Mitochondrial dysfunction as a neurobiological subtype of autism spectrum disorder: evidence from brain imaging.
Level 4 - case-series / case-control
Case-control study comparing brain MRSI findings between clinical cases and matched controls
PubMed 24718932 · doi:10.1001/jamapsychiatry.2014.179
What was done
Case-control study at Columbia University Medical Center and New York State Psychiatric Institute involving 75 children and adults with autism spectrum disorder (ASD) and 96 age- and sex-matched typically developing controls. High-resolution multiplanar magnetic resonance spectroscopic imaging (MRSI) was used to assess the presence of lactate doublets, map their anatomical distribution, and analyze correlations with age, ASD subtype, intellectual ability, and Autism Diagnostic Observation Schedule (ADOS) scores.
What was found
Lactate doublets were present in 13% of ASD participants compared to 1% of controls (P = .001). Within ASD participants, lactate doublets were detected in 20% of adults versus 6% of children, correlating significantly with age (P = .004). Lactate presence did not correlate with sex, ASD subtype, intellectual ability, or ADOS total or subscores. In ASD cases with detectable lactate, it localized most frequently in the cingulate gyrus, as well as subcortical gray matter nuclei, corpus callosum, superior temporal gyrus, and pre- and postcentral gyri.
Why it matters
Provides direct in vivo neuroimaging evidence of altered brain metabolism in a subset of individuals with ASD, supporting the hypothesis that mitochondrial dysfunction characterizes a distinct neurobiological subtype.
Limits
Cross-sectional case-control design prevents determining causal direction or longitudinal trajectory. Elevated lactate was present in only a minority (13%) of ASD individuals. Spectroscopic imaging measured presence or absence of doublets rather than continuous quantitative lactate concentrations, and direct cellular mitochondrial function was not measured.
Cited by
- context Dr. Suzanne Goh's work identified autism spectrum disorder as involving a mitochondrial energy deficit and demonstrated clinical improvements using mitochondrial therapies.