JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
RESEARCH SUPPORT, NON-U.S. GOV'T
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Mitochondrial dysfunction as a neurobiological subtype of autism spectrum disorder: evidence from brain imaging.

JAMA Psychiatry 2014 June
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.

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