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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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“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]
In the citing paper
“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]
In the citing paper
“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
In the citing paper
“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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The oxytocin receptor: from intracellular signaling to behavior
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“Biomarker and genetic data for OT and its receptor have been promising but inconsistent in ASD and in relation to various measures of human social behavior (Modahl et al., 1998, Jacob et al., 2007, Hammock et al., 2012, Miller et al., 2013a, Parker et al., 2014, Skuse et al., 2014).”
BackgroundExogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism
Peñagarikano, O., Lázaro, M. T., Lu, X.-H., Gordon, A., Dong, H., Lam, H. A., Peles, E., Maidment, N. T., Murphy, N. P., Yang, X. W., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.3010257 · Cited by 378
Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism
Parker, K. J., Oztan, O., Libove, R. A., Sumiyoshi, R. D., Jackson, L. P., Karhson, D. S., Summers, J. E., Hinman, K. E., Motonaga, K. S., Phillips, J. M., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705521114 · Cited by 349
“Because idiopathic ASD is characterized by enormous heterogeneity, including substantial variability in blood OXT concentrations (27), we hypothesized that the prior ambiguous OXT clinical trial findings might be attributable, at least in part, to variability in participants’ pretreatment neuropeptide biology.”
BackgroundMethodInfluentialSelf-citationMarotta, R., Risoleo, M. C., Messina, G., Parisi, L., Carotenuto, M., Vetri, L., & Roccella, M. (2020) · Brain Sciences · doi:10.3390/brainsci10030163 · Cited by 279
“An association between the degree of methylation of the oxytocin receptor (OXTR) gene and autistic symptoms has been reported [112,113].”
BackgroundQuintana, D. S., Lischke, A., Grace, S., Scheele, D., Ma, Y., & Becker, B. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00864-7 · Cited by 263
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“In humans, some studies suggest genetic variability in the OXTR gene could increase risk for autism (49-52, 54), but others show associations reflecting broader social-cognitive phenotypes (55-58).”
Baribeau, D. A., & Anagnostou, E. A. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00335 · Cited by 241
“Oxytocin and AVPR1a binding was detected in numerous limbic and autonomic pathways, with some distinct areas and some overlapping.”
BackgroundInfluentialPuglia, M. H., Lillard, T. S., Morris, J. P., & Connelly, J. J. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1422096112 · Cited by 216
“However, establishing direct links between oxytocin levels and specific social abilities has proven difficult, and the majority of studies have mixed results (18, 19).”
ResultCarson, D. S., Berquist, S. W., Trujillo, T. H., Garner, J. P., Hannah, S. L., Hyde, S. A., Sumiyoshi, R. D., Jackson, L. P., Moss, J. K., Strehlow, M. C., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.132 · Cited by 196
Self-citationKing, L. B., Walum, H., Inoue, K., Eyrich, N. W., & Young, L. J. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.12.008 · Cited by 191
“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).”
InfluentialYoung, L. J., & Barrett, C. E. (2015) · Science · doi:10.1126/science.aaa8120 · Cited by 200
Advances in human oxytocin measurement: challenges and proposed solutions
Tabak, B. A., Leng, G., Szeto, A., Parker, K. J., Verbalis, J. G., Ziegler, T. E., Lee, M. R., Neumann, I. D., & Mendez, A. J. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01719-z · Cited by 170
“There may be certain human populations that require fewer assessments to reliably index basal oxytocin levels [19, 94].”
BackgroundSelf-citationOxytocin and Social Relationships: From Attachment to Bond Disruption
Bosch, O. J., & Young, L. J. (2017) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2017_10 · Cited by 162
“…that polymorphisms in the human OTR predict not only social behavioral phenotypes, including those associated with autism (Skuse et al. 2014; Parker et al. 2014; LoParo and Waldman 2015), but also how early-life experiences shape later psychiatric outcomes (Schneider-Hassloff et al. 2016;…”
BackgroundKeebaugh, A. C., Barrett, C. E., Laprairie, J. L., Jenkins, J. J., & Young, L. J. (2015) · Social Neuroscience · doi:10.1080/17470919.2015.1040893 · Cited by 150
“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.”
BackgroundInfluentialPlasma anandamide concentrations are lower in children with autism spectrum disorder
Karhson, D. S., Krasinska, K. M., Dallaire, J. A., Libove, R. A., Phillips, J. M., Chien, A., Garner, J. P., Hardan, A. Y., & Parker, K. J. (2018) · Molecular Autism · doi:10.1186/s13229-018-0203-y · Cited by 159
“Participants had been recruited as part of a previous study to investigate blood biomarkers and genetic variants in children with ASD [10].”
MethodSelf-citationIntranasal oxytocin, social cognition and neurodevelopmental disorders: A meta-analysis
Keech, B., Crowe, S., & Hocking, D. R. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.09.022 · Cited by 145
“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].”
BackgroundOxytocin modulation of neural circuits for social behavior
Marlin, B. J., & Froemke, R. C. (2017) · Developmental Neurobiology · doi:10.1002/dneu.22452 · Cited by 130
“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).”
BackgroundInterpersonal Synchrony in Autism
McNaughton, K. A., & Redcay, E. (2020) · Current Psychiatry Reports · doi:10.1007/s11920-020-1135-8 · Cited by 133
Overview of human oxytocin research
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Introducing Therioepistemology: the study of how knowledge is gained from animal research
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Self-citationThe interplay of hypoxic and mental stress: Implications for anxiety and depressive disorders
Burtscher, J., Niedermeier, M., Hüfner, K., van den Burg, E. H., Kopp, M., Stoop, R., Burtscher, M., Gatterer, H., & Millet, G. P. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104718 · Cited by 109
“, 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
John, S., & Jaeggi, A. V. (2021) · Autism · doi:10.1177/13623613211034375 · Cited by 105
“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…”
BackgroundResultInfluentialPriel, A., Djalovski, A., Zagoory‐Sharon, O., & Feldman, R. (2018) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12880 · Cited by 106
Cataldo, I., Azhari, A., & Esposito, G. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00027 · Cited by 97
“Besides autism, rs2254298 was also linked to social impairment in general (Parker et al., 2014), empathy (Wu et al.”
BackgroundInfluentialDetection, processing and reinforcement of social cues: regulation by the oxytocin system
Menon, R., & Neumann, I. D. (2023) · Nature Reviews Neuroscience · doi:10.1038/s41583-023-00759-w · Cited by 100
Insular function in autism: Update and future directions in neuroimaging and interventions
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“…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 94
Autism Biomarkers: Challenges, Pitfalls and Possibilities
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“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).”
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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 88
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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
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 73
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
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
“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 62
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 61
“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 62
“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 62
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 63
“…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
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 58
Oxytocin in animal models of autism spectrum disorder
Peñagarikano, O. (2016) · Developmental Neurobiology · doi:10.1002/dneu.22449 · Cited by 56
“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
Kohlhoff, J. R., Cibralic, S., Hawes, D. J., & Eapen, V. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104573 · Cited by 53
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 54
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
“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 52
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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
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
“, 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
“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 51
McDonald, N. M., Baker, J. K., & Messinger, D. S. (2016) · Developmental Psychology · doi:10.1037/dev0000104 · Cited by 43
“, 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
“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
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 42
“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 43
“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 42
“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 39
“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
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 38
“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
“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
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
Oxytocin: A citation network analysis of 10 000 papers
Leng, G., & Leng, R. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.13014 · Cited by 34
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 32
“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 33
“, 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 32
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 39
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 31
“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
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 30
“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
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 28
“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
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
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 26
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
“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
“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
“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
“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
“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
“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
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
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 24
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
“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
“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 26
Wilczyński, K. M., Siwiec, A., & Janas-Kozik, M. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00380 · Cited by 21
“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 22
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 21
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
Borie, A. M., Theofanopoulou, C., & Andari, E. (2021) · Handbook of clinical neurology · doi:10.1016/b978-0-12-819973-2.00009-5 · Cited by 19
“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
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
Metadata
- 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
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › 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
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