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Cited by 354Neuroendocrine regulation and behaviorNeurotransmitter Receptor Influence on BehaviorNeuropeptides and Animal Physiology

Oxytocin pathway gene networks in the human brain

Open access
Quintana, Daniel S., Rokicki, Jaroslav, van der Meer, Dennis, Alnæs, Dag, Kaufmann, Tobias, Córdova-Palomera, Aldo, Dieset, Ingrid, Andreassen, Ole A. +1 more·2019·Nature Communications
DOI 10.1038/s41467-019-08503-8PMC PMC6368605

Published version of a preprint

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Abstract

Oxytocin is a neuropeptide involved in animal and human reproductive and social behavior. Three oxytocin signaling genes have been frequently implicated in human social behavior: OXT (structural gene for oxytocin), OXTR (oxytocin receptor), and CD38 (oxytocin secretion). Here, we characterized the distribution of OXT , OXTR , and CD38 mRNA across the human brain by creating voxel-by-voxel volumetric expression maps, and identified putative gene pathway interactions by comparing gene expression patterns across 20,737 genes. Expression of the three selected oxytocin pathway genes was enriched in subcortical and olfactory regions and there was high co-expression with several dopaminergic and muscarinic acetylcholine genes, reflecting an anatomical basis for critical gene pathway interactions. fMRI meta-analysis revealed that the oxytocin pathway gene maps correspond with the processing of anticipatory, appetitive, and aversive cognitive states. The oxytocin signaling system may interact with dopaminergic and muscarinic acetylcholine signaling to modulate cognitive state processes involved in complex human behaviors.

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Written from the paper’s full text.

TL;DR

This study mapped mRNA expression of oxytocin pathway genes (OXT, OXTR, CD38) across the human brain and compared their spatial patterns with all 20,737 protein-coding genes, dopaminergic/cholinergic gene sets, and fMRI-derived cognitive state maps. It reports that OXTR and CD38 are enriched in subcortical/olfactory regions, co-express with dopaminergic and muscarinic acetylcholine genes, and correspond to anticipatory, appetitive, and aversive cognitive states.

Key findings

  • OXTR and CD38 expression was enriched in subcortical and olfactory regions and lower in cerebellum. OXTR was significantly higher than average in olfactory bulbs (p = 0.048, d = 2.1); CD38 was higher in caudate (p = 0.004, d = 4.1), pallidum (p = 0.004, d = 4.6), olfactory bulbs (p = 0.01, d = 3.4), putamen (p = 0.02, d = 2.7), thalamus (p = 0.03, d = 2.1), and anterior cingulate (p = 0.03, d = 2). No brain regions showed significantly higher OXT expression after FDR correction.
  • OXTR and CD38 clustered with DRD2, DRD5, COMT, CHRM4, and CHRM5. A WGCNA module containing OXTR and CD38 (28 genes total) was enriched for waist-hip ratio adjusted for BMI and smoking (p = 1.13 × 10−2), feeding behavior (p = 5.83 × 10−3), cognition (p = 7.44 × 10−3), and behavioral response to stimuli (p = 1.05 × 10−2). The OXTR–CD38 association was significant (p < 0.0001) and in the top 5% of correlations among all 20,737 protein-coding genes.
  • NeuroSynth reverse inference across 14,371 fMRI studies found OXTR expression most correlated with “sexual,” “motivation,” “incentive,” and “anxiety” maps, ranking in the top 0.5% of all 20,737 gene maps (p < 0.001); “taste,” “stress,” “reward,” “monetary,” “fear,” and “emotional” maps were within the top 2.5% (p < 0.001). OXTR (p = 0.0002) and CD38 (p = 0.006) had greater expression in social versus non-social brain regions; OXT did not (p = 0.14).
  • OXTR and CD38 showed high donor-to-donor reproducibility, with differential stability values in the top decile of all 20,737 genes and significant donor-to-donor associations (p < 0.0001). GTEx validation correlated with Allen data for OXTR (rs = 0.81, p = 0.01) and CD38 (rs = 0.67, p = 0.04), but not OXT (rs = 0.22, p = 0.54).

Methods

  • Post-mortem mRNA data came from the Allen Human Brain Atlas: six donor brains (three Caucasian males, one Hispanic female, two African-American males; mean age 42.5 ± 11.2 years; mean post-mortem interval 22.3 ± 4.5 hours), sampled at 363–946 locations per brain. Analyses used left-hemisphere samples, 20,737 protein-coding genes, MNI152 nonlinear registration, and 54 AAL atlas regions; voxel-by-voxel maps were created by Delaunay triangulation and linear interpolation.
  • Independent validation used GTEx data from 10 brain regions (mean sample size 131.7, range 88–173). Analyses included Spearman correlations, complete-linkage clustering, one-sample t-tests with FDR correction across 54 tests, FUMA hypergeometric enrichment, WGCNA (soft-thresholding power 10, scale-free topology R² = 0.828), and NeuroSynth reverse inference with Spearman correlation and 5,000 permutations via PALM.
  • Cognitive state decoding used NeuroSynth release 0.7, extracting text and neuroimaging data from 14,371 fMRI studies; association Z maps were correlated with all 20,737 gene expression maps and ranked.

Limitations

  • Stated: the human post-mortem sample was small and variable in age and ethnicity, with possible variability from brain size and morphology; only one female donor limited comprehensive sex-difference analysis; GTEx has fewer brain sampling sites than Allen; OXT expression was less stable donor-to-donor and not significantly related to GTEx, limiting generalizability for OXT; the study cannot show that increased OXTR transcript expression corresponds to receptor activation during specific cognitive states; several gene–psychiatric disorder links are single-report associations requiring replication.
  • Evident from the design: the work is correlational and cross-sectional, using post-mortem mRNA maps and meta-analytic fMRI associations, so it cannot establish causal or temporal relationships between oxytocin pathway gene expression, dopaminergic/cholinergic signaling, and cognitive states.

Model-written summary. Check it against the paper before relying on it.

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Registry

Crossref · 10.1038/s41467-019-08503-8

Cites

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Statistics

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Claims the paper makes

0 of 79 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    fMRI meta-analysis revealed that the oxytocin pathway gene maps correspond with the processing of anticipatory, appetitive, and aversive cognitive states.

    “fMRI meta-analysis revealed that the oxytocin pathway gene maps correspond with the processing of anticipatory, appetitive, and aversive cognitive states.”
    • Also stated in: § Introduction · hedged
      “The results from a large-scale fMRI meta-analysis suggest that oxytocin pathway gene expression maps correspond with the processing of anticipatory, appetitive, and aversive cognitive states.”
    • Also stated in: § Cognitive state term correlates · plain
      “Decoding cognitive states meta-analytically from voxel-by-voxel mRNA maps (Fig. 6) via quantitative reverse inference revealed that OXTR, CD38, and OXT mRNA expression maps were most highly correlated with functional imaging maps that can be broadly categorized as anticipatory, appetitive, and aversive”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The six donor brains in the Allen Human Brain Atlas are representative of the general human brain for gene expression mapping.
  • Findingown data

    Expression of the three selected oxytocin pathway genes (OXT, OXTR, CD38) is enriched in subcortical and olfactory regions of the human brain.

    “Expression of the three selected oxytocin pathway genes was enriched in subcortical and olfactory regions”
    • Also stated in: § Introduction · plain
      “Expression of critical oxytocin pathway genes are enriched in subcortical and olfactory regions”
    • Also stated in: § Discussion · plain
      “mRNA reflecting specific genes in the oxytocin pathway are highly expressed in subcortical and temporal brain structures, along with the olfactory region.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The six donor brains in the Allen Human Brain Atlas are representative of the general human brain for gene expression mapping.
  • Findingown data

    There is high co-expression of the three oxytocin pathway genes with several dopaminergic and muscarinic acetylcholine genes.

    “there was high co-expression with several dopaminergic and muscarinic acetylcholine genes”
    • Also stated in: § Introduction · plain
      “these genes are highly co-expressed with several dopaminergic and muscarinic acetylcholine genes”
    • Also stated in: § Discussion · plain
      “OXTR and CD38 showed considerable co-expression with DRD2, DRD5, COMT, CHRM4, and CHRM5 genes”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The six donor brains in the Allen Human Brain Atlas are representative of the general human brain for gene expression mapping.
  • Findingown data

    Compared to average expression across the brain, OXTR mRNA levels are statistically significantly higher in the olfactory bulbs (p = 0.048, d = 2.1).

    “Compared to average expression across the brain, statistically significant higher expression of OXTR mRNA levels was observed in the olfactory bulbs (p = 0.048, d = 2.1; Supplementary Data 1).”
    Quote in the paperNot a substantial claim
  • Findingown data

    In both the Allen and GTEx datasets, OXTR, CD38, DRD2, and CHRM4 clustered together.

    “In both datasets, OXTR, CD38, DRD2, and CHRM4 clustered together (Supplementary Fig. 8).”
    Quote in the paperSubstantial claim
  • May combine two claims. 28
  • Classified as probably not a substantial claim. 40

  • May combine two claims.

    Findingown data

    There was significantly lower OXTR expression in the cerebral crus II (p = 0.01, d = 4), cerebellum 7b (p = 0.01, d = 3.6), and cerebellum 8 (p = 0.01, d = 4.3).

    “There was significantly lower OXTR expression in the cerebral crus II (p = 0.01, d = 4), cerebellum 7b (p = 0.01, d = 3.6), and cerebellum 8 (p = 0.01, d = 4.3; Fig. 1a).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Subcortical structures had higher than average expression of OXTR, associated with Cohen's d values >1, but these did not reach FDR corrected thresholds of statistical significance (Pallidum: p = 0.1, d = 1.7; Caudate: p = 0.12, d = 1.5; Putamen: p = 0.13, d = 1.3; Thalamus, p = 0.18, d = 1.1).

    “Subcortical structures had higher than average expression of OXTR, associated with Cohen’s d values >1, but these did not reach FDR corrected (54 tests) thresholds of statistical significance (Pallidum: p = 0.1, d = 1.7; Caudate: p = 0.12, d = 1.5; Putamen: p = 0.13, d = 1.3; Thalamus, p = 0.18, d = 1.1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There was lower CD38 expression in the cerebral crus II (p = 0.045, d = 1.8), cerebellum 7b (p = 0.03, d = 2.1), and cerebellum 8 (p = 0.03, d = 1.9).

    “There was lower CD38 expression in the cerebral crus II (p = 0.045, d = 1.8), cerebellum 7b (p = 0.03, d = 2.1), and cerebellum 8 (p = 0.03, d = 1.9).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    CD38 gene expression was statistically significantly higher than average in the caudate (p = 0.004, d = 4.1), pallidum (p = 0.004, d = 4.6), olfactory bulbs (p = 0.01, d = 3.4), putamen (p = 0.02, d = 2.7), thalamus (p = 0.03, d = 2.1), and cingulate anterior (p = 0.03, d = 2).

    “CD38 gene expression was statistically significantly higher than average in the caudate (p = 0.004, d = 4.1), pallidum (p = 0.004, d = 4.6), olfactory bulbs (p = 0.01, d = 3.4), putamen (p = 0.02, d = 2.7), thalamus (p = 0.03, d = 2.1), and cingulate anterior (p = 0.03, d = 2; Fig. 1b).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Hierarchical clustering revealed that oxytocin pathway genes (OXTR, CD38) cluster with some elements of the dopaminergic (DRD2, DRD5, and COMT) and cholinergic (CHRM4, CHRM5) systems, but not all, indicating the relationship between oxytocin pathway genes and dopaminergic/cholinergic gene sets were not globally strong.

    “Hierarchical clustering revealed that oxytocin pathway genes (OXTR, CD38) cluster with some elements of the dopaminergic (DRD2, DRD5, and COMT) and cholinergic (CHRM4, CHRM5) systems, but not all, indicating the relationship between oxytocin pathway genes and dopaminergic/cholinergic gene sets were not globally strong.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Among the top ten most positive correlations with CD38 were NTSR2 (rs = 0.82), C12orf39 (Spexin; rs = 0.81), and GLUD1 (rs = 0.78).

    “the top ten most positive correlations with CD38 included NTSR2 (rs = 0.82), C12orf39 (Spexin; rs = 0.81), and GLUD1 (rs = 0.78).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The association between OXTR and CD38 was statistically significant (p < 0.0001) and among the top 5% of correlations compared to all 20,737 protein coding genes.

    “The association between OXTR and CD38 was statistically significant (p < 0.0001) and among the top 5% of correlations compared to all 20,737 protein coding genes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Among the top ten most positive mRNA map correlations for OXTR were NTSR2 (rs = 0.78), GLUD2 (rs = 0.78), and GLUD1 (rs = 0.77).

    “Among the top ten most positive mRNA map correlations for OXTR were Neurotensin Receptor 2 (NTSR2; rs = 0.78), Glutamate dehydrogenase 2 (GLUD2; rs = 0.78), and Glutamate dehydrogenase 1 (GLUD1; rs = 0.77)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The gene with the 6th strongest association with CD38 was PSAT1 (rs = 0.79).

    “Additionally, the gene with the 6th strongest association with CD38 was PSAT1 (rs = 0.79), whose disruption has been linked to schizophrenia39.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There was significantly higher expression in the hypothalamic structures compared to the thalamic structures for OXTR (p < 0.001), CD38 (p = 0.002) and OXT (p < 0.001).

    “There was significantly higher expression in the hypothalamic structures compared to the thalamic structures for OXTR (p < 0.001), CD38 (p = 0.002) and OXT (p < 0.001).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    OXTR (p = 0.0002) and CD38 (p = 0.006) had significantly greater mRNA expression in brain regions associated with social behavior compared to brain regions associated with non-social cognitive states.

    “Additionally, OXTR (p = 0.0002; Fig. 7c) and CD38 (p = 0.006; Fig. 7d), had significantly greater mRNA expression in brain regions associated with social behavior compared to brain regions associated with non-social cognitive states (Supplementary Data 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The "taste", "stress", "reward", "monetary", "fear", and "emotional" cognitive state maps were within the top 2.5% of all associations with OXTR expression and also statistically significant (p < 0.001).

    “The “taste”, “stress”, “reward”, “monetary”, “fear”, and “emotional” cognitive state maps were within the top 2.5% of all associations with OXTR expression and also statistically significant (p < 0.001; Fig. 7b; Supplementary Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The OXTR map's relationship with the cognitive state maps of "sexual", "motivation", "incentive", and "anxiety" were all ranked among the top 0.5% strongest associations out of 20,737 genes and were statistically significant (p < 0.001).

    “Notably, the OXTR map’s relationship with the cognitive state maps of “sexual”, “motivation”, “incentive”, and “anxiety” were all ranked among the top 0.5% strongest associations out of 20,737 genes and were statistically significant (p < 0.001; Fig. 7b; Supplementary Table 2)”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    CD38 is involved in oxytocin secretion via Ca2+ release.

    “Specifically, CD38 is involved in oxytocin secretion via Ca2+ release15”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Jin, D. et al. CD38 is critical for social behaviour by regulating oxytocin secretion. Nature 446, 41–45 (2007). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Interactions with the oxytocin system extend beyond the opioid pathway, including the dopaminergic and muscarinic acetylcholine circuits, with possible implications for social behavior and psychiatric disorders.

    “The interactions with the oxytocin system extend beyond the opioid pathway, including the dopaminergic17,18 and muscarinic acetylcholine12,19 circuits, with possible implications for social behavior and psychiatric disorders.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [17] Love, T. M. Oxytocin, motivation and the role of dopamine. Pharmacol. Biochem. Behav. 119, 49–60 (2014). source

      Not checked in the free run.

    • cites [18] Ebstein, R. P., Israel, S., Chew, S. H., Zhong, S. & Knafo, A. Genetics of human social behavior. Neuron 65, 831–844 (2010). source

      Not checked in the free run.

    • cites [12] Loup, F., Tribollet, E., Dubois-Dauphin, M. & Dreifuss, J. Localization of high-affinity binding sites for oxytocin and vasopressin in the human brain. An autoradiographic study. Brain Res 555, 220–232 (1991). source

      Not checked in the free run.

    • cites [19] Freeman, S. M. & Young, L. J. Comparative perspectives on oxytocin and vasopressin receptor research in rodents and primates: translational implications. J. Neuroendocrinol. 28, https://doi.org/10.1111/jne.12382 (2016). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    OXTR mRNA localization in the rodent brain is well-described, but its anatomical distribution across the human brain is poorly understood because investigations have historically sampled very few brain regions.

    “While OXTR mRNA localization in the rodent brain is well-described11, its anatomical distribution across the human brain is poorly understood, as investigations have historically tended to sample very few brain regions12.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [11] Insel, T. R. & Shapiro, L. E. Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles. Proc. Natl Acad. Sci. USA 89, 5981–5985 (1992). source

      Not checked in the free run.

    • cites [12] Loup, F., Tribollet, E., Dubois-Dauphin, M. & Dreifuss, J. Localization of high-affinity binding sites for oxytocin and vasopressin in the human brain. An autoradiographic study. Brain Res 555, 220–232 (1991). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    OXT encodes the oxytocin prepropeptide containing the nonapeptide oxytocin and the carrier protein neurophysin-I.

    “oxytocin-neurophysin I (OXT) encodes the oxytocin prepropeptide containing the nonapeptide oxytocin and the carrier protein neurophysin-I16.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Sausville, E., Carney, D. & Battey, J. The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cancer cell line. J. Biol. Chem. 260, 10236–10241 (1985). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    OXT mRNA is highly expressed in the human paraventricular nucleus of the hypothalamus, the lateral hypothalamic area, and the supraoptic nucleus, and there is evidence of co-expression with OXTR mRNA and the μ and κ types opioid receptor mRNA.

    “OXT mRNA has been shown to be highly expressed in human paraventricular nucleus of the hypothalamus, the lateral hypothalamic area, and the supraoptic nucleus, and there is evidence of co-expression with OXTR mRNA and the μ and κ types opioid receptor mRNA13”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Dal Monte, O. et al. Oxytocin under opioid antagonism leads to supralinear enhancement of social attention. Proc. Natl Acad. Sci. USA 114, 5247–5252 (2017). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    More recent work has examined whole-brain distribution of OXTR genes against a limited set of genes and overexpression in broad functional brain networks, but researchers have yet to explore OXTR's associations with all protein-coding genes or with gene expression patterns associated with specific cognitive states.

    “While more recent work has exclusively examined whole-brain distribution of OXTR genes against a limited set of genes13 and overexpression in broad functional brain networks (e.g., limbic network)14, researchers have yet to explore OXTR’s associations with all protein-coding genes or with gene expression patterns associated with specific cognitive states.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [13] Dal Monte, O. et al. Oxytocin under opioid antagonism leads to supralinear enhancement of social attention. Proc. Natl Acad. Sci. USA 114, 5247–5252 (2017). source

      Not checked in the free run.

    • cites [14] Anderson, K. M. et al. Gene expression links functional networks across cortex and striatum. Nat. Commun. 9, 1428 (2018). source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationcitation

    The spatial distribution of OXTR mRNA corresponds to its functional neuroanatomy and behavioral relevance.

    “suggesting a correspondence between the spatial distribution of OXTR mRNA, its functional neuroanatomy, and behavioral relevance.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    CHRM4 has been associated with schizophrenia and implicated in cognitive flexibility and dopamine release.

    “the muscarinic acetylcholine M4 receptor (CHRM4) has been associated with schizophrenia22 and implicated in cognitive flexibility23 and dopamine release24.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [22] Scarr, E., Sundram, S., Keriakous, D. & Dean, B. Altered hippocampal muscarinic M4, but not M1, receptor expression from subjects with schizophrenia. Biol. Psychiatry 61, 1161–1170 (2007). source

      Not checked in the free run.

    • cites [23] Okada, K. et al. Enhanced flexibility of place discrimination learning by targeting striatal cholinergic interneurons. Nat. Commun. 5, 3778 (2014). source

      Not checked in the free run.

    • cites [24] Grilli, M. et al. Release-enhancing pre-synaptic muscarinic and nicotinic receptors co-exist and interact on dopaminergic nerve endings of rat nucleus accumbens. J. Neurochem. 105, 2205–2213 (2008). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Commonly observed increases in medial and lateral frontal region activity during emotion and pain processing seem to be better explained by more general sustained attention processes.

    “For instance, commonly observed increases in medial and lateral frontal region activity during emotion and pain processing seem to be better explained by more general sustained attention processes27.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Yarkoni, T., Poldrack, R. A., Nichols, T. E., Van Essen, D. C. & Wager, T. D. Large-scale automated synthesis of human functional neuroimaging data. Nat. Methods 8, 665 (2011). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    DRD2 has been implicated in motivational processing and pair bonding in animal models.

    “the dopamine D2-receptor subtype (DRD2), has been implicated in various putative intermediate phenotypes in psychiatric illness, including motivational processing20 and pair bonding in animal models21.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [20] Noble, E. P. D2 dopamine receptor gene in psychiatric and neurologic disorders and its phenotypes. Am. J. Med. Genet. B Neuropsychiatr. Genet. 116, 103–125 (2003). source

      Not checked in the free run.

    • cites [21] Aragona, B. J. et al. Nucleus accumbens dopamine differentially mediates the formation and maintenance of monogamous pair bonds. Nat. Neurosci. 9, 133–139 (2006). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Oxytocin can bind to AVPR1A receptors, which have been linked to social functioning.

    “Finally, oxytocin can also bind to AVPR1A receptors25, which have also been linked to social functioning26.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [25] Cho, M. M., DeVries, A. C., Williams, J. R. & Carter, C. S. The effects of oxytocin and vasopressin on partner preferences in male and female prairie voles (Microtus ochrogaster). Behav. Neurosci. 113, 1071–1079 (1999). source

      Not checked in the free run.

    • cites [26] Bielsky, I. F., Hu, S.-B., Szegda, K. L., Westphal, H. & Young, L. J. Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice. Neuropsychopharmacology 29, 483 (2004). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Brain regions with high oxytocin pathway gene expression in humans have been identified, but inference of specific cognitive states from the activity of single brain regions is elusive.

    “While brain regions with high oxytocin pathway gene expression in humans have been identified12,13, inference of specific cognitive states from the activity of single brain regions is elusive.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [12] Loup, F., Tribollet, E., Dubois-Dauphin, M. & Dreifuss, J. Localization of high-affinity binding sites for oxytocin and vasopressin in the human brain. An autoradiographic study. Brain Res 555, 220–232 (1991). source

      Not checked in the free run.

    • cites [13] Dal Monte, O. et al. Oxytocin under opioid antagonism leads to supralinear enhancement of social attention. Proc. Natl Acad. Sci. USA 114, 5247–5252 (2017). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The NeuroSynth framework has extracted text and neuroimaging data from 14,371 fMRI studies (release 0.7).

    “The NeuroSynth framework27 has extracted text and neuroimaging data from 14,371 fMRI studies (release 0.7).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Yarkoni, T., Poldrack, R. A., Nichols, T. E., Van Essen, D. C. & Wager, T. D. Large-scale automated synthesis of human functional neuroimaging data. Nat. Methods 8, 665 (2011). source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    OXTR and CD38 had differential stability values in the top decile of all 20,737 protein coding genes in the dataset, indicating that gene expression patterning is reproducible, regardless of individual differences, such as ethnicity and sex.

    “We found that both OXTR and CD38 had differential stability values in the top decile of all 20,737 protein coding genes in the dataset (Fig. 5a), indicating that gene expression patterning is reproducible, regardless of individual differences, such as ethnicity and sex.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    NTSR2 has been found to regulate ethanol consumption in mice.

    “NTSR2, which has been found to regulate ethanol consumption in mice35”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Lee, M. R., Hinton, D. J., Unal, S. S., Richelson, E. & Choi, D. S. Increased ethanol consumption and preference in mice lacking neurotensin receptor type 2. Alcohol. Clin. Exp. Res. 35, 99–107 (2011). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    OXT expression did not demonstrate strong whole-brain correspondence with OXTR and CD38 expression, which was likely due to OXT transcripts only showing a strong presence in oxytocin producing cells within hypothalamic regions.

    “OXT expression did not demonstrate strong whole-brain correspondence with OXTR and CD38 expression, which was likely due to OXT transcripts only showing a strong presence in oxytocin producing cells within hypothalamic regions.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    OXTR and CD38 showed considerable co-expression with DRD2, DRD5, COMT, CHRM4, and CHRM5 genes, providing evidence for putative interactions between dopaminergic and muscarinic acetylcholine systems with oxytocin pathway signaling.

    “OXTR and CD38 showed considerable co-expression with DRD2, DRD5, COMT, CHRM4, and CHRM5 genes, providing evidence for putative interactions between dopaminergic and muscarinic acetylcholine systems with oxytocin pathway signaling.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Co-expression of genes across brain regions reflects functional interaction between their signaling systems.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    GLUD1 and GLUD2 are involved in energy homeostasis.

    “GLUD1 and GLUD2, which are involved in energy homeostasis36,37.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [36] Karaca, M. et al. GDH-dependent glutamate oxidation in the brain dictates peripheral energy substrate distribution. Cell Rep. 13, 365–375 (2015). source

      Not checked in the free run.

    • cites [37] Shashidharan, P. & Plaitakis, A. The discovery of human of GLUD2 glutamate dehydrogenase and its implications for cell function in health and disease. Neurochem. Res. 39, 460–470 (2014). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    PSAT1 disruption has been linked to schizophrenia.

    “whose disruption has been linked to schizophrenia39.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Ozeki, Y. et al. A novel balanced chromosomal translocation found in subjects with schizophrenia and schizotypal personality disorder: altered l-serine level associated with disruption of PSAT1 gene expression. Neurosci. Res. 69, 154–160 (2011). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    C12orf39 (Spexin) is associated with weight regulation.

    “C12orf39 (Spexin), with the latter associated with weight regulation38.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Walewski, J. L. et al. Spexin is a novel human peptide that reduces adipocyte uptake of long chain fatty acids and causes weight loss in rodents with diet-induced obesity. Obesity 22, 1643–1652 (2014). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Intranasal oxytocin administration improves appetite regulation in humans.

    “Notably, research indicates that intranasal oxytocin administration improves appetite regulation in humans47,48.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [47] Lawson, E. A. et al. Oxytocin reduces caloric intake in men. Obesity 23, 950–956 (2015). source

      Not checked in the free run.

    • cites [48] Ott, V. et al. Oxytocin reduces reward-driven food intake in humans. Diabetes 62, 3418–3425 (2013). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Emerging evidence points to the oxytocin system's role in energy metabolism, with relevance for metabolic functions.

    “Emerging evidence also points to the oxytocin system’s role in energy metabolism, with relevance for metabolic functions5.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Quintana, D. S., Dieset, I., Elvsåshagen, T., Westlye, L. T. & Andreassen, O. A. Oxytocin system dysfunction as a common mechanism underlying metabolic syndrome and psychiatric symptoms in schizophrenia and bipolar disorders. Front. Neuroendocrinol. 45, 1-–10 (2017). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Intranasal oxytocin has beneficial effects on performance on tests assessing social cognition and gaze to the eye region.

    “Research on humans has shown beneficial effects of intranasal oxytocin on performance on tests assessing social cognition2 and gaze to the eye region3.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [2] Domes, G., Heinrichs, M., Michel, A., Berger, C. & Herpertz, S. C. Oxytocin improves “mind-reading” in humans. Biol. Psychiatry 61, 731–733 (2007). source

      Not checked in the free run.

    • cites [3] Guastella, A. J., Mitchell, P. B. & Dadds, M. R. Oxytocin increases gaze to the eye region of human faces. Biol. Psychiatry 63, 3–5 (2008). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Single nucleotide polymorphisms in oxytocin pathway genes have been associated with social behavior and psychiatric disorders.

    “single nucleotide polymorphisms in oxytocin pathway genes have been associated with social behavior and psychiatric disorders4.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Feldman, R., Monakhov, M., Pratt, M. & Ebstein, R. P. Oxytocin pathway genes: evolutionary ancient system impacting on human affiliation, sociality, and psychopathology. Biol. Psychiatry 79, 174–184 (2016). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    PAK7 and GABRD have been associated with schizophrenia.

    “PAK7 and GABRD which have been associated with schizophrenia49–52.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [49] Morris, D. W. et al. An inherited duplication at the gene p21 Protein-Activated Kinase 7 (PAK7) is a risk factor for psychosis. Hum. Mol. Genet. 23, 3316–3326 (2014). source

      Not checked in the free run.

    • cites [50] Budel, S. et al. Genetic variants of Nogo-66 receptor with possible association to schizophrenia block myelin inhibition of axon growth. J. Neurosci. 28, 13161–13172 (2008). source

      Not checked in the free run.

    • cites [51] Consortium, I. S. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455, 237 (2008). source

      Not checked in the free run.

    • cites [52] Vawter, M. P. et al. Microarray analysis of gene expression in the prefrontal cortex in schizophrenia: a preliminary study. Schizophr. Res. 58, 11–20 (2002). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In rodents, oxytocin receptors are located in regions that are crucial for social behavior and the processing of social cues.

    “In these animals, oxytocin receptors are located in regions that are crucial for social behavior and the processing of social cues11.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Insel, T. R. & Shapiro, L. E. Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles. Proc. Natl Acad. Sci. USA 89, 5981–5985 (1992). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The reported links between specific genes and psychiatric illnesses are largely single-report associations that require replication in independent samples.

    “While these studies suggest intriguing links between specific genes and psychiatric illnesses, it is important to note that these are largely single report associations that require replication in independent samples.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    PSAT1 has been associated with schizophrenia.

    “PSAT1, a gene that has been associated with schizophrenia39.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Ozeki, Y. et al. A novel balanced chromosomal translocation found in subjects with schizophrenia and schizotypal personality disorder: altered l-serine level associated with disruption of PSAT1 gene expression. Neurosci. Res. 69, 154–160 (2011). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    There are reported deficits in dopaminergic signaling in schizophrenia.

    “reported deficits in dopaminergic signaling in schizophrenia60”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] Stopper, C. M. & Floresco, S. B. Dopaminergic circuitry and risk/reward decision making: implications for schizophrenia. Schizophr. Bull. 41, 9–14 (2015). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    There are reported deficits in dopaminergic signaling in autism.

    “This is also congruous with reported deficits in dopaminergic signaling in schizophrenia60 and autism61.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [61] Hettinger, J. A. et al. DRD2 and PPP1R1B (DARPP-32) polymorphisms independently confer increased risk for autism spectrum disorders and additively predict affected status in male-only affected sib-pair families. Behav. Brain Funct. 8, 19 (2012). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The muscarinic acetylcholine system is thought to contribute to the cognitive dysfunction observed in schizophrenia.

    “the muscarinic acetylcholine system is thought to contribute to the cognitive dysfunction observed in schizophrenia64”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] Carruthers, S. P., Gurvich, C. T. & Rossell, S. L. The muscarinic system, cognition and schizophrenia. Neurosci. Biobehav. Rev. 55, 393–402 (2015). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The muscarinic acetylcholine system may assist with the release of oxytocin.

    “and to assist with the release of oxytocin63”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [63] Jankowski, M. et al. Oxytocin and its receptors are synthesized in the rat vasculature. Proc. Natl Acad. Sci. USA 97, 6207–6211 (2000). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The muscarinic acetylcholine system may work with the oxytocin system to boost attention.

    “The muscarinic acetylcholine system may also work with the oxytocin system to boost attention62”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [62] Demeter, E. & Sarter, M. Leveraging the cortical cholinergic system to enhance attention. Neuropharmacology 64, 294–304 (2013). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Central D2 receptors modulate social functioning in prairie voles.

    “central D2 receptors modulate social functioning in prairie voles57”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] Gingrich, B., Liu, Y., Cascio, C., Wang, Z. & Insel, T. R. Dopamine D2 receptors in the nucleus accumbens are important for social attachment in female prairie voles (Microtus ochrogaster). Behav. Neurosci. 114, 173 (2000). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The oxytocin and dopaminergic systems work in concert to promote rodent maternal behaviors.

    “The oxytocin and dopaminergic systems have been shown to work in concert to promote rodent maternal behaviors56”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] Pedersen, C. A., Caldwell, J. D., Walker, C., Ayers, G. & Mason, G. A. Oxytocin activates the postpartum onset of rat maternal behavior in the ventral tegmental and medial preoptic areas. Behav. Neurosci. 108, 1163 (1994). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    Increased mRNA in the human olfactory region may be vestigial.

    “Increased mRNA in the human olfactory region may be vestigial, as olfaction is not as important for human conspecific identification compared to most other mammals due to species specialization”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Olfaction is not as important for human conspecific identification compared to most other mammals due to species specialization.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    These issues, along with individual differences in brain sizes and morphological features, may have introduced variability in sampling.

    “These issues, along with individual differences in brain sizes and morphological features, may have introduced variability in sampling.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Intranasal oxytocin has been shown to improve olfactory detection performance in schizophrenia.

    “intranasal oxytocin has been shown to improve olfactory detection performance in schizophrenia68”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Lee, M. R. et al. Effects of adjunctive intranasal oxytocin on olfactory identification and clinical symptoms in schizophrenia: results from a randomized double blind placebo controlled pilot study. Schizophr. Res. 145, 110–115 (2013). source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductnone given

    The sample size was small and the donor group was variable in age and ethnicity.

    “the sample size was small and the donor group was variable in regards to age and ethnicity.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    High differential stability appears to be a hallmark of genes with considerable biological relevance.

    “high differential stability appears to be a hallmark of genes with considerable biological relevance40.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Hawrylycz, M. et al. Canonical genetic signatures of the adult human brain. Nat. Neurosci. 18, 1832 (2015). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Intranasal oxytocin is thought to enter the brain via the olfactory bulbs.

    “intranasal oxytocin is thought to enter the brain via the olfactory bulbs69”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [69] Quintana, D. S., Guastella, A. J., Westlye, L. T. & Andreassen, O. A. The promise and pitfalls of intranasally administering psychopharmacological agents for the treatment of psychiatric disorders. Mol. Psychiatry 21, 29–38 (2016). source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    The relatively small amount of measurement error for the mRNA probes is indicative of high precision and sufficient generalizability.

    “The relatively small amount of measurement error for the mRNA probes is indicative of high precision and sufficient generalizability.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The GTEx dataset offers less spatial resolution compared to the Allen dataset.

    “Although this dataset offers less spatial resolution compared to the Allen dataset”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Increased OXTR gene expression is associated with increased oxytocin binding.

    “and that increased OXTR gene expression is associated with increased oxytocin binding”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [9] Keebaugh, A. C. & Young, L. J. Increasing oxytocin receptor expression in the nucleus accumbens of pre-pubertal female prairie voles enhances alloparental responsiveness and partner preference formation as adults. Horm. Behav. 60, 498–504 (2011). source

      Not checked in the free run.

    • cites [10] Keebaugh, A. C., Barrett, C. E., Laprairie, J. L., Jenkins, J. J. & Young, L. J. RNAi knockdown of oxytocin receptor in the nucleus accumbens inhibits social attachment and parental care in monogamous female prairie voles. Soc. Neurosci. 10, 561–570 (2015). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Our study may help facilitate efforts to better understand oxytocin treatment efficacy by identifying targets for oxytocin receptor engagement.

    “our study may help facilitate efforts to better understand oxytocin treatment efficacy as it identifies targets for oxytocin receptor engagement, which can facilitate dose-ranging studies69,70.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [69] Quintana, D. S., Guastella, A. J., Westlye, L. T. & Andreassen, O. A. The promise and pitfalls of intranasally administering psychopharmacological agents for the treatment of psychiatric disorders. Mol. Psychiatry 21, 29–38 (2016). source

      Not checked in the free run.

    • cites [70] Insel, T. R. Translating oxytocin neuroscience to the clinic: a National Institute of Mental Health perspective. Biol. Psychiatry 79, 153–154 (2016). source

      Not checked in the free run.

    • Rests on an assumption: Research has not yet demonstrated whether increased OXTR expression in humans is associated with activation of the receptor during specific cognitive states.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The GTEx data is derived from a larger dataset of donors.

    “the data is derived from a larger dataset of donors (mean sample size for mRNA expression across brain regions = 131.7, range = 88 to 173).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The collection of human data complied with relevant ethical regulations, with institutional review board approval obtained at each tissue bank and repository that provided tissue samples.

    “The collection of human data complied with relevant ethical regulations, with institutional review board approval obtained at each tissue bank and repository that provided tissue samples.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Animal models demonstrate that OXTR expression levels directly modulate social behavior.

    “animal models demonstrating that OXTR expression levels directly modulate social behavior9,10”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [9] Keebaugh, A. C. & Young, L. J. Increasing oxytocin receptor expression in the nucleus accumbens of pre-pubertal female prairie voles enhances alloparental responsiveness and partner preference formation as adults. Horm. Behav. 60, 498–504 (2011). source

      Not checked in the free run.

    • cites [10] Keebaugh, A. C., Barrett, C. E., Laprairie, J. L., Jenkins, J. J. & Young, L. J. RNAi knockdown of oxytocin receptor in the nucleus accumbens inhibits social attachment and parental care in monogamous female prairie voles. Soc. Neurosci. 10, 561–570 (2015). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Informed consent was provided by each donor's next-of-kin.

    “informed consent was provided by each donor’s next-of-kin.”
    Quote in the paperNot a substantial claim
62 of 62

  • The paper relies on this without support.

    Co-expression of genes across brain regions reflects functional interaction between their signaling systems.

    “reflecting an anatomical basis for critical gene pathway interactions”
    “providing evidence for putative interactions between dopaminergic and muscarinic acetylcholine systems with oxytocin pathway signaling.”

  • The paper relies on this without support.

    The mRNA co-expression of dopaminergic, muscarinic acetylcholine, and other systems with the oxytocin system is not well characterized.

    “However, the mRNA co-expression of these systems, and potentially others, with the oxytocin system is not well characterized.”

  • The paper relies on this without support.

    The six donor brains in the Allen Human Brain Atlas are representative of the general human brain for gene expression mapping.

    “The full dataset of protein coding genes (n = 20,737) from six donor brains were collected from the Allen Human Brain Atlas (http://human.brain-map.org/).”
    “Here, we leveraged the unique human brain mRNA expression library from Allen Brain Atlas to show that mRNA reflecting specific genes in the oxytocin pathway are highly expressed in subcortical and temporal brain structures, along with the olfactory region.”

  • The paper relies on this without support.

    Olfaction is not as important for human conspecific identification compared to most other mammals due to species specialization.

    “as olfaction is not as important for human conspecific identification compared to most other mammals due to species specialization”

  • The paper relies on this without support.

    Research has not yet demonstrated whether increased OXTR expression in humans is associated with activation of the receptor during specific cognitive states.

    “research is yet to demonstrate whether the increased expression of OXTR (as measured by the presence of its transcript) in humans is associated with the activation of the receptor during specific cognitive states.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In humans, OXTR mRNA is detected in the nucleus accumbens.

    “OXTR mRNA has been detected in the nucleus accumbens (Bethlehem et al. 2017; Quintana et al. 2019)”

    From Distribution of brain oxytocin and vasopressin V1a receptors in chimpanzees (Pan troglodytes): comparison with humans and other primate species (2022) · cites this paper as Quintana et al. 2019

  • There is strong correlation between the expression of OXTR and dopamine receptors (especially D2R) and muscarinic acetylcholine receptors.

    “Additionally, there is strong correlation between the expression of the oxytocin receptor gene (OXTR) and dopamine receptors (especially D2R) and muscarinic acetylcholine receptors.”

    From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [31]

  • Quintana et al. mapped the mRNA of oxytocin pathway genes throughout human brains and found the highest expression in olfactory bulbs and pallidum, high expression in hypothalamus, thalamus, caudate, and putamen, and more moderately elevated expression in amygdala, anterior cingulum, and hippocampus.

    “Quintana et al. [31] mapped the mRNA of oxytocin pathway genes throughout human brains and found the highest expression in olfactory bulbs and pallidum, high expression in hypothalamus, thalamus, caudate, and putamen, and more moderately elevated expression in amygdala, anterior cingulum, and hippocampus.”

    From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [31]

  • Comparing OXTR expression and fMRI activity associated with cognitive states revealed a robust correlation between OXTR expression and activity maps for "sexual", "motivation", "incentive", and "anxiety" cognitive states.

    “Comparing OXTR expression and fMRI activity associated with cognitive states revealed a robust correlation between OXTR expression and activity maps for “sexual”, “motivation”, “incentive”, and “anxiety” cognitive states.”

    From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [31]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • GTEx validation describes 11 regions as 10

    Minor

    The independent-sample validation says it used 10 distinct brain regions, but the parenthetical list names 11.

1 of 1

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Related

Authors
Quintana, D. S., Rokicki, J., van der Meer, D., Alnæs, D., Kaufmann, T., Córdova-Palomera, A., Dieset, I., Andreassen, O. A., & Westlye, L. T.
Affiliations
Oslo University Hospital (NO)
Corresponding author
Quintana, Daniel S.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-02-08
Volume
10
Issue
1
Pages
668-668
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-08503-8
PMC
PMC6368605
OpenAlex
W2912308393
Semantic Scholar
ba7f26bd71b739a813a7340a6e765b4b799bc092
Cited by
354
References
76
Citations by year
2026: 27 · 2025: 31 · 2024: 43 · 2023: 43 · 2022: 41 · 2021: 78 · 2020: 74 · 2019: 16 · 2018: 1
FWCI
65.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • OSF Preprints (OSF Preprints) (submittedVersion)
  • OSF Preprints (OSF Preprints) (submittedVersion, cc-by)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
Funders
  • Novo Nordisk (NNF16OC0019856)
  • Norges Forskningsråd (223273, #249795)
  • Novo Nordisk Fonden (NNF16OC0019856)
  • Helse Sør-Øst RHF (#2014-097, 2015-073, 223273, 2017–112)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
oxytocin signaling, oxytocin receptor, CD38, gene co-expression network, subcortical structures, olfactory region, dopaminergic signaling, cognitive states, social behavior, reproductive behavior
MeSH terms
Adult, Brain, Cognition, Female, Humans, Hypothalamus, Magnetic Resonance Imaging, Male, Middle Aged, Oxytocin, RNA, Messenger, Receptors, Oxytocin, ADP-ribosyl Cyclase 1

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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