This is from a blog I found written by a guy with Aspberger's who has been doing extensive personal investigation on the role of Nitric Oxide in Autism spectrum disorders. Its a pretty long read, but towards the end, he mentions CFS in his hypothesis in a way that ties in a "dauer" hypothesis and a lot of other concepts. Now, its focused mostly on the role of NO, and so I dont think its the "whole picture", but its a pretty cool written piece that i9s helping me understand some details I was unaware of before. http://daedalus2u.blogspot.com/2008/06/mechanism-for-mitochondria-failure.html In particular, check out this excerpt "Regressive autism and chronic fatigue syndrome I think high NO induced switching of physiology (the low NO ratchet) is one of the fundamental causes of regressive autism, and also of low basal NO in adults as characterized in chronic fatigue syndrome (CFS). Many people with CFS can identify when they acquired it, and it corresponded with an acute serious infection other causes include trauma of surgery or accidents. Similarly, many parents anecdotally identify the immune reaction of a vaccination as a precipitating event leading to regression. However the large scale epidemiology shows no change in incidence of autism with changes in vaccination. My hypothesis is that in susceptible individuals, any immune system activation is sufficient to activate the "low NO ratchet", a vaccination, or one of the zillions of infections of childhood. It is the low NO ratchet that (I hypothesize) causes Gulf War Syndrome. Receiving multiple immune system activations (vaccinations) during a high stress period (being deployed to a war zone) causes basal NO to ratchet lower with each immune system activation until it saturates and produces chronic fatigue. This takes a few weeks, while the mitochondria turn-over and are not replaced (due to the low NO level from the chronic stress). Once mitochondria numbers are low, the low NO state is perpetuated due to superoxide from too few mitochondria being pushed to higher potentials to supply the same ATP. With continually low NO, mitochondria biogenesis can't occur enough to get back to the level that is "normal". Simple oxidative stress alone can cause low NO, and if that low NO persists for long enough, then chronic fatigue will be induced by insufficient replacement of mitochondria. Mitochondria depletion need not be so severe as to cause neuropathy for "regression" or chronic fatigue to occur. All that is necessary is for mitochondria depletion to exceed a threshold such that they achieve a new operating point with fewer mitochondria working at a higher potential. The higher potential generates more superoxide which lowers NO levels and if not enough mitochondria biogenesis occurs, that state can be perpetuated. Only rarely is regressive autism or even any type of autism characterized by neuropathy as in the case of Hannah Poling. I think it is more appropriate to call such cases "neuropathy with autism-like symptoms". Normal "autism" is not characterized by neuropathy. Sufficient neuropathy will cause symptoms of the lack of communication. Lack of communication is also exhibited by some people with autism. Neuropathy is neuronal damage. Autism can occur with zero neuronal damage. I consider it fundamentally wrong to call any disorder characterized by neuropathy "autism". People with autism can experience neuropathy unrelated to their autism and again that is fundamentally wrong to connect that neuropathy to autism. Whether mitochondria depletion progresses to neuropathy depends on how severe the mitochondria depletion is. Perfectly healthy and normal mitochondria can be turned off by this mechanism, which can result in failure of any organ where too many mitochondria are turned off, or in death, or anything in between. The critical factors are how much ATP mitochondria are called on to produce during the high NO state of sepsis (and so how much superoxide they produce), and how high the NO is level during that time."