In vivo imaging translocator protein (TSPO) in autism spectrum disorder

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 47; no. 7; pp. 1421 - 1427
• Main Authors: Simpson, Dominic, Gharehgazlou, Avideh, Da Silva, Tania, Labrie-Cleary, Charlotte, Wilson, Alan A, Meyer, Jeffrey H, Mizrahi, Romina, Rusjan, Pablo M
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-06-2022; Springer International Publishing
• Subjects: Adult; Anilides - metabolism; Astrocytes; Autism; Autism Spectrum Disorder - diagnostic imaging; Autism Spectrum Disorder - metabolism; Brain - diagnostic imaging; Brain - metabolism; Cerebellum; Depressive Disorder, Major - metabolism; Female; Humans; Immune system; Intelligence; Male; Mental disorders; Microglia; Positron emission tomography; Pyridines; Receptors, GABA - genetics; Receptors, GABA - metabolism; Young Adult
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/s41386-022-01306-4

Converging evidence points to the significant involvement of the immune system in autism spectrum disorders (ASD). Positron emission tomography (PET) can quantify translocator protein 18 kDa (TSPO), a marker with increased expression mainly in microglia and, to some extent astroglia during neuropsychiatric diseases with inflammation. This preliminary analysis explored, for the first time, whether TSPO binding was altered in male and female participants with ASD in vivo using full kinetic quantification. Thirteen individuals with ASD (IQ > 70 [n = 12], IQ = 62 [n = 1]), 5 F, 25 ± 5 years) were scanned with [
F]FEPPA PET. Data from 13 typically developing control participants with matching age and TSPO rs6971 polymorphism (9 F, age 24 ± 5 years) were chosen from previous studies for comparison. The two tissue compartment model (2TCM) was used to determine the total volume of distribution ([
F]FEPPA V
) in four previously identified regions of interest (ROI): prefrontal, temporal, cerebellar, and anterior cingulate cortices. We observe no significant difference in [
F]FEPPA V
relative to controls (F
= 1.74, p = 0.20). However, 2 ASD participants with higher V
had concurrent major depressive episodes (MDE), which has been consistently reported during MDE. After excluding those 2 ASD participants, in a post-hoc analysis, our results show lower [
F]FEPPA V
in ASD participants compared to controls (F
= 6.62, p = 0.02). This preliminary analysis provides evidence suggesting an atypical neuroimmune state in ASD.