Networking in Autism: Leveraging Genetic, Biomarker and Model System Findings in the Search for New Treatments

Veenstra-VanderWeele, Jeremy; Blakely, Randy D

doi:10.1038/npp.2011.185

Cited by 128Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersChild Nutrition and Feeding Issues

Networking in Autism: Leveraging Genetic, Biomarker and Model System Findings in the Search for New Treatments

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Veenstra-VanderWeele, Jeremy, Blakely, Randy D·2012·Neuropsychopharmacology

DOI 10.1038/npp.2011.185PMC PMC3238072

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Abstract

Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder affecting approximately 1% of children. ASD is defined by core symptoms in two domains: negative symptoms of impairment in social and communication function, and positive symptoms of restricted and repetitive behaviors. Available treatments are inadequate for treating both core symptoms and associated conditions. Twin studies indicate that ASD susceptibility has a large heritable component. Genetic studies have identified promising leads, with converging insights emerging from single-gene disorders that bear ASD features, with particular interest in mammalian target of rapamycin (mTOR)-linked synaptic plasticity mechanisms. Mouse models of these disorders are revealing not only opportunities to model behavioral perturbations across species, but also evidence of postnatal rescue of brain and behavioral phenotypes. An intense search for ASD biomarkers has consistently pointed to elevated platelet serotonin (5-HT) levels and a surge in brain growth in the first 2 years of life. Following a review of the diversity of ASD phenotypes and its genetic origins and biomarkers, we discuss opportunities for translation of these findings into novel ASD treatments, focusing on mTor- and 5-HT-signaling pathways, and their possible intersection. Paralleling the progress made in understanding the root causes of rare genetic syndromes that affect cognitive development, we anticipate progress in models systems using bona fide ASD-associated molecular changes that have the potential to accelerate the development of ASD diagnostics and therapeutics.

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Biological abnormalities have been reported in eye tracking, neuroanatomical pathway connectivity, brain regional volumes, cortical activation during social and communication tasks, serotonin levels, and other biological assays, but not with sufficient consistency to constitute uniform diagnostic biomarkers.
“Biological abnormalities have been reported in eye tracking, neuroanatomical pathway connectivity, brain regional volumes, cortical activation during social and communication tasks as measured with functional magnetic resonance imaging and magnetoencephalography, serotonin levels, and other biological assays, but not with sufficient consistency for these to constitute uniform diagnostic biomarkers”
From Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism (2012) · cites this paper as [94]

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“Again, as diagnosis rates have increased in the general population, recurrence rates within families have increased as well, with estimates ranging from 3 to 11% in large samples (Bolton et al, 1994; Constantino et al, 2010b; Jorde et al, 1991; Ritvo et al, 1989).”
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Retracted
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Authors: Veenstra-VanderWeele, J., & Blakely, R. D.
Affiliations: Vanderbilt University (US)
Corresponding author: Blakely, Randy D
ORCID: Veenstra-VanderWeele, Jeremy
Blakely, Randy D
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2011-09-21
Volume: 37
Issue: 1
Pages: 196-212
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/npp.2011.185
PMC: PMC3238072
OpenAlex: W2099789197
Cited by: 128
References: 258
Citations by year: 2026: 1 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 13 · 2020: 6 · 2019: 8 · 2018: 4 · 2017: 9 · 2016: 7 · 2015: 13 · 2014: 21 · 2013: 13 · 2012: 11
FWCI: 1.28
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Neuropsychopharmacology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (MH078028)
National Institute of Mental Health (R01MH094527, K08MH081066, MH081066, P50MH078028, MH078028, MH094604, MH094527, R01MH094604)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD065278, R01HD065278)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
Keywords: autism spectrum disorder, mTOR signaling, synaptic plasticity, platelet serotonin, biomarkers, mouse models of autism, monogenic disorders, translational research, brain growth, heritability, rare genetic disorders
MeSH terms: Animals, Autistic Disorder, Disease Models, Animal, Humans, Psychotropic Drugs, Signal Transduction, Biomarkers, Genetic Predisposition to Disease, Mice

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Networking in Autism: Leveraging Genetic, Biomarker and Model System Findings in the Search for New Treatments

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