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Cited by 39Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersNeurotransmitter Receptor Influence on Behavior

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

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DiCarlo, Gabriella E., Wallace, Mark T.·2022·Neuroscience & Biobehavioral Reviews
DOI 10.1016/j.neubiorev.2021.12.017PMC PMC8792250
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Abstract

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.

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  • Few studies have assessed variations in the levels of DA, its metabolites or the activity of enzymes involved in DA metabolism in the blood, as DA cannot cross the blood-brain barrier.

    “It is mentioned that few studies have assessed variations in the levels of DA, its metabolites or the activity of enzymes involved in DA metabolism in the blood, as DA cannot cross the blood-brain barrier.”

    From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as DiCarlo and Wallace, 2022

    In “Evidence for DA dysfunction in ASD” (page unavailable), the paper says many studies measured dopamine-related indices in plasma, platelets, urine, and cerebrospinal fluid—not that few studies assessed them. It confirms that dopamine cannot cross the blood-brain barrier, but gives that as a reason peripheral measurements may poorly reflect brain activity, not as a reason few studies were conducted. (LLM, conf=0.88)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • Brain imaging studies are generally more accurate in showing dysfunction of the central DA system in ASD.

    “Rather, brain imaging studies are generally more accurate in showing dysfunction of the central DA sys­ tem in ASD (DiCarlo and Wallace, 2022).”

    From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as DiCarlo and Wallace, 2022

    In “Evidence for DA dysfunction in ASD” (page not supplied), the review says brain imaging findings are more consistent than peripheral measures and describes evidence of differences in DA-related structures and connectivity. It does not establish that imaging is generally more accurate at showing central DA dysfunction; it cautions that those differences could arise from other mechanisms. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
DiCarlo, G. E., & Wallace, M. T.
Affiliations
  • Massachusetts General Hospital (US)
  • Vanderbilt University (US)
Corresponding author
Wallace, Mark T.
ORCID
Venue
Neuroscience & Biobehavioral Reviews
Publisher
Elsevier BV
Published
2022-02
Volume
133
Pages
104494
ISSN
0149-7634 (ISSN-L)
DOI
10.1016/j.neubiorev.2021.12.017
PMC
PMC8792250
OpenAlex
W4200193312
Cited by
39
References
51
Citations by year
2026: 12 · 2025: 9 · 2024: 9 · 2023: 4 · 2022: 5
FWCI
0.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuroscience & Biobehavioral Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (F30MH115535, P50HD103537, T32GM007347)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
autism spectrum disorder, dopaminergic dysfunction, synaptic dopamine, reward processing, behavioral learning, animal models of autism, copy number variation, genetic heterogeneity, ASD subtypes, social communication deficits, invertebrate models
MeSH terms
Autism Spectrum Disorder, Animals, Autistic Disorder, Dopamine, Humans, Invertebrates, Vertebrates

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