Differential regulation of the mTOR pathway across genetic and environmental animal models of autism spectrum disorder:A meta-analysis

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder of which the etiology is unknown. ASD is thought to result from altered brain development caused by genetic and/or environmental factors. As such, many different factors have been identified and consequently studied in a variety of genetic and environmental animal models. Recently, the mammalian target of rapamycin (mTOR) pathway has been implicated in synaptic remodeling, a process strongly associated with ASD. To investigate whether differentially regulated mTOR signaling is a shared mechanism in this heterogeneous neurodevelopmental disorder, we performed a systematic review and meta-analysis of 156 studies that investigated this pathway in a large variety of genetic and/or environmental animal models for ASD. Using a random-effects model we found that, compared to controls, expression of several mTOR pathway-related proteins was consistently increased or decreased across ASD models. Using subgroup analyses, we further specified the results and found that expression of other mTOR pathway-related proteins varied depending on species, sex, age, or brain region. Our results support involvement of mTOR pathway-related proteins in ASD, but also demonstrate a high degree of variability in mTOR regulation across animal models. These findings contribute to our understanding of common mechanisms in ASD development that will require further investigation.