[11C]PBR28 MR–PET imaging reveals lower regional brain expression of translocator protein (TSPO) in young adult males with autism spectrum disorder
Molecular Psychiatry (2021) 26:1659–1669 https://doi.org/10.1038/s41380-020-0682-z Received: 21 June 2019 / Revised: 12 January 2020 / Accepted: 6 February 2020 / Published online: 19 February 2020
N. R. Zürcher 1,2 ●M. L. Loggia1,2 ●J. E. Mullett3●C. Tseng 1,2 ●A. Bhanot1●L. Richey1●B. G. Hightower1●C. Wu1● A. J. Parmar1●R. I. Butterfield1●J. M. Dubois1,2 ●D. B. Chonde1,2 ●D. Izquierdo-Garcia1,2 ●H. Y. Wey1,2 ●C. Catana1,2 ● N. Hadjikhani 1,2,4 ●C. J. McDougle2,3 ●J. M. Hooker1,2
N. R. Zürcher, zurcher@nmr.mgh.harvard.edu
J. M. Hooker jhooker@mgh.harvard.edu
1Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA
2Harvard Medical School, Boston, MA, USA
3Lurie Center for Autism, Massachusetts General Hospital, Lexington, MA, USA
4Gillberg Neuropsychiatry Center, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden
Abstract
Mechanisms of neuroimmune and mitochondrial dysfunction have been repeatedly implicated in autism spectrum disorder (ASD). To examine these mechanisms in ASD individuals, we measured the in vivo expression of the 18 kDa translocator protein (TSPO), an activated glial marker expressed on mitochondrial membranes. Participants underwent scanning on a simultaneous magnetic resonance–positron emission tomography (MR–PET) scanner with the second-generation TSPO radiotracer [11C]PBR28. By comparing TSPO in 15 young adult males with ASD with 18 age- and sex-matched controls, we showed that individuals with ASD exhibited lower regional TSPO expression in several brain regions, including the bilateral insular cortex, bilateral precuneus/posterior cingulate cortex, and bilateral temporal, angular, and supramarginal gyri, which have previously been implicated in autism in functional MR imaging studies. No brain region exhibited higher regional TSPO expression in the ASD group compared with the control group. A subset of participants underwent a second MR–PET scan after a median interscan interval of 3.6 months, and we determined that TSPO expression over this period of time was stable and replicable. Furthermore, voxelwise analysis confirmed lower regional TSPO expression in ASD at this later time point. Lower TSPO expression in ASD could reflect abnormalities in neuroimmune processes or mitochondrial dysfunction.
Press Release from Harvard Magazine:
“Inflammation link for autism
A neuroimaging study has shown that the brains of young men with autism spectrum disorder have low levels of translocator protein, a substance that appears to play a role in inflammation and metabolism.
This discovery by a team of HMS researchers at Massachusetts General Hospital provides an important insight into the possible origins of autism spectrum disorder.
This developmental disorder, which affects one in fifty-nine children in the United States, emerges in early childhood and is characterized by difficulty communicating and interacting with others. Although the cause is unknown, growing evidence has linked it to neuroinflammation.
One sign of neuroinflammation is elevated levels of translocator protein, which can be measured in the brain using positron-emission tomography and anatomic magnetic resonance imaging.
The research team used these imaging tools to scan the brains of fifteen young adult males with the disorder. The group included both high- and low-functioning participants with varying degrees of intellectual ability. As a control, the team scanned the brains of eighteen non-autistic young men of similar age.
The scans showed that the brains of the young men with the disorder had lower levels of the protein, compared with the brains of non-autistic participants. In fact, those participants with the most severe symptoms of the disorder tended to have the lowest expression of the protein.
The brain regions found to have low expression of the protein have previously been linked to autism spectrum disorder and are thought to govern social and cognitive capacities such as processing emotions, interpreting facial expressions, and empathy.
The researchers point out that the translocator protein has multiple complex roles, some of which promote brain health. Adequate levels of the protein are, for example, necessary for normal functioning of mitochondria. Earlier research has linked malfunctioning mitochondria in brain cells to autism spectrum disorder.
Zürcher NR et al., Molecular Psychiatry, February 2020
