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Cited by 179Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersNeuroendocrine regulation and behavior

Two genetic variants of CD38 in subjects with autism spectrum disorder and controls

Open access
Munesue, Toshio, Yokoyama, Shigeru, Nakamura, Kazuhiko, Anitha, Ayyappan, Yamada, Kazuo, Hayashi, Kenshi, Asaka, Tomoya, Liu, Hong-Xiang +47 more·2010·Neuroscience Research
DOI 10.1016/j.neures.2010.03.004
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Abstract

The neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given the role of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play a role in the etiology of ASD. Here, we first examined the immunohistochemical expression of CD38 in the hypothalamus of post-mortem brains of non-ASD subjects and found that CD38 was colocalized with OT in secretory neurons. In studies of the association between CD38 and autism, we analyzed 10 single nucleotide polymorphisms (SNPs) and mutations of CD38 by re-sequencing DNAs mainly from a case-control study in Japan, and Caucasian cases mainly recruited to the Autism Genetic Resource Exchange (AGRE). The SNPs of CD38, rs6449197 (p<0.040) and rs3796863 (p<0.005) showed significant associations with a subset of ASD (IQ>70; designated as high-functioning autism (HFA)) in the U.S. 104 AGRE family trios, but not with Japanese 188 HFA subjects. A mutation that caused tryptophan to replace arginine at amino acid residue 140 (R140W; (rs1800561, 4693C>T)) was found in 0.6-4.6% of the Japanese population and was associated with ASD in the smaller case-control study. The SNP was clustered in pedigrees in which the fathers and brothers of T-allele-carrier probands had ASD or ASD traits. In this cohort OT plasma levels were lower in subjects with the T allele than in those without. One proband with the T allele who was taking nasal OT spray showed relief of symptoms. The two variant CD38 poloymorphysms tested may be of interest with regard of the pathophysiology of ASD.

AI snapshot

Written from the paper’s full text.

TL;DR

This study examined CD38 variants in autism spectrum disorder (ASD), finding that CD38 colocalizes with oxytocin in human hypothalamic neurons and that two CD38 polymorphisms were associated with high-functioning autism in U.S. AGRE trios but not Japanese HFA trios. A rare R140W mutation was linked to lower plasma oxytocin in a small subset and one carrier reportedly improved on intranasal oxytocin.

Key findings

  • CD38 immunoreactivity colocalized extensively with oxytocin in the paraventricular nucleus of the human hypothalamus; highest CD38 expression was in hypothalamus, with substantial expression in frontal cortex, amygdala, and cerebellum.
  • In U.S. AGRE HFA trios (IQ>70; 104 trios), rs6449197 (p=0.040) and rs3796863 (p=0.005) were significantly associated with ASD; rs3796863 showed only a tendency in all 252 AGRE trios (p=0.088), and no association was detected in 188 Japanese HFA trios (p=0.228). The second haplotype block (SNPs06–07) showed strong association in HFA trios (p=0.001), with the CT haplotype significant after permutation (p=0.005; overtransmitted 69.18%).
  • The R140W mutation (rs1800561, 4693C>T) was found in 0.6%–4.6% of the Japanese population; in cohort 2, 13/301 ASD subjects were heterozygous (allelic frequency 0.022) versus 17/417 controls heterozygous plus one homozygous (allelic frequency 0.023), and the association was not replicated (χ2=1.20, p<0.3). In three families, 18 R140W carriers were identified, 8 of whom had ASD or ASD traits (44%), and no ASD subjects were found without the mutant SNP.
  • Plasma oxytocin was lower in ASD probands with the W140 allele (79.3 ± 14.9 pg/ml; n=3) than in ASD subjects without it (147.7 ± 15.0 pg/ml; p<0.01; n=26) and controls with R140 (198.2 ± 24.7 pg/ml; p<0.01; n=100); AVP was slightly higher in W140 probands (38.9 ± 3.8 vs 26.9 ± 5.0 pg/ml; p<0.05). One 23-year-old proband with the W140 allele received nasal oxytocin and showed maintained improvement for more than 20 months.

Methods

  • Immunohistochemistry and RT-PCR were used on post-mortem human brain tissue to assess CD38 expression and colocalization with oxytocin, including hypothalamic paraventricular nucleus and insular cortex as control.
  • Genetic analyses included 10 intronic SNPs and exonic mutation screening of CD38 across Japanese case-control cohorts (29 ASD/315 controls; 301 ASD/417 controls), 188 Japanese HFA trios, 16 Korean ASD/150 controls, 252 AGRE trios including 104 U.S. HFA trios, plus Russian and Italian samples; analyses used FBAT, TDT, haplotype tests, ANOVA, and permutation.
  • Plasma oxytocin and vasopressin were measured by enzyme immunoassay; ASD traits in relatives were assessed with the Autism-Spectrum Quotient (AQ), and one proband received intranasal oxytocin.

Limitations

  • The paper states “despite their statistical limitations” and calls for functional and expression assays to assess biological effects of the variants, as well as further systematic case-control investigations to verify oxytocin treatment effects.
  • The association findings did not replicate in Japanese HFA trios or in the larger Japanese R140W case-control cohort, and the functional importance of the intronic rs3796863 SNP “remains to be determined.”
  • Evident from the text: plasma oxytocin comparisons for W140 carriers relied on very small numbers (n=3 ASD probands; only one control W140 carrier), the intranasal oxytocin report is a single uncontrolled proband, and the structural analysis is described as preliminary.

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

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Registry

Crossref · 10.1016/j.neures.2010.03.004

Cites

58 of 58 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 22 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In a Japanese case-control study of 29 ASD subjects and 315 controls, no significant association with ASD was found for 10 intronic SNPs.

    “An association study for 10 intronic SNPs shown in Fig. 2 was first performed in a case-control study in a Japanese population (29 ASD subjects and 315 controls, the first cohort in the Table 1).No significant association with ASD was found for these SNPs (data not shown).”
    Quote in the paperSubstantial claim
  • Findingown data

    In 188 Japanese HFA trio cases, no association was detected for the CD38 SNPs tested (p=0.228).

    “Unlike the U.S. cases, no association was detected in 188 Japanese HFA trio cases selected from cohort 2 (p=0.228).”
    Quote in the paperSubstantial claim
  • Findingown data

    LD analysis identified three haplotype blocks across CD38 in 104 AGRE trios.

    “Linkage disequilibrium (LD) analysis identified three haplotype blocks across the CD38 gene in 104 trios in AGRE samples, with the first block comprising SNPs01-05, the second block comprising SNPs06 and 07, and the third block comprising SNPs08 and 09 (Fig. 4).”
    Quote in the paperSubstantial claim
  • Findingown data

    In U.S. 104 AGRE HFA family trios, rs6449197 showed significant association with HFA (p=0.040).

    “In the FBAT of HFA trios, rs6449197 (p=0.040) and rs3796863 (p=0.005)showed significant associations”
    Quote in the paperSubstantial claim
  • Findingown data

    In U.S. 104 AGRE HFA family trios, rs3796863 showed significant association with HFA (p=0.005).

    “In the FBAT of HFA trios, rs6449197 (p=0.040) and rs3796863 (p=0.005)showed significant associations”
    Quote in the paperSubstantial claim
  • May combine two claims. 21
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 14

  • May combine two claims.

    Findingown data

    The highest level of CD38 expression in human brain is in the hypothalamus, with substantial expression in the frontal cortex, amygdala, and cerebellum.

    “The highest level of CD38 expression was detected in the human hypothalamus, and we detected substantial expression in the frontal cortex, amygdala, and cerebellum (data not shown).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    One-way ANOVA showed significant variation in ADI-R_C scores between C/C, C/A, and A/A genotypes of SNP06 in 252 trios (p=0.013) and HFA trios (p=0.0067).

    “One-way ANOVA showed a significant variation in the distribution of ADI-R_C scores (restricted, repetitive, and stereotyped patterns of behavior) between the C/C, C/A, and A/A genotypes of SNP06 of CD38, in 252 trios (p=0.013) and HFA trios (p=0.0067) (Fig. 3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Haplotypes GGCAG (p=0.022) and GGTAG (p=0.034) of the first block showed significant associations, but not by permutation.

    “The haplotypes GGCAG (p=0.022) and GGTAG (p=0.034) of this block showed significant associations; however, this was not significant by permutation (permutation p=0.157 for GGCAG and permutation p=0.271 for GGTAG).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the second block, haplotypes AT (p=0.015) and CT (p=0.0007) showed significant associations; CT remained significant by permutation (p=0.005), while AT did not (p=0.12).

    “In this block, the haplotypes AT (p=0.015) and CT (p=0.0007)showed significant associations; the association shown by CT remained significant (permutation p=0.005), while that of AT was not significant (permutation p=0.12), by permutation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    R140W was detected in 5 of 150 Korean controls but not in 16 Korean patients or 263 Caucasian patients.

    “Furthermore, although we detected the SNP in 5 of the 150 Korean controls, it was not detected it among the 16 Korean patients (cohort 3 in Table 1) or the 263 Caucasian patients (cohort 4 in Table 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The third haploblock including SNPs08 and 09 did not show any association with HFA, and none of the haplotypes in the 252 trios showed significant association.

    “The haplotypes of the 3 rd haploblock, which included SNPs 08 and 09, did not show any association with HFA.None of the haplotypes in the 252 trios showed significant association.”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    One proband with the W140 allele taking nasal OT spray showed relief of symptoms, with quieting on awaking maintained for more than 20 months and improvements in eye contact and answering yes/no questions, without significant adverse effects.

    “The immediate effect of OT was obvious after the first trial, in which he was no longer boisterous after awaking early in the morning.This quieting on awaking has been maintained for more than 20 months.He showed improvements in eye contact behavior with smiling and answering to yes/no questions in his daily life.There were no significant adverse effects.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The mutant structure is more open and has a slightly larger degree of variation.

    “The mutant structure is more open and has a slightly larger degree of variation (Fig. 7C and E).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The W140 mutant CD38 structure has a more open conformation and a slightly larger degree of variation than wild-type CD38.

    “The mutant structure has a more the open conformation than the wild-type and a slightly larger degree of variation.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The predicted protein structures and molecular dynamics simulations accurately reflect the actual structural and dynamic properties of W140-CD38.

  • May combine two claims.

    Findingown data

    The W140 protein has an outward conformation and fewer interacting residues than the wild-type protein.

    “The W140 protein has an outward conformation and fewer interacting residues than the wild-type protein.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The predicted protein structures and molecular dynamics simulations accurately reflect the actual structural and dynamic properties of W140-CD38.

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

    Findingown data

    The amino acid R at position 140 of CD38 is conserved among different species except rodents and rabbits.

    “Amino acid sequence of CD38 showing conservation of R at the 140th amino acid among different species, except for rodents and rabbits.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    R140 and W140 are packed into the helix, and the packing conformation seems stable.

    “R140 and W140 are packed into the helix, and the packing conformation seems stable.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The predicted protein structures and molecular dynamics simulations accurately reflect the actual structural and dynamic properties of W140-CD38.

  • May combine two claims.

    Interpretationreasoning

    The W140 allele is deemed to have a role in decreased plasma OT levels, but not AVP levels, regardless of disease status.

    “However, taking into account the results that the W140 allele is not associated with ASD in general population, we can only say that the W140 allele is deemed to have a role in decreased plasma OT levels, but not in AVP levels, regardless of disease status.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The A allele of rs3796863 may be a protective allele and the C allele a risk allele for U.S. HFA cases.

    “Based on the results of SNP-and haplotype-TDT analyses, the A allele of rs3796863 of CD38 may be considered a protective allele and the C allele as a risk allele for U.S. HFA cases.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    OT is secreted into the brain by hypothalamic neuronal dendrites and plays important roles in social recognition and memory.

    “Oxytocin (OT) is secreted into the brain by hypothalamic neuronal dendrites and plays important roles in social recognition and memory (Insel & Fernald, 2004;Takayanagi et al., 2005;Donaldson et al., 2008;Neumann, 2008).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Insel & Fernald, 2004 source

      Not checked in the free run.

    • cites Takayanagi et al., 2005 source

      Not checked in the free run.

    • cites Donaldson et al., 2008 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Peripheral or nasal administration of OT facilitates social recognition and trust in healthy humans and increases eye contact and recognition in autistic subjects.

    “Peripheral or nasal administration of OT facilitates social recognition and trust in healthy humans (Guastella et al., 2008a andb, 2009;Ditzen et al., 2009) and increases eye contact and recognition in autistic subjects (Hollander et al., 2007;Yamasue et al., 2009).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Guastella et al., 2008a andb, 2009

      Not checked in the free run.

    • cites Ditzen et al., 2009 source

      Not checked in the free run.

    • cites Hollander et al., 2007 source

      Not checked in the free run.

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

    Study design and conductnone given

    The use of control human brain tissue followed institutional guidelines established by the Committee on Human Research in both universities.

    “The use of this tissue followed the institutional guidelines established by the Committee on Human Research (CHR) in both universities.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Diagnoses of ASD were made by two experienced child psychiatrists through interviews and clinical record reviews.

    “The diagnoses were made by two experienced child psychiatrists through interviews and clinical record reviews, and the subjects had no apparent physical anomalies.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    The CD38 gene consists of 8 exons on 4p15 and spans 70.51 kb.

    “The CD38 gene consists of 8 exons on 4p15 (Nakagawa et al., 1995) and spans a genomic stretch of 70.51 kb.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Nakagawa et al., 1995

      Not checked in the free run.

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

    Study design and conductcitation

    Additional selection criteria for AGRE required no possible non-idiopathic autism flags and all trios be Whites, excluding Hispanic and Latino races.

    “Additional selection criteria required that (i) there be no possible non-idiopathic autism flags and (ii) all the trios be Whites, with the exclusion of Hispanic and Latino races (Anita et al., 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Anita et al., 2008

      Not checked in the free run.

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

    Study design and conductnone given

    In the Japanese cohorts, all patients and controls were Japanese with no non-Japanese parents or grandparents.

    “In the Japanese cohorts, all subjects resided in Kanazawa, Hamamatsu/Nagoya, Tokyo, or Osaka, Japan, and all patients and controls were Japanese with no non-Japanese parents or grandparents.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Human CD38 is a type II transmembrane antigen.

    “Human CD38 is a type II transmembrane antigen (Malavasi et al., 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Malavasi et al., 2008 source

      Not checked in the free run.

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

    Premisecitation

    CD38 is expressed in the brain and can catalyze the formation of cADPR from NAD+.

    “CD38 is expressed in the brain (Lee, 2001;Higashida et al., 2007) and can catalyze the formation of cyclic ADP-ribose (cADPR) from NAD + (Lee, 2001;Guse, 2005;Malvasi et al., 2008).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Lee, 2001 source

      Not checked in the free run.

    • cites Guse, 2005 source

      Not checked in the free run.

    • cites Malvasi et al., 2008

      Not checked in the free run.

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

    Study design and conductnone given

    The study was approved by the ethics committees of Kanazawa University, Hamamatsu Medical University, University of Tokyo, Osaka University, RIKEN, and other participating institutes.

    “This study was approved by the ethics committees of Kanazawa University, Hamamatsu Medical University, University of Tokyo, Osaka University, RIKEN, and the other participating institutes.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Two experienced child psychiatrists independently confirmed the diagnosis of ASD for most patients by semi-structured behavior observation and interviews with subjects and parents.

    “Two experienced child psychiatrists independently confirmed the diagnosis of ASD for most patients by semi-structured behavior observation and interviews with the subjects and their parents.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    PedCheck was used to identify and eliminate all Mendelian inheritance inconsistencies in trio genotype data.

    “PedCheck program v1.1 (http://watson.hgen.pitt.edu)was used to identify and eliminate all Mendelian inheritance inconsistencies in the trio genotype data.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    cADPR mobilizes Ca2+ from intracellular stores, acting as a second messenger.

    “cADPR mobilizes Ca 2+ from intracellular Ca 2+ stores, thus acting as a second messenger (Lee, 2001).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Lee, 2001 source

      Not checked in the free run.

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

    Premisecitation

    CD38 regulates OT secretion in the mouse hypothalamus and posterior pituitary, which is critical for mouse social behavior.

    “They showed that CD38 regulates OT secretion in the mouse hypothalamus and posterior pituitary, which is critical for mouse social behavior (Jin et al., 2007;Liu et al., 2008).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Jin et al., 2007 source

      Not checked in the free run.

    • cites Liu et al., 2008 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The rs3796863 SNP may contribute to genetic susceptibility to high-functioning autism in U.S. subjects but not necessarily in Japanese subjects, within the limits of the current analysis.

    “In conclusion, despite their statistical limitations, our results suggest that the rs3796863 SNP may contribute to genetic susceptibility to HFA in U.S. but not necessarily in Japanese subjects (at least to the limits of our current analysis).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The association between rs3796863 and HFA in U.S. trios is not due to population stratification or other confounding that would produce a spurious association.
29 of 29

  • The authors state this as an assumption.

    The precise role of CD38 in the human hypothalamus was not clarified before this study.

    “The precise role of CD38 in the human hypothalamus, however, has not been clarified.”

  • The authors state this as an assumption.

    The effects of long-term OT treatment on human social behavior in ASD patients were unknown before this study.

    “Those observations are based mostly on a small number of administrations, and the effects of long-term OT treatment on human social behavior in ASD patients is unknown.”

  • The paper relies on this without support.

    The unscreened control subjects in cohort 2 were free of ASD.

    “In 417 unscreened control subjects without ASD, 10 males and 7 females were heterozygous for the mutation and one female was homozygous (allelic frequency, 0.023).”

  • The paper relies on this without support.

    The association between rs3796863 and HFA in U.S. trios is not due to population stratification or other confounding that would produce a spurious association.

    “In conclusion, despite their statistical limitations, our results suggest that the rs3796863 SNP may contribute to genetic susceptibility to HFA in U.S. but not necessarily in Japanese subjects (at least to the limits of our current analysis).”

  • The paper relies on this without support.

    The CHO cell and Cd38 null mouse models used in the cited studies are valid models for human W140-CD38 function.

    “In CHO cells, in fact, the W140-CD38 protein possesses only one third of the ADP-ribosyl cyclase activity of R140-CD38 (Yagui et al., 1998).Moreover, social amnesia was not rescued by local re-expression of human W140-CD38 in the hypothalamus in the Cd38 null mice (Jin et al., 2007).”

  • The paper relies on this without support.

    The predicted protein structures and molecular dynamics simulations accurately reflect the actual structural and dynamic properties of W140-CD38.

    “The mutant structure has a more the open conformation than the wild-type and a slightly larger degree of variation.”

  • The paper relies on this without support.

    Low blood oxytocin levels in ASD patients reflect central oxytocin function relevant to social behavior.

    “Furthermore, the W140 allele could be a potential risk factor for a subset of Japanese ASD patients, i.e., males with low blood OT levels.”
7 of 7

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?

  • The R140W mutation causes significant modifications and damage to the predicted protein structure of human CD38.

    “Therefore, the R140W mutation causes significant modifications and damage to the predicted protein structure in comparison with the human wild-type (R140) CD38 (see Fig. 7 of Munesue et al., 2010).”

    From CD38 and its role in oxytocin secretion and social behavior (2012) · cites this paper as Munesue et al., 2010

  • CD38 mRNA is highest in the human hypothalamus.

    “The highest level of CD38 was found in the hypothalamus (Munesue et al., 2010).”

    From CD38 and its role in oxytocin secretion and social behavior (2012) · cites this paper as Munesue et al., 2010

  • A subgroup of ASD subjects with the R140W SNP and intelligence impairments may be effectively treated with OXT.

    “Our preliminary studies suggest that a subgroup of ASD subjects with the R140W SNP and intelligence impairments may be effectively treated with OXT (Munesue et al., 2010)”

    From CD38 and its role in oxytocin secretion and social behavior (2012) · cites this paper as Munesue et al., 2010

  • OXT plasma concentrations of five R140W carriers (79.2 ± 16.6 pg/ml) are lower than those of ASD subjects lacking the mutation (147.7 ± 15.0 pg/ml; p < 0.01; n=26).

    “The OXT plasma concentrations of the five R140W carriers (79.2 ± 16.6 pg/ml; n = 5; Munesue et al., 2010) were lower than those of ASD subjects lacking the mutation (147.7 ± 15.0 pg/ml; p < 0.01; n = 26).”

    From CD38 and its role in oxytocin secretion and social behavior (2012) · cites this paper as Munesue et al., 2010

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.

  • OT sample described as serum in one section and plasma in another

    Minor

    The introduction says the carriers' serum OT levels were measured, but the methods describe separating plasma for the peptide assay, and the results report plasma OT levels. Serum and plasma are different sample types.

1 of 1

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Authors
Munesue, T., Yokoyama, S., Nakamura, K., Anitha, A., Yamada, K., Hayashi, K., Asaka, T., Liu, H.-X., Jin, D., Koizumi, K., Islam, M. S., Huang, J.-J., Ma, W.-J., Kim, U.-H., Kim, S.-J., Park, K., Kim, D., Kikuchi, M., Ono, Y., Nakatani, H., Suda, S., Miyachi, T., Hirai, H., Salmina, A., Pichugina, Y. A., Soumarokov, A. A., Takei, N., Mori, N., Tsujii, M., Sugiyama, T., Yagi, K., Yamagishi, M., Sasaki, T., Yamasue, H., Kato, N., Hashimoto, R., Taniike, M., Hayashi, Y., Hamada, J., Suzuki, S., Ooi, A., Noda, M., Kamiyama, Y., Kido, M. A., Lopatina, O., Hashii, M., Amina, S., Malavasi, F., Huang, E. J., Zhang, J., Shimizu, N., Yoshikawa, T., Matsushima, A., Minabe, Y., & Higashida, H.
Affiliations
  • Kanazawa University (JP)
  • Hamamatsu University (JP)
  • RIKEN Center for Brain Science (JP)
  • Nanao hospital (JP)
  • Korea Advanced Institute of Science and Technology (KR)
Corresponding author
Higashida, Haruhiro
ORCID
Venue
Neuroscience Research
Publisher
Elsevier BV
Published
2010-06
Volume
67
Issue
2
Pages
181-191
ISSN
0168-0102 (ISSN-L)
DOI
10.1016/j.neures.2010.03.004
OpenAlex
W2149724047
Semantic Scholar
add07ecbc7439e42eee6a7ccfffc8035b6731797
Cited by
177
References
59
Citations by year
2026: 3 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 10 · 2019: 10 · 2018: 13 · 2017: 20 · 2016: 12 · 2015: 20 · 2014: 13 · 2013: 20 · 2012: 14
FWCI
10.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuroscience Research (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
  • Kanazawa University Repository for Academic Resources (DSpace) (Kanazawa University) (submittedVersion, cc-by-nc-nd)
Funders
  • San Francisco State University
  • Fondazione Guido Berlucchi
  • University of California, San Francisco
  • Japan Society for the Promotion of Science (22590202, 21791118, 22590772)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
Keywords
CD38, autism spectrum disorder, oxytocin, single nucleotide polymorphisms, high-functioning autism, hypothalamus, social recognition, genetic association, plasma oxytocin, family trios, Japanese population
MeSH terms
Adolescent, Adult, Aged, Analysis of Variance, Brain, Child, Child Development Disorders, Pervasive, Child, Preschool, Cross-Cultural Comparison, Family Health, Female, Gene Frequency, Genotype, Humans, Immunoenzyme Techniques, Japan, Male, Middle Aged, Oxytocin, Vasopressins, Cohort Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, ADP-ribosyl Cyclase 1, Genome-Wide Association Study, Young Adult

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