New Targets for Anti-Depressants?

This post is very long (3850 words) and very difficult. It is a preliminary investigation of the idea that depression arises from chronic sustained arousal leading to amine depletion and various other physiological changes.

This news release from Science Daily highlights a new pharmacological approach to treating depression. The nutshell is this: there is a class of proteins in our brains called RGS proteins which inhibit the signalling of various neurotransmitters. By manipulating the RGS protein that inhibits serotonin signalling we can treat depression. Most current anti-depressant drugs attempt to increase the levels of serotonin or norepinephrine. Unfortunately there are now some studies emerging which indicate these current anti-depressants can increase the risk to develop a range of disorders, from kidney problems to cataracts. Generally the risk profiles are low but given the very widespread use of anti-depressants it could constitute a considerable public health cost. Which raises an interesting question: if we place our faith in these statistical analyses then is the government entitled to extract an "pharmaceutical externality tax" to address the health risks and subsequent costs associated with drug side effectss? Yeah, like that'll ever happen. We'll develop a new class of anti-depressants, and wait 30 years before we know about the associated risks ... .



My unalloyed cynicism aside, what caught my interest about this research is the reference to RGS proteins. It reminded me I read in 1999:

Article: 

Upregulation of RGS7 may contribute to tumor necrosis factor-induced changes in central nervous function

Journal: NATURE MEDICINE • VOLUME 5 • NUMBER 8 • AUGUST 1999

Immune Driven Psychopathology in Mice?

It all began way back in the 19th century. "Sickness Behavior" was observed in humans and farm animals. As that Wiki article goes on to explain, there are some interesting similarities between sickness behavior and depression. This has been an active area of research for many years now. One key article is this one from 2003. This strange and puzzling linkage between the nervous systems and immune systems has been evidenced by the following:

• Shizophrenia is associated with differing rates of cancer and autoimmune disease from others.
• Epileptics also have altered immunological responses, this possibly driven by hippocampal - fornix - PVN networks(guess).
• Traumatic brain injury can induce a variety of physiological changes, from altered melatonin production to variations in circadian cortisol secretion. 

This is going to be difficult ...

Why Doesn't the Immune System Target Tumours?

Recently some people told me about how an Italian cardiologist is making a big fuss out of the fact that when he removes a tumour he finds fungal infections around it, the implication being the fungal infection is causing the tumour. Classic case of mis-attribution of cause. Despite the claims of the news article and\or researchers, this is not news. By way of example, look at the following graphic which is drawn from this research piece.

The article was published in November 2007. Yes, scientists love to claim they were the first to make the discovery! If you scroll down the link above you can download a powerpoint presentation pertaining to this issue. To gain some insight into why this finding is so important, read on.

Complexity in Biology: an Epistemological Nightmare

Given the massive amount of research in biomedicine it is tempting to think that we are now in the process of completing the picture of biological processes and just need to keep on moving forward. I wish, a more sober conclusion is that ongoing research into the particulars of biological processes and is going to leave us further bewildered. Fortunately there are some researchers who are strenuously attempting to create models of biological processes This particular approach offers considerable hope because it suggests that we do not need to understand in detail all the relevant processes in a biological function. You can read the Science Daily News item here. The authors even go so far as to state:

 In particular, these findings suggest not only that one may not be able to understand individual elementary reactions from macroscopic observations, but also that such an understanding may be unnecessary.

For myself at least this is very promising because I have long held the view that while the research into the individual elements involved in biological processes is very important a more useful understanding will never arrive simply through more "butterfly collecting" but through the development of models that do not require a taking into account of all these individual agents. To understand why I have long held this view please read on.

Cancer and Cellular Connections

Days of strange co-incidences. Today a friend in the USA sent me a fascinating little article from the Howard Hughes Medical Institute. Basically the story goes like this:

Cancer cells have very strong "pulling power", they tightly bind together. This has serious therapeutic implications which be latter addressed. What struck me as so odd about this research was just yesterday I read how immune cells also rely on pulling power to ensnare and devour dangerous cells.

History of Madness - Michel Foucault

History of Madness

Michel Foucault

Routledge

2006

At the start of this text is a recommendation by R. D. Laing, a founder of the anti-psychiatry school. Laing states:

"... brilliantly written, intellectually rigourous, and with a thesis that thoroughly shelves the assumptions of traditional psychiatry."

As I will later illustrate, Mr. Laing is being somewhat exuberant in his praise. Talking of exuberance, the introduction carries this quote from Georges Dumézil: "Foucault's intelligence literally knows no bounds."

Eat Watermelon and save your heart

Watermelon is good for the heart? Yes, and it is also is being touted by some as a "natural viagra". These two issues are inter-related and will be addressed later in the post. This post was prompted by a news item on the BBC website which found that low fat, low carb, and mediterranean diets can reduce the size of plaques in our arteries. The effect was small, only a 5% volume reduction and probably of little value to those with serious coronary plague, at least in the short term. Keep in mind that over the long term that ongoing 5% reduction, if sustained over many years, could be critical in preventing a heart attack.

Have a look at the image on the left. It shows how plague can build up to such high levels it can block the artery and induce occlusive strokes or a heart attack. The typical advice we receive is that we must be carefully control our diet, exercise regularly, and eat heart healthy foods. What is not often mentioned directly relates to benefits of watermelon and other foods that provide a substrate which is essential to maintaining cardiovascular health.

Air Power by Stephen Budiansky

Air Power: From Kitty Hawk to Gulf War 11: A History of the People, Ideas and Machines that Transformed War in the Century of Flight

Stephen Budiansky

Viking, an imprint of Penquin Books

2003



This is a comprehensive text that deals with Air Power in a very informative and entertaining way. The author has been thorough in his research and the text has extensive footnotes and a large bibliography. Despite the author moving into some very technical areas he keeps the reader entertained with a lucid writing style and that is well paced and ideally suited to the subject matter.

One of the more striking themes of the book is how Budiansky looks at what was expected of air power and how often those expectations failed. The mass civilian bombings were expected to quickly bring Germany to its knees, to completely demoralise the populace in the face of such overwhelming destruction of their cities and homes. Never happened. Time and again military planners over estimated the capacity of air power to make decisive blows against the enemy.

That is not to say that air power has been largely ineffectual but rather that air power, while vital in war since WW2, is not a decisive factor in winning war. As an old friend of mine who was in the army used to say: you can't win a war from the air.

Inflammation and Alzheimers

For a long time it was believed that inflammation played a critical role in the development of Alzheimer's. This can be true but needs to be carefully qualified because as the below abstract demonstrates "massive gliosis" induced by interleukin 6 actually prevented amyloid deposition. Look at the gliosis link for the wikipedia entry, it is a good example of when not to trust Wiki. Wiki is very useful for a quick overview of relatively mundane and simple concepts but can be very misleading when dealing with cutting edge research. In the abstract overleaf the bods found that inducing gliosis, which is typically associated with inflammation, is actually leading to clearance of amyloid. Clearance of amyloid is the great interest in current Alzheimer's research and this for the simple reason that amyloid aggregation appears to be a key driving factor in Alzheimer's disease. As usual, with more research, what once looked obvious becomes blurred. Inflammation is found in many pathologies but it is a mistake to assume that inflammation is the cause of that pathology. As this study indicates it can play a vital protective role.

Relative Risk and the Chernobyl Incident

Have a look at the abstract further down. It highlights something that we tend to ignore. We think that something like Chernobyl should have massive consequences but as indicated in studies on Nagasaki and Hiroshima mortality from radiation exposure was surprisingly low; excepting of course those in the immediate blast experience. What this study does highlight though is that even obesity and passive smoking is up there with radiation in terms of public health risk. I have long had concerns about the continuing polluting of our environment and the increasing amounts of artificial chemicals we are exposed too. These risks are "silent risks" in that they receive little attention but collectively these risks are going to cost individuals and governments a great deal of money.