X Syndrome.

Publications

Effects of mavoglurant on visual attention and pupil reactivity while viewing photographs of faces in Fragile X Syndrome.

Similar Datasets

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