New theory about over excitation in highly sensible individuals / ADHD / para-autism.

[Jonneh]

For example:

http://www.ncbi.nlm.nih.gov/pubmed/21158553

http://www.ncbi.nlm.nih.gov/pubmed/20724638

Thanks. Frankly, I was sceptical that an effector like mTOR, which integrates so many intracellular signalling pathways, could form an axis underlying something as complex as depression. That's the big caveat of rodent models of highly nuanced and distinctly human disorders (it is depression we're talking about). I also get uncomfortable when spine growth and LTP are seen as 'good things' and 'memory promoting'. That's not how it works at all.

But fair enough, synaptogenesis is undoubtedly an important effect, whatever it is doing wherever they found it, and that ketamine acts through mTOR to effect this process is interesting, even surprising, since NMDA receptor-dependent synaptic and structural plasticity (like synapto-/spinogenesis) will probably be blocked (although there is controversy about that in the case of LTD).

 

[CFC]

Yeah I don't think they're making any outright claims of causality, and of course it is rodents, but the potential involvement of mTOR is interesting - and maybe not entirely surprising.

http://www.ncbi.nlm.nih.gov/pubmed/24321772

 

[Jonneh]

Re AMPA receptors: nice correlations in that paper, but the only solid mechanistic effects of ketamine we know of are still through its NMDA antagonism. I would sooner believe that effects on mTOR (or BDNF) occur through that mechanism (albeit in a more convoluted manner which may even result in AMPA receptor activation, on downstream neurons, for example) than through direct actions with AMPA receptors. There would be ways to explain it, but ketamine having much of an effect on AMPA receptors doesn't fit with the subjective experience at all.

I certainly wouldn't take its role in helping depression as cut and dried, but point taken: something's going on between ketamine and mTOR! We want to know more!