On the topic of metabolic disturbances in Autism, huge fan of the work Dr. Randy Blakely is doing on the links between Serotonin metabolism and Autism. One of the most surprising, and strongest (25-30% of patients), biomarkers for Autism is actually Platelet Hyperserotonemia (high levels of bound Serotonin in the blood).
For decades it's been without explanation but recently Dr Blakely has described a bunch of cases where it was narrowed down to SERT transporter polymorphisms and inflammation.
I've got a pet hypothesis that differences in Serotonin metabolism (and receptor hypersensitivity) might play a role in why SSRIs aren't generally considered a first line treatment for ASD symptoms, https://www.pnas.org/doi/abs/10.1073/pnas.1112345109
Dr. Blakelys lab has produced knock-in mice with the rare SERT variants described, and they have exhibited the behavioral and biochemical markers of ASD. It's actually a very remarkable finding. They also saw a reduction in ASD symptoms by pharmaceutically blocking the offending inflammatory pathways.
So I think at-least for the tiny fraction of ASD patients with these rare SERT variants there's actually a chance that they are a major driver of the disorder. Regardless it provides a tantalizing look at some of the upstream pathways that could be involved more generally.
I think we're going to find the disorder is very heterogenous and there will be many different subtypes and pathways involved.
For decades it's been without explanation but recently Dr Blakely has described a bunch of cases where it was narrowed down to SERT transporter polymorphisms and inflammation.
Worth a watch for those interested in the weeds of this stuff: https://www.youtube.com/watch?v=cpDtuKV5CJs
I've got a pet hypothesis that differences in Serotonin metabolism (and receptor hypersensitivity) might play a role in why SSRIs aren't generally considered a first line treatment for ASD symptoms, https://www.pnas.org/doi/abs/10.1073/pnas.1112345109