Plasma oxytocin concentrations and OXTR polymorphisms predict social impairments in children with and without autism spectrum disorder
Open accessAbstract
Significance: The neuropeptide oxytocin (OXT) is critically involved in mammalian social functioning, and initial clinical research suggests that OXT biology may be altered in individuals with autism spectrum disorder (ASD). Here we provide important evidence that blood OXT concentrations are highly heritable within families, yet also strongly predict social functioning in ASD children, their unaffected siblings, and healthy control children. These findings also extend to OXT receptor genotypes which are significantly associated with differences in social functioning independent of disease status. These findings indicate that dysregulated OXT biology is not uniquely associated with ASD social phenotypes as widely theorized, but instead variation in OXT biology contributes to important individual differences in human social functioning, including the severe social impairments which characterize ASD.
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Polymorphisms in the human OXTR gene are significantly associated with an ASD diagnosis and/or predict the severity of ASD.
“many of these genetic studies have found that polymorphisms in the human OXT receptor (OXTR) gene are significantly associated with an ASD diagnosis and/or predict the severity of ASD4–12.”
From Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain (2018) · cites this paper as [5]
Human studies have linked intronic OXTR variants to individual differences in functional connectivity among brain regions while processing social information.
“Recent research in humans found that intronic OXTR variants predicted individual differences in functional connectivity between brain regions during the processing of social information (80, 81).”
From Variation in the Oxytocin Receptor Gene Predicts Brain Region–Specific Expression and Social Attachment (2016) · cites this paper as [81]
Despite challenges, there is an increasing body of evidence showing that oxytocin can be used as a biomarker of social functioning.
“However, despite these above challenges, there is an increasing body of evidence showing that OT can be used as a biomarker of social functioning (Andari et al. 2014; Parker et al. 2014).”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Parker et al. 2014
Plasma oxytocin concentration and OTR polymorphisms correlate with social aptitudes in children with and without autism.
“Recently, Parker et al. (2014) reported that plasma oxytocin concentration and OTR polymorphisms correlate with social aptitudes in children with and without autism (Parker et al. 2014).”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Parker et al. 2014
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“Nevertheless, the OXT system is a leading candidate target for improving social function in patients with psychiatric disorders such as autism spectrum disorder (ASD) and schizophrenia (12–17), and one report suggested that OXTR expression may be reduced in ASD (18).”
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“All of the SNPs associated with ASD or social behaviors lie within non-coding regions of OXTR, suggesting that the impact on behavior is mediated by variation in OXTR expression, not structure.”
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“Parker et al. (2014) revealed that plasma concentrations of OT strongly predicted ToM in children with ASD, their unaffected siblings, and unrelated typically developing controls.”
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“The aberrant OXT serum levels have been reported in ASD individuals to varying degrees, sometimes decreased [58,59], sometimes no difference [60,61], and sometimes enriched compared to non-ASD controls [62].”
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“Polymorphisms in the oxytocin receptor gene have been associated with deficits in social behaviors in humans (Lerer et al., 2010; Parker et al., 2014; LoParo and Waldman, 2015).”
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“, 2018)) and promotes social behavior, in both animals and humans (Lukas and Neumann, 2013; Parker et al., 2014).”
BackgroundOxytocin levels tend to be lower in autistic children: A meta-analysis of 31 studies
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“Together with studies relating OT levels to socio-cognitive functions in neurotypical individuals as well as in siblings of autistic children (Parker et al., 2014), our finding is consistent with OT levels mediating a continuous range of socio-cognitive function, at the extreme of which are autistic people (Crespi, 20…”
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“Besides autism, rs2254298 was also linked to social impairment in general (Parker et al., 2014), empathy (Wu et al.”
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Nomi, J. S., Molnar-Szakacs, I., & Uddin, L. Q. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.10.015 · Cited by 95 · see citing works
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Alvares, G. A., Quintana, D. S., & Whitehouse, A. J. O. (2017) · Autism Research · doi:10.1002/aur.1692 · Cited by 91 · see citing works
“…control group in these studies also differs, with some studies comparing matched blood samples from typically developing samples [Al-Ayadhi, 2005; Jansen et al., 2006; Miller et al., 2013; Modahl et al., 1998; Parker et al., 2014] and others using existing normative data [Andari et al., 2010].”
BackgroundResultInfluentialAdaptations for social cognition in the primate brain
Platt, M. L., Seyfarth, R. M., & Cheney, D. L. (2016) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2015.0096 · Cited by 87 · see citing works
Autism Biomarkers: Challenges, Pitfalls and Possibilities
Anderson, G. M. (2014) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-014-2225-4 · Cited by 82 · see citing works
“More recently it has been reported that mean plasma oxytocin levels do not differ between autism and comparison groups; rather, levels were observed to be positively associated with social functioning across groups (Parker et al. 2014).”
BackgroundDrug development for Autism Spectrum Disorder (ASD): Progress, challenges, and future directions
McCracken, J. T., Anagnostou, E. A., Arango, C., Dawson, G., Farchione, T. R., Mantua, V., McPartland, J. C., Murphy, D., Pandina, G., & Veenstra-VanderWeele, J. M. (2021) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2021.05.010 · Cited by 87 · see citing works
Li, Q., Becker, B., Wernicke, J., Chen, Y., Zhang, Y., Li, R., Le, J., Kou, J., Zhao, W., & Kendrick, K. M. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.11.016 · Cited by 85 · see citing works
Arginine Vasopressin Is a Blood-Based Biomarker of Social Functioning in Children with Autism
Carson, D. S., Garner, J. P., Hyde, S. A., Libove, R. A., Berquist, S. W., Hornbeak, K. B., Jackson, L. P., Sumiyoshi, R. D., Howerton, C. L., Hannah, S. L., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0132224 · Cited by 71 · see citing works
Self-citationDevelopmental changes in social attention and oxytocin levels in infants and children
Nishizato, M., Fujisawa, T. X., Kosaka, H., & Tomoda, A. (2017) · Scientific Reports · doi:10.1038/s41598-017-02368-x · Cited by 72 · see citing works
Arginine vasopressin in cerebrospinal fluid is a marker of sociality in nonhuman primates
Parker, K. J., Garner, J. P., Oztan, O., Tarara, E. R., Li, J., Sclafani, V., Del Rosso, L. A., Chun, K., Berquist, S. W., Chez, M. G., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aam9100 · Cited by 64 · see citing works
Attachment style and oxytocin receptor gene variation interact in influencing social anxiety
Notzon, S., Domschke, K., Holitschke, K., Ziegler, C., Arolt, V., Pauli, P., Reif, A., Deckert, J., & Zwanzger, P. (2016) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2015.1091502 · Cited by 65 · see citing works
“Moons et al. (2014) observed significantly lower oxytocin plasma levels in carriers of two G alleles, while Parker et al. (2014) found no differences in oxytocin plasma levels depending on OXTR rs53576 comparing G allele carriers with AA homozygotes.”
Kou, J., Zhang, Y., Zhou, F., Sindermann, C., Montag, C., Becker, B., & Kendrick, K. M. (2020) · Psychological Medicine · doi:10.1017/s0033291720003803 · Cited by 63 · see citing works
ASD and Genetic Associations with Receptors for Oxytocin and Vasopressin—AVPR1A, AVPR1B, and OXTR
Francis, S. M., Kim, S., Kistner‐Griffin, E., Guter, S. J., Cook, E. H., & Jacob, S. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00516 · Cited by 62 · see citing works
“This SNP has been affiliated with social impairment in two recent studies, Parker et al. (2014) found rs2254298 to be associated with social impairment in an ASD and typically developing sample.”
ResultWeisman, O., Pelphrey, K. A., Leckman, J. F., Feldman, R., Lu, Y., Chong, A., Chen, Y., Monakhov, M. V., Chew, S. H., & Ebstein, R. P. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.04.007 · Cited by 60 · see citing works
“Studies that report of associations between the functioning of the oxytocinergic system and socio-emotional competencies in humans continue to emerge—–both in typically-developing individuals as well as in samples characterized by sub-optimal social functioning (Parker et al., 2014; Skuse et al., 2014; Weisman et al.,…”
Magiati, I., Lerh, J. W., Hollocks, M. J., Uljarević, M., Rodgers, J., McConachie, H., Ozsivadjian, A., South, M., Hecke, A. V. V., Hardan, A. Y., et al. (2017) · Autism Research · doi:10.1002/aur.1809 · Cited by 58 · see citing works
Self-citationSippel, L. M., Han, S., Watkins, L. E., Harpaz‐Rotem, I., Southwick, S. M., Krystal, J. H., Olff, M., Sherva, R., Farrer, L. A., Kranzler, H. R., et al. (2017) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2017.07.008 · Cited by 57 · see citing works
“…related rs53576 or other OXTR variants to human plasma oxytocin levels, and results have thus far been inconsistent, showing both lower levels of oxytocin plasma in rs53576 G homozygotes (Moons et al., 2014) and no difference between individuals with G/A and A/A genotypes (Parker et al., 2014).”
BackgroundResultEndocannabinoid signaling in social functioning: an RDoC perspective
Karhson, D. S., Hardan, A. Y., & Parker, K. J. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.169 · Cited by 62 · see citing works
Self-citationAttempted suicide and oxytocin-related gene polymorphisms
Parris, M. S., Grunebaum, M. F., Galfalvy, H., Andronikashvili, A., Burke, A. K., Yin, H., Min, E., Huang, Y., & Mann, J. J. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.05.022 · Cited by 56 · see citing works
Oxytocin in animal models of autism spectrum disorder
Peñagarikano, O. (2016) · Developmental Neurobiology · doi:10.1002/dneu.22449 · Cited by 54 · see citing works
“As mentioned above, this association likely reflects natural variation in the social cognition behavioral domain as the same genetic variants or oxytocin plasma levels are associated with variation in social cognition in the general population (Parker et al., 2014; Skuse et al., 2014).”
BackgroundBakker-Huvenaars, M. J., Greven, C. U., Herpers, P., Wiegers, E., Jansen, A., van der Steen, R., van Herwaarden, A. E., Baanders, A. N., Nijhof, K. S., Scheepers, F., et al. (2020) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2018.07.097 · Cited by 51 · see citing works
Kohlhoff, J. R., Cibralic, S., Hawes, D. J., & Eapen, V. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104573 · Cited by 50 · see citing works
Plasma oxytocin explains individual differences in neural substrates of social perception
Lancaster, K., Carter, C. S., Pournajafi‐Nazarloo, H., Karaoli, T., Lillard, T. S., Jack, A., Davis, J. M., Morris, J. P., & Connelly, J. J. (2015) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2015.00132 · Cited by 52 · see citing works
The oxytocin receptor gene predicts brain activity during an emotion recognition task in autism
Uzefovsky, F., Bethlehem, R. A. I., Shamay-Tsoory, S., Ruigrok, A., Holt, R., Spencer, M., Chura, L., Warrier, V., Chakrabarti, B., Bullmore, E., et al. (2019) · Molecular Autism · doi:10.1186/s13229-019-0258-4 · Cited by 49 · see citing works
“Single nucleotide polymorphisms (SNPs) in the OXTR have been associated with autism in different populations [24–30], especially related to the social domain in autism [31, 32], although null-findings are also reported [33–35].”
ResultNovel treatments for autism spectrum disorder based on genomics and systems biology
Baribeau, D. A., & Anagnostou, E. A. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107939 · Cited by 50 · see citing works
Torres, N., Martins, D., dos Santos, A. J., Prata, D. P., & Veríssimo, M. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.05.004 · Cited by 46 · see citing works
Urinary and plasma oxytocin changes in response to MDMA or intranasal oxytocin administration
Francis, S. M., Kirkpatrick, M. G., de Wit, H., & Jacob, S. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.08.011 · Cited by 46 · see citing works
Itskovich, E., Zyga, O., Libove, R. A., Phillips, J. M., Garner, J. P., & Parker, K. J. (2020) · Autism Research · doi:10.1002/aur.2409 · Cited by 51 · see citing works
“, 1997], neither social motivation nor social skill differed between unaffected siblings and NT controls in the present study, nor have these two groups differed in other behavioral or biological variables of interest [Carson et al., 2015; Parker et al., 2014].”
BackgroundMethodResultSelf-citationBetween Dysbiosis, Maternal Immune Activation and Autism: Is There a Common Pathway?
Suprunowicz, M., Tomaszek, N., Urbaniak, A., Zackiewicz, K., Modzelewski, S., & Waszkiewicz, N. (2024) · Nutrients · doi:10.3390/nu16040549 · Cited by 44 · see citing works
“Moreover, polymorphisms in the oxytocin receptor genes are related to symptom severity of ASD [282].”
BackgroundBaribeau, D. A., Dupuis, A., Paton, T., Scherer, S. W., Schachar, R. J., Arnold, P. D., Szatmári, P., Nicolson, R., Georgiades, S., Crosbie, J., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-10821-0 · Cited by 45 · see citing works
McDonald, N. M., Baker, J. K., & Messinger, D. S. (2016) · Developmental Psychology · doi:10.1037/dev0000104 · Cited by 43 · see citing works
“, 2012) have lower levels of plasma or salivary oxytocin, while others have found no difference in plasma or salivary oxytocin for either SNP (Bhandari et al., 2014; Parker et al., 2014).”
BackgroundStohn, J. P., Martinez, M. E., Zafer, M., López-Espíndola, D., Keyes, L. M., & Hernández, A. (2017) · Genes Brain & Behavior · doi:10.1111/gbb.12400 · Cited by 41 · see citing works
“ing ASD, schizophrenia and depression (Domes et al. 2016; Miller et al. 2013; Modahl et al. 1998; Neumann & Landgraf 2012; Parker et al. 2014; Sasayama et al. 2012; Strauss et al. 2015a; Thompson et al. 2014; Uhrig et al. 2016; Wu et al. 2005; Zhang et al. 2016).”
BackgroundA precision medicine approach to oxytocin trials
Andari, E., Hurlemann, R., & Young, L. J. (2017) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2017_29 · Cited by 40 · see citing works
Yang, S., Dong, X., Guo, X., Han, Y., Song, H., Gao, L., Dai, W., Su, Y., & Zhang, X. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00221 · Cited by 40 · see citing works
“Because plasma OT concentrations are highly heritable (Parker et al., 2014), family effects should be taken into consideration in subsequent studies.”
BackgroundResultClinical and Neurobiological Relevance of Current Animal Models of Autism Spectrum Disorders
Kim, K. C., Gonzales, E. L., Lázaro, M. T., Choi, C. S., Bahn, G. H., Yoo, H. J., & Shin, C. Y. (2016) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2016.061 · Cited by 40 · see citing works
“Additional studies further support these later findings by finding a positive correlation between Oxtr polymorphisms and social recognition skills, thus suggesting Oxtr SNPs as predictors of social impairments in both typically developing individuals and in children with ASD (Parker et al., 2014).”
ResultTops, S., Habel, U., & Radke, S. (2018) · Hormones and Behavior · doi:10.1016/j.yhbeh.2018.03.002 · Cited by 39 · see citing works
“Complementing the main impairments of ASD given in the introduction, other behaviors characteristic for ASD include deficits in eye contact, facial recognition, and lack of social and emotional reciprocity (Jacob et al., 2007; Parker et al., 2014).”
BackgroundOlfactory stem cells reveal MOCOS as a new player in autism spectrum disorders
Feron, F. P., Gepner, B., Lacassagne, E., Stephan, D., Mesnage, B., Blanchard, M.-P., Boulanger, N., Tardif, C., Devèze, A., Rousseau, S., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.106 · Cited by 38 · see citing works
“Notably, 9 out of these 156 genes – ADAM23 , CADM1 , FOS , FOSB , JAG1 , MEST , OXTR , SFRP1 and XIST – have been previously associated to ASD(Parker et al., 2014).”
The importance of early life touch for psychosocial and moral development
Narvaez, D. F., Wang, L., Cheng, A. S., Gleason, T. R., Woodbury, R. D., Kurth, A. M., & Lefever, J. B. (2019) · Psicologia Reflexão e Crítica · doi:10.1186/s41155-019-0129-0 · Cited by 44 · see citing works
Simpson, E. A., Paukner, A., Sclafani, V., Kaburu, S., Suomi, S. J., & Ferrari, P. F. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4480-x · Cited by 36 · see citing works
“Further, in human children, plasma OT levels are a highly heritable trait, positively associated with social functioning (Parker et al. 2014) and negatively associated with trait anxiety (Carson et al. 2015).”
BackgroundBiomarker discovery for disease status and symptom severity in children with autism
Oztan, O., Jackson, L. P., Libove, R. A., Sumiyoshi, R. D., Phillips, J. M., Garner, J. P., Hardan, A. Y., & Parker, K. J. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.12.022 · Cited by 37 · see citing works
“A technician blinded to experimental conditions performed sample preparation and OXT and AVP quantification following established procedures (Carson et al., 2015; Parker et al., 2014).”
BackgroundMethodResultInfluentialSelf-citationInterplay between the oxytocin and opioid systems in regulating social behaviour
Putnam, P. T., & Chang, S. W. C. (2022) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2021.0050 · Cited by 33 · see citing works
The Potential of Nasal Oxytocin Administration for Remediation of Autism Spectrum Disorders
Okamoto, Y., Ishitobi, M., Wada, Y., & Kosaka, H. (2016) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527315666160413120845 · Cited by 33 · see citing works
Oxytocin: A citation network analysis of 10 000 papers
Leng, G., & Leng, R. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.13014 · Cited by 33 · see citing works
Structure-function relationships of the disease-linked A218T oxytocin receptor variant
Meyer, M., Jurek, B., Alfonso‐Prieto, M., Ribeiro, R. P., Milenkovic, V. M., Winter, J. J., Hoffmann, P., Wetzel, C. H., Giorgetti, A., Carloni, P., et al. (2022) · Molecular Psychiatry · doi:10.1038/s41380-021-01241-8 · Cited by 33 · see citing works
“For example, synthetic OXT, which can be applied intranasally and penetrates brain tissue [21, 22] has been shown to improve social deficits in autistic children [23, 24].”
BackgroundJurek, B., & Meyer, M. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00186 · Cited by 32 · see citing works
“, hyperconnectivity, and symptoms of autism spectrum disorder (67); moreover, lower plasma oxytocin levels have been reported in children with autism and social impairments (68, 69).”
BackgroundCattaneo, Z., Daini, R., Malaspina, M., Manai, F., Lillo, M., Fermi, V., Schiavi, S., Boris Suchan, A., & Comincini, S. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.09.040 · Cited by 31 · see citing works
Fang, Y., Cui, Y., Yin, Z., Hou, M., Guo, P., Wang, H., Liu, N., Cai, C., & Wang, M. (2023) · Gene · doi:10.1016/j.gene.2023.147723 · Cited by 37 · see citing works
Morphofunctional Alterations of the Hypothalamus and Social Behavior in Autism Spectrum Disorders
Carìa, A., Ciringione, L., & de Falco, S. (2020) · Brain Sciences · doi:10.3390/brainsci10070435 · Cited by 29 · see citing works
“Several investigations also reported an association of the levels of peripheral OT and oxytocin receptor (OXTR) polymorphisms with the diagnosis and severity of ASD [29].”
BackgroundMunesue, S., Liang, M., Harashima, A., Zhong, J., Furuhara, K., Boitsova, E. B., Михайлович, Ч. С., Gerasimenko, M., Yuhi, T., Yamamoto, Y., et al. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.12963 · Cited by 32 · see citing works
Perception of social interaction compresses subjective duration in an oxytocin-dependent manner
Liu, R., Yuan, X., Chen, K., Jiang, Y., & Zhou, W. (2018) · eLife · doi:10.7554/elife.32100 · Cited by 29 · see citing works
“This inter-individual variance has been associated with plasma concentrations of oxytocin, a well-documented prosocial neuropeptide, as well as polymorphisms of its receptor gene OXTR (Andari et al., 2014; Donaldson and Young, 2008; Modahl et al., 1998; Parker et al., 2014; Skuse et al., 2014; Tost et al., 2010).”
BackgroundInfluentialAcute and Repeated Intranasal Oxytocin Differentially Modulate Brain-wide Functional Connectivity
Pagani, M., Felice, A. D., Montani, C., Galbusera, A., Papaleo, F., & Gozzi, A. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2019.12.036 · Cited by 27 · see citing works
Francis, S. M., Kistner‐Griffin, E., Yan, Z., Guter, S. J., Cook, E. H., & Jacob, S. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00195 · Cited by 26 · see citing works
“Parker et al. (2014) found the OT receptor gene (OXTR) SNP rs2254298 to be associated with social impairment in both an ASD and neurotypical sample.”
BackgroundDavis, C. A., Patte, K. A., Zai, C. C. H., & Kennedy, J. L. (2017) · Nutrition and Diabetes · doi:10.1038/nutd.2017.24 · Cited by 26 · see citing works
Oxytocin and Prader-Willi Syndrome
Kabasakalian, A., Ferretti, C. J., & Hollander, E. (2017) · Current topics in behavioral neurosciences · doi:10.1007/7854_2017_28 · Cited by 26 · see citing works
Evidence for Association Between OXTR Gene and ASD Clinical Phenotypes
Ribeiro, L. D. O. P., Vargas‐Pinilla, P., Kappel, D. B., Longo, D., Ranzan, J., Becker, M. M., Riesgo, R. D. S., Schüler‐Faccini, L., Roman, T., & Schuch, J. B. (2018) · Journal of Molecular Neuroscience · doi:10.1007/s12031-018-1088-0 · Cited by 25 · see citing works
Meyer, M., Kuffner, K., Winter, J. J., Neumann, I. D., Wetzel, C. H., & Jurek, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21062200 · Cited by 26 · see citing works
“As a multifactorial disorder, ASD has been associated with neuronal, morphological and mitochondrial dysfunctions [13–17].”
BackgroundInfluentialSerologic Markers of Autism Spectrum Disorder
Khramova, T., Kaysheva, A. L., Ivanov, Y. D., Pleshakova, T. O., Iourov, I. Y., Vorsanova, S. G., Yurov, Y. B., Schetkin, A. A., & Archakov, A. I. (2017) · Journal of Molecular Neuroscience · doi:10.1007/s12031-017-0950-9 · Cited by 25 · see citing works
“These indicators are more likely related to the individual characteristics of the human body (Parker et al. 2014).”
Huang, M., Liu, K., Wei, Z., Feng, Z., Chen, J., Yang, J., Zhong, Q., Wan, G., & Kong, X. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.721884 · Cited by 28 · see citing works
“Previous studies found that blood OT level is highly correlated with brain OT levels despite inconsistent findings of relative OT levels between children with ASD and healthy children (Modahl et al., 1998; Cochran et al., 2013; Parker et al., 2014; Aita et al., 2019).”
BackgroundRevisiting the wandering womb: Oxytocin in endometriosis and bipolar disorder
Dinsdale, N. L., & Crespi, B. J. (2017) · Hormones and Behavior · doi:10.1016/j.yhbeh.2017.09.005 · Cited by 27 · see citing works
“Autism is characterized by diminished social interest, communication difficulties, and restricted or repetitive interests and behaviours (Cochran et al., 2013), and generally involves reduced activity of the oxytocinergic system (Gordon et al., 2016; Parker et al., 2014).”
BackgroundNew therapeutic options for autism spectrum disorder: experimental evidences
Peñagarikano, O. (2015) · Experimental Neurobiology · doi:10.5607/en.2015.24.4.301 · Cited by 24 · see citing works
“In humans, it has recently been shown that OXT plasma concentration and polymorphisms in the OXT receptor gene drive individual differences in social cognition in both ASD and normal populations [68].”
BackgroundMariscal, M. G., Oztan, O., Rose, S., Libove, R. A., Jackson, L. P., Sumiyoshi, R. D., Trujillo, T. H., Carson, D. S., Phillips, J. M., Garner, J. P., et al. (2019) · Autism Research · doi:10.1002/aur.2135 · Cited by 24 · see citing works
“For example, a previous study found low circulating blood concentrations of OXT to be associated with diminished theory of mind ability, a cognitive form of empathy, in human children [Parker et al., 2014].”
Self-citationWang, J., Braskie, M. N., Hafzalla, G. W., Faskowitz, J., McMahon, K. L., de Zubicaray, G. I., Wright, M. J., Yu, C., & Thompson, P. M. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.12.062 · Cited by 24 · see citing works
Mayer, A. V., Wermter, A.-K., Stroth, S., Alter, P., Haberhausen, M., Stehr, T., Paulus, F. M., Krach, S., & Kamp-Becker, I. (2021) · Scientific Reports · doi:10.1038/s41598-021-94407-x · Cited by 23 · see citing works
The Role of Endogenous Oxytocin in Anxiolysis: Structural and Functional Correlates
Lancaster, K., Goldbeck, L., Pournajafi‐Nazarloo, H., Connelly, J. J., Carter, C. S., & Morris, J. P. (2017) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2017.10.003 · Cited by 23 · see citing works
Social endophenotypes in autism spectrum disorder: A scoping review
Tiede, G., & Walton, K. M. (2020) · Development and Psychopathology · doi:10.1017/s0954579420000577 · Cited by 21 · see citing works
“As one example, oxytocin is a neuropeptide associated with social bonding that has been examined as a potential endophenotype in ASD (Oztan et al., 2018; Parker et al., 2014) and may relate to behaviorally-measured endophenotypes.”
BackgroundMeyer, M., Berger, I., Winter, J. J., & Jurek, B. (2018) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2018.06.013 · Cited by 22 · see citing works
“Here, the functions between OT and MEF-2 may overlap, as both are implicated in autism spectrum disorder (Parker et al., 2014; Bales et al., 2013) and neurite outgrowth (Lestanova et al.”
Chen, Y., Li, Q., Zhang, Q., Kou, J., Zhang, Y., Cui, H., Wernicke, J., Montag, C., Becker, B., Kendrick, K. M., et al. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.589878 · Cited by 23 · see citing works
Wilczyński, K. M., Siwiec, A., & Janas-Kozik, M. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00380 · Cited by 21 · see citing works
“published in 2014 (34), in which the authors conclude that although all studied SNPs were linked to SC deficits across both the study and control groups, they were not associated with ASD itself.”
BackgroundResultInfluentialShang, S., Wu, N., & Su, Y. (2017) · Frontiers in Psychology · doi:10.3389/fpsyg.2017.00396 · Cited by 21 · see citing works
Alaerts, K., Daniëls, N., Moerkerke, M., Evenepoel, M., Tang, T., der Donck, S. V., Chubar, V., Claes, S. J., Steyaert, J. G., Boets, B., et al. (2023) · Psychotherapy and Psychosomatics · doi:10.1159/000534114 · Cited by 20 · see citing works
Zhao, W., Luo, R., Sindermann, C., Li, J., Wei, Z., Zhang, Y., Liu, C., Le, J., Quintana, D. S., Montag, C., et al. (2019) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2019.109734 · Cited by 20 · see citing works
Borie, A. M., Theofanopoulou, C., & Andari, E. (2021) · Handbook of clinical neurology · doi:10.1016/b978-0-12-819973-2.00009-5 · Cited by 18 · see citing works
“Nevertheless, other studies did not find differences in plasma OT levels between ASD and controls, suggesting that the OT system may actually play more of a regulatory role in both the physiology and the pathology (Parker et al., 2014).”
BackgroundAlbantakis, L., Brandi, M., Brückl, T. M., Gebert, D., Auer, M. K., Kopczak, A., Stalla, G. K., Neumann, I. D., & Schilbach, L. (2021) · Comprehensive Psychoneuroendocrinology · doi:10.1016/j.cpnec.2021.100027 · Cited by 19 · see citing works
Makris, G., Chouliaras, G. L., Apostolakou, F., Papageorgiou, C., Chrousos, G. P., Papassotiriou, I., & Pervanidou, P. (2021) · Children · doi:10.3390/children8060478 · Cited by 18 · see citing works
- Authors
- Parker, K. J., Garner, J. P., Libove, R. A., Hyde, S. A., Hornbeak, K. B., Carson, D. S., Liao, C.-P., Phillips, J. M., Hallmayer, J. F., & Hardan, A. Y.
- Affiliations
- Department of Psychiatry and Behavioral Sciences and
- Stanford Medicine (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-08-04
- Volume
- 111
- Issue
- 33
- Pages
- 12258-12263
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4143031
- OpenAlex
- W2093926419
- Cited by
- 215
- References
- 51
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 10 · 2023: 14 · 2022: 23 · 2021: 22 · 2020: 20 · 2019: 18 · 2018: 24 · 2017: 24 · 2016: 19 · 2015: 21 · 2014: 2
- FWCI
- 32.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Research Resources (RR 000167, P51RR000167)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- oxytocin, oxytocin receptor, autism spectrum disorder, OXTR polymorphisms, rs53576, rs2254298, social dysfunction, theory of mind, social communication, affect recognition, heritability, biomarkers, children
- MeSH terms
- Child, Child Development Disorders, Pervasive, Child, Preschool, Female, Humans, Male, Oxytocin, Phenotype, Polymorphism, Genetic, Social Behavior, Case-Control Studies, Receptors, Oxytocin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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