Review of Autism Profiles and Response to Sertraline in Fragile X Syndrome-Associated Autism vs. Non-syndromic Autism; Next Steps for Targeted Treatment.

Akash Rajaratnam,Ignacio Cortina Petrasic,Andrea Schneider,Hazel Maridith Barlahan Biag,Randi Jenssen Hagerman,Laura Axelrod Potter

doi:10.3389/fneur.2020.581429

Akash Rajaratnam, Ignacio Cortina Petrasic + Show 4 more

Open Access

https://doi.org/10.3389/fneur.2020.581429

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Abstract

Given significant genetic, molecular, and phenotypic overlaps, researchers have begun to investigate whether targeted treatments for Fragile X Syndrome (FXS) could also be beneficial for patients with Autism Spectrum Disorder (ASD). For example, low-dose sertraline, an SSRI, was used in two recent controlled trials in children with FXS and ASD. The first trial recruited 52 children with FXS, 32 of which were also diagnosed with ASD; the second trial recruited 58 children with non-syndromic ASD. One focus of the present study is to compare the response to sertraline between the FXS-associated ASD and non-syndromic ASD groups. Another focus is to compare baseline ASD-related characteristics between the groups and review these differences within the context of recent literature comparing these populations. Our comparison showed more severe ASD profiles in children with non-syndromic ASD vs. FXS-associated ASD. Regarding response to sertraline, the FXS-ASD group displayed significant improvements in language development, while the non-syndromic group did not show any significant improvements. One possible explanation for this differential response is the distinct anxiety profiles that are seen in these two groups. The heightened anxiety phenotype seen in those with FXS-ASD may have led to a greater relief of anxiety symptoms with sertraline compared to those with non-syndromic ASD; this, in turn, could have led to measurably greater developmental gains. Further research is required to solidify this connection between anxiety relief and developmental gains in these populations.

Highlights

Autism spectrum disorder (ASD) is a behaviorally defined neurodevelopmental disorder that is characterized by impaired social and language development, repetitive behaviors, and restricted interests, as well as hyper or hypo-reactivity to sensory inputs
Our results showed that ADOS-2 Social Affect (SA) scores (14.051 vs. 11.125; p < 0.01) as well as Restrictive and Repetitive Behavior (RRB) scores (5.258 vs. 3.875; p < 0.005) were both significantly increased in the non-syndromic ASD group relative to the Fragile X Syndrome (FXS)-ASD group, indicating more severe autistic behaviors in the non-syndromic ASD group (Table 1)
One of the main goals of this study was to further contribute to the body of knowledge regarding phenotypic similarities and the differences between non-syndromic ASD and fragile Xassociated ASD, and our results support the findings of recent studies showing qualitatively different autism profiles between these two populations

Summary

Introduction

Autism spectrum disorder (ASD) is a behaviorally defined neurodevelopmental disorder that is characterized by impaired social and language development, repetitive behaviors, and restricted interests, as well as hyper or hypo-reactivity to sensory inputs. Despite the often-multifactorial nature of the disorder, ASD can be caused by single gene mutations. The most common singlegene cause of ASD is Fragile X Syndrome (FXS). The clinical presentation of FXS and idiopathic ASD overlap significantly, with a number of neurologic and behavioral characteristics seen in both conditions. These include language deficits, poor eye contact, repetitive behaviors, perseverative speech, hypersensitivity to environmental stimuli, ADHD, anxiety, and social deficits [4,5,6]

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