Brief report: High frequency of biochemical markers for mitochondrial dysfunction in autism: no association with the mitochondrial aspartate/glutamate carrier SLC25A12 gene.
ABSTRACT In the present study we confirm the previously reported high frequency of biochemical markers of mitochondrial dysfunction, namely hyperlactacidemia and increased lactate/pyruvate ratio, in a significant fraction of 210 autistic patients. We further examine the involvement of the mitochondrial aspartate/glutamate carrier gene (SLC25A12) in mitochondrial dysfunction associated with autism. We found no evidence of association of the SLC25A12 gene with lactate and lactate/pyruvate distributions or with autism in 241 nuclear families with one affected individual. We conclude that while mitochondrial dysfunction may be one of the most common medical conditions associated with autism, variation at the SLC25A12 gene does not explain the high frequency of mitochondrial dysfunction markers and is not associated with autism in this sample of autistic patients.
SourceAvailable from: Martha R Herbert
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ABSTRACT: IMPORTANCE Impaired mitochondrial function impacts many biological processes that depend heavily on energy and metabolism and can lead to a wide range of neurodevelopmental disorders, including autism spectrum disorder (ASD). Although evidence that mitochondrial dysfunction is a biological subtype of ASD has grown in recent years, no study, to our knowledge, has demonstrated evidence of mitochondrial dysfunction in brain tissue in vivo in a large, well-defined sample of individuals with ASD. OBJECTIVES To assess brain lactate in individuals with ASD and typically developing controls using high-resolution, multiplanar spectroscopic imaging; to map the distribution of lactate in the brains of individuals with ASD; and to assess correlations of elevated brain lactate with age, autism subtype, and intellectual ability. DESIGN, SETTING, AND PARTICIPANTS Case-control study at Columbia University Medical Center and New York State Psychiatric Institute involving 75 children and adults with ASD and 96 age- and sex-matched, typically developing controls. MAIN OUTCOMES AND MEASURES Lactate doublets (present or absent) on brain magnetic resonance spectroscopic imaging. RESULTS Lactate doublets were present at a significantly higher rate in participants with ASD (13%) than controls (1%) (P = .001). In the ASD group, the presence of lactate doublets correlated significantly with age (P = .004) and was detected more often in adults (20%) than in children (6%), though it did not correlate with sex, ASD subtype, intellectual ability, or the Autism Diagnostic Observation Schedule total score or subscores. In those with ASD, lactate was detected most frequently within the cingulate gyrus but it was also present in the subcortical gray matter nuclei, corpus callosum, superior temporal gyrus, and pre- and postcentral gyri. CONCLUSIONS AND RELEVANCE In vivo brain findings provide evidence for a possible neurobiological subtype of mitochondrial dysfunction in ASD.JAMA Psychiatry 04/2014; 71(6). DOI:10.1001/jamapsychiatry.2014.179 · 12.01 Impact Factor
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ABSTRACT: Autism Spectrum Conditions (ASC) are a group of developmental conditions which affect communication, social interactions and behaviour. Mitochondrial oxidative dysfunction has been suggested as a mechanism of autism based on the results of multiple genetic association and expression studies. SLC25A12 is a gene encoding a calcium-binding carrier protein that localizes to the mitochondria and is involved in the exchange of aspartate for glutamate in the inner membrane of the mitochondria regulating the cytosolic redox state. rs2056202 SNP in this gene has previously been associated with ASC. SNPs rs6716901 and rs3765166 analysed in this study have not been previously explored in association with AS. We genotyped three SNPs (rs2056202, rs3765166, and rs6716901) in SLC25A12 in n = 117 individuals with Asperger syndrome (AS) and n = 426 controls, all of Caucasian ancestry. rs6716901 showed significant association with AS (P = 0.008) after correcting for multiple testing. We did not replicate the previously identified association between rs2056202 and AS in our sample. Similarly, rs3765166 (P = 0.11) showed no significant association with AS. The present study, in combination with previous studies, provides evidence for SLC25A12 as involved in the etiology of AS. Further cellular and molecular studies are required to elucidate the role of this gene in ASC.Molecular Autism 03/2014; 5(1):25. DOI:10.1186/2040-2392-5-25 · 5.49 Impact Factor