Additive effects of oxytocin receptor gene polymorphisms on reward circuitry in youth with autism
Open accessAbstract
Several common alleles in the oxytocin receptor gene (OXTR) are associated with altered brain function in reward circuitry in neurotypical adults and may increase risk for autism spectrum disorders (ASD). Yet, it is currently unknown how variation in the OXTR relates to brain functioning in individuals with ASD, and, critically, whether neural endophenotypes vary as a function of aggregate genetic risk. Here, for we believe the first time, we use a multi-locus approach to examine how genetic variation across several OXTR single-nucleotide polymorphisms (SNPs) affect functional connectivity of the brain's reward network. Using data from 41 children with ASD and 41 neurotypical children, we examined functional connectivity of the nucleus accumbens (NAcc) - a hub of the reward network - focusing on how connectivity varies with OXTR risk-allele dosage. Youth with ASD showed reduced NAcc connectivity with other areas in the reward circuit as a function of increased OXTR risk-allele dosage, as well as a positive association between risk-allele dosage and symptom severity, whereas neurotypical youth showed increased NAcc connectivity with frontal brain regions involved in mentalizing. In addition, we found that increased NAcc-frontal cortex connectivity in typically developing youth was related to better scores on a standardized measure of social functioning. Our results indicate that cumulative genetic variation on the OXTR impacts reward system connectivity in both youth with ASD and neurotypical controls. By showing differential genetic effects on neuroendophenotypes, these pathways elucidate mechanisms of vulnerability versus resilience in carriers of disease-associated risk alleles.
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Polymorphisms in OXTR contribute to sexually dimorphic alterations in functional connectivity between the NAc and PFC.
“Polymorphisms in OXTR also contribute to sexually dimorphic alterations in functional connectivity between the NAc and PFC [35,36].”
From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [36]
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Oxytocin and autism – A precision medicine framework to unpack mechanisms and evidence
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Association Between HLA-B Polymorphisms and Autism Spectrum Disorder in Chinese Population
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- Authors
- Hernandez, L. M., Krasileva, K., Green, S. A., Sherman, L. E., Ponting, C., McCarron, R., Lowe, J. K., Geschwind, D. H., Bookheimer, S. Y., & Dapretto, M.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Dapretto, M
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2016-11-15
- Volume
- 22
- Issue
- 8
- Pages
- 1134-1139
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC5991611
- OpenAlex
- W2554596146
- Cited by
- 43
- References
- 60
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 6 · 2020: 7 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 1
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Ahmanson Foundation
- Brain Mapping Support Foundation
- Pierson-Lovelace Foundation
- Institut National de la Santé et de la Recherche Médicale
- National Institutes of Health (1s10od011939-01a1)
- National Institute of Mental Health (K08MH112871, F32MH105167, T32MH073526, HD055784, R01MH100028)
- National Institute on Drug Abuse (F31DA038578)
- National Institute of Child Health and Human Development
- National Center for Research Resources (S10OD011939, C06RR015431, C06RR012169)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD087101, P50HD055784)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- oxytocin receptor gene, OXTR polymorphisms, autism spectrum disorder, reward systems, nucleus accumbens, functional connectivity, cumulative genetic risk, endophenotypes, symptom severity, social functioning, mentalization, children
- MeSH terms
- Autism Spectrum Disorder, Adolescent, Alleles, Autistic Disorder, Brain, Child, Female, Frontal Lobe, Gene Frequency, Humans, Male, Nucleus Accumbens, Oxytocin, Reward, Social Behavior, Genetic Variation, Case-Control Studies, Receptors, Oxytocin, Gene Dosage, Polymorphism, Single Nucleotide, Neuroimaging
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