In the mouse model of Rett, the symptoms are very well recapitulated, and there is virtually complete rescue following re-expression of MeCP2. The symptoms that are resolved can’t be due to structural changes, or they wouldn’t resolve.

I think that psychosis and autism are the two extremes of a spectrum, but that spectrum is set in utero. My hypothesis is that low NO in utero causes brain development skewed in an autism direction, high NO (as in maternal infections an iNOS expression) cause skewing in a psychosis direction.

This in utero exposure only determines the neuroanatomy and the epigenetic programming of the brain. Low NO in utero causes development along a low NO phenotype trajectory.

I think that a psychotic break occurs later in life due to acute low NO which causes low functional connectivity. This can be induced artificially (i.e. by stimulants of abuse), by stress, or acute trauma.

Sorry to leave such a short and disjointed comment. This area is very interesting to me and I am coming at it solely through the NO connection which explains a great deal of it. My access to blogger.com is now limited so I can’t read or respond to blogs such as this as I would like, or be on facebook.

The low NO induced neuroanatomy is protective against low NO later in life. The finer scale connectivity allows for greater resistance to reduced NO causing decreased functional connectivity. People with ASDs may have a melt-down, but they do not become psychotic. People without the higher minicolumn density become psychotic.

Social isolation causes decreased number of NOS expressing neurons.

http://www.ncbi.nlm.nih.gov/pubmed/10938444

I think this is the source of the “autism-like” behaviors of Harlow’s socially isolated monkeys. Some isolated monkeys exhibit superior cognitive capacities, i.e. savant abilities.

http://www.ncbi.nlm.nih.gov/pubmed/1936581

I think the data fits a two-hit hypothesis, where the neuroanatomy which develops in utero and experiencing low NO later in life are both important.

I see bipolar as cycling between high and low NO. The manic or hypomanic phase is very low NO, a depressed phase is merely low NO.

Autism is a very poor publicly understood phenomenon and any child developmentally delayed or having difficulties is automatically labeled autistic. One can only hope for more eduction and better endophenotypes, so that the diagnosis is far more accurate. If the child has learning difficulties but shows heightened activities in other psychosis associated phenomenon like pretend play etc, we can definitely rule out autism, so yes the concept of autism and psychosis as opposing phenomenon can lead to better diagnosis.