Another play on words form the title of this post. Whilst no means no (or even NoMeansNo if you are partial to a little punk rock), NO in this case actually refers to nitric oxide and a few snippets of research potentially relevant to autism and a few other conditions.
A recent paper in bipolar disorder research brought me to this post. The paper by Bielau and colleagues* suggested evidence of issues with NO signalling might be a facet of bipolar disorder. When I read the words "influences the balance of monoaminergic and glutamatergic neurotransmission" I thought to myself that it was about time to look at NO with autism in mind, given the quite interesting links being suggested around glutamate and autism for example.
Indeed, it was perhaps inevitable that I would arrive at NO at some point on this blog given the numerous references to inflammation and oxidative stress seemingly present in some cases of autism spectrum conditions as exemplified by the post on glutathione and autism. The more general connection between NO and inflammation is a complicated one but nevertheless an important one. I might add that I will be coming back to inflammation and autism in future posts.
A brief history of NO and autism.
This paper by Zoroglu and colleagues, whilst built on a small participant group, paved the way for several subsequent studies of NO metabolites in plasma and urine. Zoroglu is a name that comes up quite a bit in NO research. Findings of elevated levels of NO metabolites are pretty consistent in the autism studies so far as evidenced by this paper and this paper. Even research which did not find any group connection between elevated NO and autism, implied that the onward problems following a Clostridial infection in a case of autism might show elevated NO values (Clostridia difficile toxins can do some pretty nasty things to the gut).
More recent publications continue the theme. So this paper by Essa and colleagues** added to the melting pot of research. Based on the analysis of a small group of children with autism living in the Sultanate of Oman, a significant elevation among several markers of oxidative stress were found including plasma levels of NO. An even more recent study published by Tostes and colleagues*** also reported elevations in NO alongside quite a few other issues such as elevations in interferon-gamma (IFN-γ) and some other very interesting peptide findings (e.g. VIP). Again based on quite a small participant group.What this might imply is that elevated NO levels in cases of autism may represent cases of autism with some kind of 'inflammatory' process attached.
Not yet convinced about a possible role for NO in some cases of autism?
Even the father of the minicolumn hypothesis Prof. Manuel Casanova might be swayed by the potential for a link. What to do about NO is altogether another matter and indeed it might not just be a case of trying to reduce levels or somehow reduce the source of the inflammation. A positive effect from NO in relation to cardiac function has been pretty well documented as evidence by papers such as this one. NO might also happen to be quite a good antioxidant; with a little seemingly going a long way.
The question is whether there might be a tipping point; a point where too much of a good thing causes problems and whether what has been seen in cases of autism and in other conditions, represents too much?
* Bielau H. et al. Immunohistochemical evidence for impaired nitric oxide signaling of the locus coeruleus in bipolar disorder. Brain Research. 2012; 1459: 91-99
** Essa MM. et al. Increased markers of oxidative stress in autistic children of the Sultanate of Oman. Biological Trace Element Research. November 2011.
*** Tostes MH. et al. Altered neurotrophin, neuropeptide, cytokines and nitric oxide levels in autism. Pharmacopsychiatry. March 2012.