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

Abstract

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 [¹⁸F]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 ([¹⁸F]FEPPA V_T) in four previously identified regions of interest (ROI): prefrontal, temporal, cerebellar, and anterior cingulate cortices. We observe no significant difference in [¹⁸F]FEPPA V_T relative to controls (F_(1,26)= 1.74, p = 0.20). However, 2 ASD participants with higher V_T 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 [¹⁸F]FEPPA V_T in ASD participants compared to controls (F_(1,24)= 6.62, p = 0.02). This preliminary analysis provides evidence suggesting an atypical neuroimmune state in ASD.

Fig. 1. [¹⁸F]FEPPA V_T in typically developing control (TD, open symbols) and ASD participants (solid symbols) for the prefrontal cortex, temporal cortex, cerebellar cortex, anterior cingulate cortex and whole gray matter.

Groups were classified according to their TSPO rs6971 genotype as high-affinity binders (HABs) or mixed affinity binders (MABs). ASD participants with a concurrent major depressive episode (MDE) were both HABs, and are highlighted with a square symbol (n = 2). The individual data points show the original [¹⁸F]FEPPA V_T values and the horizontal bars indicate group means adjusted for TSPO rs6971 genotype using the estimated marginal means of each region (including ASD participants with a concurrent MDE).