Choroid plexus alterations in autism spectrum disorder: A PET-MRI study

The choroid plexus (CP), primarily known as the production site of cerebrospinal fluid (CSF), constitutes one of the sites of the blood-CSF barrier and plays a unique role in inflammation propagation, serving as a key regulator of immune responses. Recent work has shown CP enlargement in neurological and psychiatric disorders with immune involvement. To investigate potential neuroimmune and structural alterations in vivo in autism spectrum disorder (ASD), we assessed the CP-localized expression of mitochondrial translocator protein (TSPO) and CP volume in autistic adults. Sixty-five participants, which included 36 autistic participants and 29 non-autistic controls (CON), completed a simultaneous positron emission tomography-magnetic resonance imaging (PET-MRI) scan with the TSPO radiotracer [¹¹C]PBR28. The CP was segmented using subject-level anatomical scans. We observed CP volume enlargement in ASD (mean group difference: 677.8, 95 % CI [331.0, 1025.0], p = 0.0002). In particular, the CP volume of ∼30 % of autistic adults was more than 2 standard deviations above the average CP volume of CON. Exploratory analysis considering sex showed that CP volume was associated with more severe ASD symptoms in autistic males (estimated beta: 153.10, 95 % CI [50.03, 256.30], p = 0.005) and that TSPO in the CP was elevated in autistic females (mean group difference 0.12, 95 % CI [0.03, 0.21], p = 0.01). Our findings reveal volumetric alterations of the human CP in ASD, providing novel insights into the involvement of the CP in ASD.