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.