In vivo translocator protein in females with autism spectrum disorder: a pilot study.

Sex-based differences in the prevalence of autism spectrum disorder (ASD) are well-documented, with a male-to-female ratio of approximately 4:1. The clinical presentation of the core symptoms of ASD can also vary between sexes. Previously, positron emission tomography (PET) studies have identified alterations in the in vivo levels of translocator protein (TSPO)-a mitochondrial protein-in primarily or only male adults with ASD, with our group reporting lower TSPO relative to whole brain mean in males with ASD. However, whether in vivo TSPO levels are altered in females with ASD, specifically, is unknown. This is the first pilot study to measure in vivo TSPO in the brain in adult females with ASD using [11C]PBR28 PET-magnetic resonance imaging (MRI). Twelve adult females with ASD and 10 age- and TSPO genotype-matched controls (CON) completed one or two [11C]PBR28 PET-MRI scans. Females with ASD exhibited elevated [11C]PBR28 standardized uptake value ratio (SUVR) in the midcingulate cortex and splenium of the corpus callosum compared to CON. No brain area showed lower [11C]PBR28 SUVR in females with ASD compared to CON. Test-retest over several months showed stable [11C]PBR28 SUVR across time in both groups. Elevated regional [11C]PBR28 SUVR in females with ASD stand in stark contrast to our previous findings of lower regional [11C]PBR28 SUVR in males with ASD. Preliminary evidence of regionally elevated mitochondrial protein TSPO relative to whole brain mean in ASD females may reflect neuroimmuno-metabolic alterations specific to females with ASD.

Tracing the History of the Human Translocator Protein to Recent Neurodegenerative and Psychiatric Imaging.

The human 18 kDa translocator protein (TSPO) has been widely used as a measure of glial activation in health and disease. With the continuous progress of radiotracers with increased affinity and selectivity, associations between TSPO expression, disease severity, and progression have been examined, particularly in neurodegenerative disorders such as multiple sclerosis (MS), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). However, findings in psychiatric disorders have prompted reassessment of the interpretation of regional TSPO expression differences in the brain, specifically with respect to potential neuroinflammatory components. This "mini" Review aims to guide readers through the complexity of TSPO imaging research by identifying the successes, challenges, and promising new directions of the field. We will provide a brief history of how TSPO imaging has evolved over the last three decades and present lessons learned in the context of neurodegenerative and psychiatric disorders.