Monday, January 9, 2017

Serotonin - Part 2

As I continue down the pyridoxine-tryptophan-serotonin rabbit hole, I am finding that there is a lot of prior research in this area, in regards to not only epilepsy, but also depression, autism, and a host of other neurological manifestations. There are countless articles that reiterate the connection between pyridoxine and serotonin.

One of the first articles I came across had to do with the kynurenine pathway (KP). By simulating a sort of mock-pyridoxine deficiency, this study successfully showed that tryptophan metabolism occurs almost exclusively through the KP and that a significant decrease in pyridoxine in the brain (among other areas), created an increased dumping of metabolites, including kynurenric acid, which has known anticonvulsant properties. A simple explanation would be that a pyridoxine deficiency leads to an increased susceptibility to seizures in people that have an issue somewhere along this pathway. Does pyridoxine deficiency ultimately lead to a decrease in tryptophan metabolism, which leads to a decrease in serotonin levels? Much of the research that exists indicates yes. Does this reduction in available serotonin lead to some epileptic syndromes? Again, some of the research that exists indicates yes as well. Children with Infantile Spasms (IS) have been shown to have low serotonin levels. Trying to understand exactly how, why, and where this breakdown along the pathway occurs, is the question that keeps being asked.

There was another interesting abstract I found, having to do with the Ketogenic Diet (KD), which is a century old rigorous diet used to treat children with refractory epilepsy, and its relevance to serotonin levels, before and after initiating the diet. The abstract, which can be read here, says this:

'Our study indicates that the KD significantly alters the levels of metabolites of dopamine and serotonin but with a stable ratio HVA/5-HIAA in the CSF of children with refractory epilepsy, which finding may be of importance for the mechanism of action.'

So, there is a legitimate connection between the epilepsy, autism, and depression (read this article) all of which point to a dysfunction of the kynurenine pathway. Investigating this pathway led to me obscure syndromes that I had never heard of, including hydroxykynurinuria. I am certainly not saying that this is particularly relevant to Mira (as the basis around the diagnosis involved a homozygous mutation of the KYNU gene), yet the dysfunction of the kynurenine pathway is interesting. However, in reading the health conditions related to this syndrome, many of them are very relevant.

In looking into just the subject of epilepsy and serotonin levels, there just seems to be a massive amount of literature on the KP and how it ultimately impacts serotonin and other neurotransmitters in the body - it is difficult to get my arms fully around it. If you are interested in reading more on any of this, you can simply do a search through Google Scholar for 'kynurenine pathway dysfunction and epilepsy' and your will get over 2,500 hits. For now, in trying to bring some closure to my last few posts on serotonin, I would recommend reading this article, scrolling down especially to the section entitled 'Brain 5-HT Concentration and Epilepsy'. The downloadable PDF can be found here. It is a good overview of all of the studies in the last 20+ years in regards to serotonin and epilepsy, with endless references at the end to make your head spin.

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