Bradley S Peterson1, Ariana Zargarian2, Jarod B Peterson3, Suzanne Goh4, Siddhant Sawardekar3, Steven C R Williams5, David J Lythgoe5, Fernando O Zelaya5, Ravi Bansal6. 1. Institute for the Developing Mind, Children's Hospital Los Angeles, Los Angeles, California; Keck School of Medicine, University of Southern California, Los Angeles, California. Electronic address: bpeterson@chla.usc.edu. 2. Keck School of Medicine, University of Southern California, Los Angeles, California. 3. Institute for the Developing Mind, Children's Hospital Los Angeles, Los Angeles, California. 4. Cortica Healthcare, San Diego, California. 5. Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. 6. Institute for the Developing Mind, Children's Hospital Los Angeles, Los Angeles, California; Keck School of Medicine, University of Southern California, Los Angeles, California.
Abstract
BACKGROUND: Our aim was to assess resting cerebral blood flow (rCBF) in children and adults with autism spectrum disorder (ASD). METHODS: We acquired pulsed arterial spin labeling magnetic resonance imaging data in 44 generally high-functioning participants with ASD simplex and 66 typically developing control subjects with comparable mean full-scale IQs. We compared rCBF values voxelwise across diagnostic groups and assessed correlations with symptom scores. We also assessed the moderating influences of participant age, sex, and IQ on our findings and the correlations of rCBF with N-acetylaspartate metabolite levels. RESULTS: We detected significantly higher rCBF values throughout frontal white matter and subcortical gray matter in participants with ASD. rCBF correlated positively with socialization deficits in participants with ASD in regions where hyperperfusion was greatest. rCBF declined with increasing IQ in the typically developing group, a correlation that was absent in participants with ASD, whose rCBF values were elevated across all IQ levels. rCBF in the ASD group correlated inversely with N-acetylaspartate metabolite levels throughout the frontal white matter, with greater rCBF accompanying lower and increasingly abnormal N-acetylaspartate levels relative to those of typically developing control subjects. CONCLUSIONS: These findings taken together suggest the presence of altered metabolism, likely of mitochondrial origin, and dysfunctional maintenance processes that support axonal functioning in ASD. These disturbances in turn likely reduce neural efficiency for cognitive and social functioning and trigger compensatory responses from supporting glial cells, which subsequently increase rCBF to affected white matter. These findings, if confirmed, suggest cellular and molecular targets for novel therapeutics that address axonal pathology and bolster glial compensatory responses in ASD.
BACKGROUND: Our aim was to assess resting cerebral blood flow (rCBF) in children and adults with autism spectrum disorder (ASD). METHODS: We acquired pulsed arterial spin labeling magnetic resonance imaging data in 44 generally high-functioning participants with ASD simplex and 66 typically developing control subjects with comparable mean full-scale IQs. We compared rCBF values voxelwise across diagnostic groups and assessed correlations with symptom scores. We also assessed the moderating influences of participant age, sex, and IQ on our findings and the correlations of rCBF with N-acetylaspartate metabolite levels. RESULTS: We detected significantly higher rCBF values throughout frontal white matter and subcortical gray matter in participants with ASD. rCBF correlated positively with socialization deficits in participants with ASD in regions where hyperperfusion was greatest. rCBF declined with increasing IQ in the typically developing group, a correlation that was absent in participants with ASD, whose rCBF values were elevated across all IQ levels. rCBF in the ASD group correlated inversely with N-acetylaspartate metabolite levels throughout the frontal white matter, with greater rCBF accompanying lower and increasingly abnormal N-acetylaspartate levels relative to those of typically developing control subjects. CONCLUSIONS: These findings taken together suggest the presence of altered metabolism, likely of mitochondrial origin, and dysfunctional maintenance processes that support axonal functioning in ASD. These disturbances in turn likely reduce neural efficiency for cognitive and social functioning and trigger compensatory responses from supporting glial cells, which subsequently increase rCBF to affected white matter. These findings, if confirmed, suggest cellular and molecular targets for novel therapeutics that address axonal pathology and bolster glial compensatory responses in ASD.
Authors: J Kaufman; B Birmaher; D Brent; U Rao; C Flynn; P Moreci; D Williamson; N Ryan Journal: J Am Acad Child Adolesc Psychiatry Date: 1997-07 Impact factor: 8.829
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Authors: Anastasia G Papaioannou; Eva Kalantzi; Christos C Papageorgiou; Kalliopi Korombili; Anastasia Βokou; Artemios Pehlivanidis; Charalabos C Papageorgiou; George Papaioannou Journal: Heliyon Date: 2021-09-21