Explorations of the E/I imbalance framework of autism

Neural mechanisms and genetic factors

Viola Hollestein • Boek • paperback

• Samenvatting
  Free download at https://doi.org/10.54195/9789465150819
  Autism (Autism Spectrum Disorder) is one of the most common neurodevelopmental conditions. Yet, there is much that remains unknown about its underlying mechanisms in the brain, how it develops, and the various expressions of autism across individuals. This thesis presents a series of studies on the excitation/inhibition (E/I) imbalance theory of autism, aiming to disentangle some of the heterogeneities by linking genetic underpinnings of glutamatergic (excitation) and GABAergic (inhibition) functions, neuroimaging measures and behavioral autism characteristics.
  The findings in this thesis illustrate a central role of glutamate and GABA in driving the physiology and behaviors associated with autism. ACC glutamate concentration changes in autism are associated with repetitive behaviors (Chapter 2) and similarly, affect variation in brain structure (Chapter 3). Moreover, polygenic scores for glutamate appear to drive these differences in ACC glutamate concentrations (Chapter 5), which links genetic information to metabolite levels in autism for the first time. This interaction subsequently affects a wide range of behaviors including social difficulties and sensory difficulties. I also found interactions between glutamate and GABA as complex interplays between genetic and MRS markers of excitation and inhibition whereby glutamate and GABA differentially appear to affect behavioral autism characteristics (Chapter 5). These findings are not enough to clearly distinguish which alteration in E/I mechanisms lead to what behavioral characteristic of autism, but functions as a valuable first step to further investigate these associations in more detail. It also shows the importance of including both glutamate and GABA measures in investigations of E/I mechanisms, while also taking age of participants into account, as these seem to interact and have strong effects on findings, which in turn will help explain heterogeneities and developmental differences across autistic individuals. Ultimately, the findings of this thesis argues for the urgent need for continuing to use dimensional and multimodal approaches to really disentangle the biological etiologies of the heterogeneities of autism.
• Productinformatie
  Binding : Paperback
  Distributievorm : Boek (print, druk)
  Formaat : 170mm x 240mm
  Aantal pagina's : 267
  Uitgeverij : Radboud University Press
  ISBN : 9789465150819
  Datum publicatie : 06-2025
  
• Inhoudsopgave
  niet beschikbaar
• Reviews (0 uit 0 reviews)
  Wil je meer weten over hoe reviews worden verzameld? Lees onze uitleg hier.