The neurobiological presentation of anxiety in autism spectrum disorder: A systematic review

Abstract

Anxiety is common among people with autism and is associated with unique and additive challenges. Anxiety is thought to have neurobiological components, and measures of arousal in typical development have long been studied. Recently, neurobiological measures of anxiety in autism have begun to receive empirical evaluation, but results have not yet been examined together. This systematic review, therefore, summarizes the state of the research of the neurobiology of anxiety in autism. Studies published between 1999 and June 2017 were reviewed. Results across measures of arousal point to inconsistencies in results and a lack of synthesis in the literature. Considerations regarding these inconsistencies are discussed, recommendations for future studies are offered, and clinical implications for this work are presented. Autism Res 2019, 12: 346–369 © 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Anxiety is common among people with autism. Because anxiety has been linked with a variety of differences in physiological (bodily) and neurophysiological (brain) functioning in people without autism, research has begun to examine these processes in autism as well. This literature, however, has not yet been examined as a whole. Therefore, this paper begins to address that gap to provide the field with a better understanding of how anxiety affects people with autism and discusses implications for future research and clinical practice.

Region-Specific Reduction of BDNF Protein and Transcripts in the Hippocampus of Juvenile Rats Prenatally Treated With Sodium Valproate

“…In the present study, we assessed the long-term effect of embryonic exposure to VPA on the performance in specific behavioral tasks at a juvenile stage. At PN30, we observed anxiety-like behavior in the elevated plus maze; change that has been described in this model (Markram et al, 2008) and in ASD patients (McVey, 2019). In relation to social interaction, VPA-animals did not discriminate between social and non-social areas, suggesting an alteration in the motivational component of social behavior, rather than social aversion, finding which is in line with the “Social Motivation Theory of Autism” (Chevallier et al, 2012).…”

Heterozygous loss of epilepsy geneKCNQ2alters social, repetitive and exploratory behaviors

“…The increased exploratory behavior of KCNQ2 +/− mice in these tests suggests that heterozygous loss of K v 7.2 reduces anxiety‐related behavior in mice. This is somewhat contrary to the well‐documented reports that patients with ASD experience greater anxiety than those without ASD . However, multiple mouse models of autism and Fragile X Syndrome (FXS) which accounts for about 2% to 3% of all ASD cases show reduced nonsocial anxiety measured by the same behavioral tests although they display typical autism‐associated behaviors including social avoidance and repetitive behaviors .…”

“…This is somewhat contrary to the well-documented reports that patients with ASD experience greater anxiety than those without ASD. 7 However, multiple mouse models of autism and Fragile X Syndrome (FXS) which accounts for about 2% to 3% of all ASD cases show reduced nonsocial anxiety measured by the same behavioral tests although they display typical autism-associated behaviors including social avoidance and repetitive behaviors. [82][83][84][85][86] For example, FXS mouse model Fmr1 F I G U R E 8 The KCNQ2 +/− mice display increased seizure propensity to chemoconvulsant kainate and enhanced hippocampal excitability.…”

“…3 Additional ASD symptoms include obsessive interests, compulsive behavior, impulsivity, self-harm, aggression, hyperactivity, anxiety, hypersensitivity to auditory and tactile stimulation, sleep problems, learning disability and speech delay. [4][5][6][7][8][9] Current available treatments for children with NDDs have limited efficacy alleviating the behavioral symptoms associated with ASD and seizures that are comorbid with some NDDs. 10 To understand the etiology underlying NDDs, recent efforts have focused on next generation sequencing of whole genome and targeted sequencing of well-defined ASD cohorts.…”

“…The main symptoms of ASD are behavioral abnormalities including difficulty with social interaction and communication as well as restrictive and repetitive behaviors . Additional ASD symptoms include obsessive interests, compulsive behavior, impulsivity, self‐harm, aggression, hyperactivity, anxiety, hypersensitivity to auditory and tactile stimulation, sleep problems, learning disability and speech delay . Current available treatments for children with NDDs have limited efficacy alleviating the behavioral symptoms associated with ASD and seizures that are comorbid with some NDDs .…”