Altered Chemical Metabolites in the Amygdala-Hippocampus Region Contribute to Autistic Symptoms of Autism Spectrum Disorders

Endo, Toshiya; Shioiri, Toshiki; Kitamura, Hiroyuki; Kimura, Teruo; Endo, Sumio; Masuzawa, Naio; Someya, Toshiyuki

doi:10.1016/j.biopsych.2007.05.015

Cited by 75 publications

(52 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2 We genotyped 14 single nucleotide polymorphisms (SNP) in OXTR using the TaqMan 5′-exonuclease assay.…”

mentioning

confidence: 99%

“…1 Our previous study showed a decrease in relative ratios of N-acetylaspartate to creatine (NAA/Cr) in the right medial temporal lobe (MTL) in ASD individuals. 2 Here, we investigated the effects of OXTR on right MTL NAA/Cr in ASD individuals.…”

mentioning

confidence: 99%

“…DNA samples were taken from 26 ASD individuals (21 boys and five girls; mean age = 13.1 ± 3.6 years) who overlapped with those in our previous study. 2 Detailed protocol for proton magnetic resonance spectroscopy has been previously described. 2 We genotyped 14 single nucleotide polymorphisms (SNP) in OXTR using the TaqMan 5′-exonuclease assay.…”

mentioning

confidence: 99%

“…2 Detailed protocol for proton magnetic resonance spectroscopy has been previously described. 2 We genotyped 14 single nucleotide polymorphisms (SNP) in OXTR using the TaqMan 5′-exonuclease assay. 3 We compared mean right MTL NAA/Cr between major allele homozygotes and minor allele carriers of each SNP using ANCOVA with age 4 and full-scale IQ as covariates.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Possible association between the oxytocin receptor gene and N‐acetylaspartate of the right medial temporal lobe in autism spectrum disorders

Egawa

Watanabe

Endo

et al. 2013

Psychiatry Clin Neurosci

Self Cite

View full text Add to dashboard Cite

O XYTOCIN (OXT) SIGNALING THROUGH its receptor (OXTR) has been implicated in the pathophysiology of autism spectrum disorders (ASD).1 Our previous study showed a decrease in relative ratios of N-acetylaspartate to creatine (NAA/Cr) in the right medial temporal lobe (MTL) in ASD individuals.2 Here, we investigated the effects of OXTR on right MTL NAA/Cr in ASD individuals.This study was approved by the Ethics Committee on Genetics of the Niigata University School of Medicine. All participants and their parents provided written informed consent. DNA samples were taken from 26 ASD individuals (21 boys and five girls; mean age = 13.1 ± 3.6 years) who overlapped with those in our previous study.2 Detailed protocol for proton magnetic resonance spectroscopy has been previously described. 2 We genotyped 14 single nucleotide polymorphisms (SNP) in OXTR using the TaqMan 5′-exonuclease assay.3 We compared mean right MTL NAA/Cr between major allele homozygotes and minor allele carriers of each SNP using ANCOVA with age 4 and full-scale IQ as covariates. Power calculations were performed using G*Power v3.1.7 (http://www.psycho.uni-duesseldorf.de/ abteilungen/aap/gpower3).We observed nominally significant differences in mean NAA/Cr in the right MTL, including the amygdalahippocampus region, between major allele homozygotes and minor allele carriers of two SNP: 1.14 ± 0.23 and 1.40 ± 0.21, respectively (P = 0.010) for rs9840864; and 1.18 ± 0.27 and 1.41 ± 0.18, respectively (P = 0.020) for rs11706648.Our study is in line with earlier studies reporting an association between OXTR and neuroimaging indices for the amygdala and hippocampus. 1There are some limitations of the present study. First, the associations between two SNP and the right MTL NAA/Cr did not survive a multiple testing correction. Sixty-two samples are needed to detect the associations with an α of 0.0036 (0.05/ 14) and a power of 0.8, under the favorable assumption that the effect size d is 1.0 and the numbers of each group are equal. Second, we used a ratio rather than absolute quantification of neurochemical metabolites. As such, we cannot determine whether NAA/Cr variation by the genetic polymorphisms was due to an alteration of NAA or Cr concentration.In conclusion, our findings obtained from an imaginggenetics approach provided preliminary evidence for the association between OXTR and neuronal function in the MTL in ASD individuals. Advances in such an approach appear to be promising for understanding ASD with diverse causes.

show abstract

“…2 We genotyped 14 single nucleotide polymorphisms (SNP) in OXTR using the TaqMan 5′-exonuclease assay.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Possible association between the oxytocin receptor gene and N‐acetylaspartate of the right medial temporal lobe in autism spectrum disorders

Egawa

Watanabe

Endo

et al. 2013

Psychiatry Clin Neurosci

Self Cite

View full text Add to dashboard Cite

show abstract

“…The participants were 32 Japanese male patients between 6 and 20 years of age, who met the DSM-IV criteria for autistic disorder (n = 10), Asperger's disorder (n = 12) or pervasive developmental disorder not otherwise specified (n = 10). 1,3 Each participant was assessed using the childhood autistic rating scale -Tokyo version, the Wechsler Intelligence Scale for Children -Third Edition or the Wechsler Adult Intelligence Scale -Revised, and the Edinburgh Handedness Inventory. Details of the procedure for magnetic resonance image acquisition and brain volume measurements have been described elsewhere.…”

mentioning

confidence: 99%

Reduced thalamus volume in non‐right‐handed male patients with autism spectrum disorders

Egawa¹,

Watanabe

Kitamura³

et al. 2011

Psychiatry Clin Neurosci

Self Cite

View full text Add to dashboard Cite

Increased Glutamate Concentration in the Auditory Cortex of Persons With Autism and First‐Degree Relatives: A ¹H‐MRS Study

Brown¹,

Singel²,

Hepburn³

et al. 2012

Autism Research

123

105

View full text Add to dashboard Cite

Lay Abstract We investigated brain chemistry of the primary region of the brain involved in auditory processing in adults with autism spectrum disorder (ASD). Due to the highly heritable nature of ASD and the lack of prior brain chemistry data on unaffected first-degree relatives, we also enrolled parents of children with ASD (pASD), comparing both groups to a healthy adult control group. The technique used to quantify chemical signals was magnetic resonance spectroscopy (MRS), which we used to assess the concentration of auditory glutamate, the primary excitatory brain neurotransmitter, as well as other metabolites that assess neuronal integrity and metabolism. We found significantly higher levels of auditory glutamate in persons with ASD. In addition, increases in two other metabolites, n-acetyl-aspartate (NAA), and creatine (Cr), were observed in the ASD group. No differences were observed in the pASD group in any MRS measurement. We interpret the glutamate finding as suggestive of an increase in brain excitability, and the NAA and Cr findings as indicative of a change in brain energy metabolism in ASD. Scientific Abstract Increased glutamate levels have been reported in the hippocampal and frontal regions of persons with autism using proton magnetic resonance spectroscopy (1H-MRS). Although autism spectrum disorders (ASD) are highly heritable, MRS studies have not included relatives of persons with ASD. We therefore conducted a study to determine if glutamate levels are elevated in people with autism and parents of children with autism. Single-voxel, point resolved spectroscopy (PRESS) data were acquired at 3T for left and right hemisphere auditory cortical voxels in 13 adults with autism, 15 parents of children with autism, and 15 adult control subjects. The primary measure was Glx. Additional measures included n-acetyl-aspartate (NAA), choline (Cho), myoinositol (mI) and creatine (Cr). The autism group had significantly higher Glx, NAA and Cr concentrations than the control subjects. Parents did not differ from control subjects on any measures. No significant differences in Cho or mI levels were seen among groups. No reliable correlations between autism symptom measures and MRS variables were seen after Bonferroni correction for multiple comparisons. The elevation in Glx in autism is consistent with prior MRS data in the hippocampus and frontal lobe and may suggest increased cortical excitability. Increased NAA and Cr may indicate brain metabolism disturbances in autism. In the current study, we found no reliable evidence of a familial effect for any spectroscopy measure. This may indicate that these metabolites have no heritable component in autism, the presence of a compensatory factor in parents, or sample specific limitations such the participation of singleton families.

show abstract

Altered Chemical Metabolites in the Amygdala-Hippocampus Region Contribute to Autistic Symptoms of Autism Spectrum Disorders

Cited by 75 publications

References 50 publications

Possible association between the oxytocin receptor gene and N‐acetylaspartate of the right medial temporal lobe in autism spectrum disorders

Possible association between the oxytocin receptor gene and N‐acetylaspartate of the right medial temporal lobe in autism spectrum disorders

Reduced thalamus volume in non‐right‐handed male patients with autism spectrum disorders

Increased Glutamate Concentration in the Auditory Cortex of Persons With Autism and First‐Degree Relatives: A ¹H‐MRS Study

Contact Info

Product

Resources

About

Altered Chemical Metabolites in the Amygdala-Hippocampus Region Contribute to Autistic Symptoms of Autism Spectrum Disorders

Cited by 75 publications

References 50 publications

Possible association between the oxytocin receptor gene and N‐acetylaspartate of the right medial temporal lobe in autism spectrum disorders

Possible association between the oxytocin receptor gene and N‐acetylaspartate of the right medial temporal lobe in autism spectrum disorders

Reduced thalamus volume in non‐right‐handed male patients with autism spectrum disorders

Increased Glutamate Concentration in the Auditory Cortex of Persons With Autism and First‐Degree Relatives: A 1H‐MRS Study

Contact Info

Product

Resources

About

Increased Glutamate Concentration in the Auditory Cortex of Persons With Autism and First‐Degree Relatives: A ¹H‐MRS Study