Modeling dopamine dysfunction in autism spectrum disorder: From invertebrates to vertebrates

Autism Spectrum Disorder (ASD) is a highly heterogeneous neurodevelopmental disorder characterized by deficits in social communication and by patterns of restricted interests and/or repetitive behaviors. The Simons Foundation Autism Research Initiative's Human Gene and CNV Modules now list over 1000 genes implicated in ASD and over 2000 copy number variant loci reported in individuals with ASD. Given this ever-growing list of genetic changes associated with ASD, it has become evident that there is likely not a single genetic cause of this disorder nor a single neurobiological basis of this disorder. Instead, it is likely that many different neurobiological perturbations (which may represent subtypes of ASD) can result in the set of behavioral symptoms that we called ASD. One such of possible subtype of ASD may be associated with dopamine dysfunction. Precise regulation of synaptic dopamine (DA) is required for reward processing and behavioral learning, behaviors which are disrupted in ASD. Here we review evidence for DA dysfunction in ASD and in animal models of ASD. Further, we propose that these studies provide a scaffold for scientists and clinicians to consider subcategorizing the ASD diagnosis based on the genetic changes, neurobiological difference, and behavioral features identified in individuals with ASD.

Automated summary

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and restricted interests/repetitive behaviors. Over 1000 genes and 2000 copy number variants have been implicated in ASD. It is believed that there is not a single genetic cause or neurobiological basis for ASD, but rather multiple subtypes with different genetic and neurobiological perturbations. Dopamine dysfunction may be one potential subtype associated with ASD. This research provides a framework for subcategorizing ASD based on genetic changes, neurobiological differences, and behavioral features.