Psychiatry Below the Neck
There is more and more evidence that schizophrenia and bipolar disorder and perhaps also major depressive disorder, are illnesses affecting the whole body and not just the brain and mind.
It has been known for over a century that some physical problems, including type 2 diabetes mellitus, obesity, cardiovascular diseases and some forms of cancer appear to be more common in people with major mental illnesses. All of this was known long before the current concerns about obesity, diabetes and some antipsychotic medicines. It is also clear that the physical problems cannot just be explained away by social deprivation and poor lifestyle choices.
The new understanding of mental illness as a systemic problem, opens up some extraordinary opportunities for treatment and perhaps even for prevention. In some new research due to be published next month, investigators have identified some abnormal proteins in the liver and on red blood cells that are similar to some abnormal proteins already identified in the brain.
These proteins are primarily involved in energy metabolism in cells and in protection against oxidative stress. The implication from this is that schizophrenia and many of the associated health problems may be a consequence of impaired energy metabolism together with damage by free radicals.
You will see why this is so exciting: it looks as if we have an entirely new way of approaching, treating and perhaps preventing the most serious of mental illnesses.
Dr. Richard G. Petty, MD is a world-renowned authority on the brain, and his revolutionary work on human energy systems has been acclaimed around the globe.
He is also an accredited specialist in internal and metabolic medicine, endocrinology, psychiatry, acupuncture and homeopathy. He has been an innovator and leader of the human potential movement for over thirty years and is also an active researcher, teacher, writer, professional speaker and broadcaster. He is the author of five books, including the groundbreaking and best selling CD series Healing, Meaning and Purpose. He has taught in over 45 countries and 48 states in the last ten years, but spends as much time as possible on his horse farm in Georgia.
If one was to look at the relationship of Bipolar Disorder to its frequent comorbidites, perhaps cl- transport would be the best place to start. IMHO persistent up regulation of NKCC1 would depolarize GABA responses and at the same time effect Mucus transport, pain signalling etc.. Also interesting is the possible connection to the post you made about accutane and depression. Trkb is up-regulated by retinoic acid, which in-turn controls NKCC1 and KCC2.
Cheers,
Glen
Dear Glen,
Chloride transport is indeed one of the candidates. Others are the serotonin transporter (I wrote a short piece about that here: http://richardgpettymd.blogs.com/my_weblog/2006/08/irritable_bowel.html) and yet another moves away form receptors to the cell membrane itself. There is some evidence for disturbed phospholipase A2 activity. There are a few references here: http://psychiatricresourceforum.blogs.com/my_weblog/2006/07/are_schizophren.html
I like your line of reasoning. I know several world class psychopharmacolgists who have been thinking along similar lines. Most are out of town for the next couple of weeks, but I am going to shoot off a few email and see where their work has gone over the last few months since we last talked.
If they have any new material in the public domain I shall post it.
Kind regards,
RP
Hello Dr. Petty,
In my brevity I perhaps gave a wrong impression. I did not mean to imply that Cl- transport is solely responsible for BD. While certainly possible, I posit that any of the suspected or implicated genetic (or environmental) factors will lead to and up-regulation of NKCC1 and corresponding down regulation of KCC2. With so many links in the chain of neural plasticity, the disruption of any one of them (BDNF, NGF, serotonin, mitochondrial function, etc.) will lead to an eventual up/down regulation of NKCC1/KCC2. And seeing that NKCC1 is also expressed outside of the brain also (unlike KCC2) the implications of such should manifest themselves throughout the body. Another example of where this relationship to Cl- may be a factor is in Fibromagilia and Neuropathic pain. Links;
http://www.jneurosci.org/cgi/content/full/25/42/9613
http://www2.neuroscience.umn.edu/eanwebsite/PDF%20GJClub/Nature%20438%201017%202005.pdf
Dear Glen,
Thank you very much for clarifying your point.
I could see your reasoning, but for people less familar wih the field, I think that it was extremely useful for you to flesh out your ideas in more detail.
Thank you also for adding the links.
Kind regards,
RP
Hello again Dr. Petty,
First off I love the blog!
I recent paper by Dr.De Koninck is perhaps the best summation of the issue. The only omission/oversight I could see in it is the oft reported BDNF triggered rise in cl- via trkb, is the mentioned without note to the possibility of the cl- rise being based on activity. Dr. Claudio Rivera has (IMO) done the best work in this regard, showing that activity leads to a down-regulation of KCC2 (also via trkb).
Links.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17182282&query_hl=2&itool=pubmed_docsum
http://www.jneurosci.org/cgi/content/full/24/19/4683
Dear Glen,
Thank you for the kind comment about the blog, and also for the link.
I had not seen the De Koninck paper, and I am asking one of our researchers to get me a copy of the whole paper.
Kind regards,
RP