Brief Report: Biochemical Correlates of Clinical Impairment in High Functioning Autism and Asperger’s Disorder

Kleinhans, Natalia M.; Richards, Todd L.; Weaver, Kurt E.; Liang, Olivia; Dawson, Geraldine; Aylward, Elizabeth H.

doi:10.1007/s10803-009-0707-6

Cited by 24 publications

(25 citation statements)

References 40 publications

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“…Although the majority of MRS studies have reported lower NAA in at least one studied region in autism (Chugani, Sundram, Behen, Lee, & Moore, 1999; DeVito, et al, 2007; Endo et al, 2007; Friedman et al, 2006; Gabis et al, 2008; Hardan, et al, 2008; Hisaoka, Harada, Nishitani, & Mori, 2001; Levitt et al, 2003; Otsuka, et al, 1999), this is not a universal finding among regions even within the same study. To our knowledge, higher NAA has been reported in only one prior study (Murphy et al, 2002), although other studies do not find NAA differences between ASD and comparison groups (Bernardi, et al, 2011; Harada, et al, 2010; Kleinhans et al, 2009; Page, et al, 2006; Vasconcelos et al, 2008; Zeegers, van der Grond, van Daalen, Buitelaar, & van Engeland, 2007). Ages of participants are widely variable among the published studies, but could also potentially contribute to the mixed findings for NAA, as NAA (NAA/Cr and NAA/Cho) is reported to increase dramatically from 1 month to 3 years, with changes observed until 16 years (van der Knaap et al, 1990).…”

Section: Discussioncontrasting

confidence: 63%

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

119

105

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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.

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Section: Discussioncontrasting

confidence: 63%

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

119

105

View full text Add to dashboard Cite

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“…Neuroimaging of metabolic activity in regions implicated in ASD was able to distinguish ASD cases with and without language impairment [Gabis et al, 2008]. Recently, Kleinhans et al [2009] showed positive correlation of IQ and neurometabolites in the amygdala region of high‐functioning ASD patients. As this work is preliminary, there are presently no laboratory tests specific to the ASP diagnosis or that differentiate clinical subgroups.…”

Section: Introductionmentioning

confidence: 99%

Variants in several genomic regions associated with asperger disorder

Salyakina

Jaworski

et al. 2010

Autism Research

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Asperger disorder (ASP) is one of the autism spectrum disorders (ASD) and is differentiated from autism largely on the absence of clinically significant cognitive and language delays. Analysis of a homogenous subset of families with ASP may help to address the corresponding effect of genetic heterogeneity on identifying ASD genetic risk factors. To examine the hypothesis that common variation is important in ASD, we performed a genome-wide association study (GWAS) in 124 ASP families in a discovery data set and 110 ASP families in a validation data set. We prioritized the top 100 association results from both cohorts by employing a ranking strategy. Novel regions on 5q21.1 (P = 9.7 × 10−7) and 15q22.1–q22.2 (P = 7.3 × 10−6) were our most significant findings in the combined data set. Three chromosomal regions showing association, 3p14.2 (P = 3.6 × 10−6), 3q25–26 (P = 6.0 × 10−5) and 3p23 (P = 3.3 × 10−4) overlapped linkage regions reported in Finnish ASP families, and eight association regions overlapped ASD linkage areas. Our findings suggest that ASP shares both ASD-related genetic risk factors, as well as has genetic risk factors unique to the ASP phenotype.

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“…The comparison of the results from these different studies is impeded for a number of reasons. Some authors examined the amygdala of children, where at least lower tNAA and higher tCho than in adults may be expected . Furthermore, none of the previously reported results has been obtained with a measured MM baseline.…”

Section: Discussionmentioning

confidence: 97%

Towards a neurochemical profile of the amygdala using short‐TE ¹H magnetic resonance spectroscopy at 3 T

et al. 2017

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The amygdala plays a key role in emotional learning and in the processing of emotions. As disturbed amygdala function has been linked to several psychiatric conditions, a knowledge of its biochemistry, especially neurotransmitter levels, is highly desirable. The spin echo full intensity acquired localized (SPECIAL) sequence, together with a transmit/receive coil, was used to perform very short-TE magnetic resonance spectroscopy at 3 T to determine the neurochemical profile in a spectroscopic voxel containing the amygdala in 21 healthy adult subjects. For spectral analysis, advanced data processing was applied in combination with a macromolecule baseline measured in the anterior cingulate for spectral fitting. The concentrations of total N-acetylaspartate, total creatine, total choline, myo-inositol and, for the first time, glutamate were quantified with high reliability (uncertainties far below 10%). For these metabolites, the inter-individual variability, reflected by the relative standard deviations for the cohort studied, varied between 12% (glutamate) and 22% (myo-inositol). Glutamine and glutathione could also be determined, albeit with lower precision. Retest on four subjects showed good reproducibility. The devised method allows the determination of metabolite concentrations in the amygdala voxel, including glutamate, provides an estimation of glutamine and glutathione, and may help in the study of disturbed amygdala metabolism in pathologies such as anxiety disorder, autism and major depression.

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Brief Report: Biochemical Correlates of Clinical Impairment in High Functioning Autism and Asperger’s Disorder

Cited by 24 publications

References 40 publications

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

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

Variants in several genomic regions associated with asperger disorder

Towards a neurochemical profile of the amygdala using short‐TE ¹H magnetic resonance spectroscopy at 3 T

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Brief Report: Biochemical Correlates of Clinical Impairment in High Functioning Autism and Asperger’s Disorder

Cited by 24 publications

References 40 publications

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

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

Variants in several genomic regions associated with asperger disorder

Towards a neurochemical profile of the amygdala using short‐TE 1H magnetic resonance spectroscopy at 3 T

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

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

Towards a neurochemical profile of the amygdala using short‐TE ¹H magnetic resonance spectroscopy at 3 T