I wrote this quite quickly one morning when I needed to explain a point I was trying to make to a friend. The whole thing really needs to be edited and revisited, which I’ll do when I have time, but I think there are enough valid points for it to be included as a starting point here……
The monoamine serotonin is not, as has been thought since the 1970s, directly involved in the subjective control of mood, hunger, drives and other autonomous functions. Rather, it acts, as its name implies, as a mediator of the fine balance between heart rate, heart beat strength, blood pressure and blood vessel dilation/constriction.
The circulatory system of the human body can be affected in many ways, some of which are systemic, and some of which are localised. It is naïve to think that the entire circulatory system is in a uniform state of constriction or dilation, although some conditions and reactions can have a systemic effect.
The role of serotonin, therefore, is to turn on or turn off various organs and structures within organs (including structures of the brain) and act as a gating system for blood flow and therefore oxygen contained in that blood. It is the oxygen within the blood which signals the activity within a structure.
The very recent concept of cotransmission, in which receptors thought to have affinity for only one of the monoamines have been shown to elicit different responses when another neurotransmitter type is bound to them muddies the water somewhat, although I believe this is merely a mechanism to multiply the staggering number of combinations of activity which make up consciousness and metabolism.
Mental illness, in a broad sense, can be seen as an alteration in consciousness. Many compounds, the majority of which have an effect on serotonin receptors (phenythylamines, tryptamines, antidepressants etc) bring about an alteration in consciousness (a change in mood, hallucinations, altered perception) and physical changes (abnormal temperature regulation, flushing, increased tactile awareness, energy/lethargy etc), although the mechanism by which they cause these changes has never been understood. It was long thought that the release, activation of receptors by and inhibition of reuptake of serotonin resulted in increased brain activity and excitement.
In an experiment in March 2011, scientists, for the first time, administered what is considered a psychedelic tryptamine, psilocybin, to a subject who had been placed in a brain scanner, to monitor the changes in the brain objectively whilst recording subjective changes from the subject. Rather than seeing increased brain activity, which they had expected once the subject began hallucinating, they were amazed to find that some structures within the brain had become less active (as shown by a reduction in blood flow rather than a change in electrical activity). They hypothesised that these structures somehow acted as “filters” for external stimuli.
So…. If it’s possible that reduced, and not increased (in this example) blood flow can result in the shutting down, or gating, of structures which normally give order to the processing of external stimuli, is it possible that the hallucinations present in some cases of mental illness are also caused by an insufficient blood flow to these or similar structures within the brain?
Before I continue with some arguments which I think show that cerebral vascular insufficiency can lead to both psychosis and depression, I’ll look at some of the hypotheses which have been postulated so far for the development of mental illness.
One problem which has dogged the investigations into the causes of mental illness so far has been that any one cause postulated is dismissed when evidence suggests that the pattern is not consistent. For example, a viral route to the mechanism is dismissed, because a large percentage of the subject group do not conform to expected results. Rather, we should look at a range of risk factors, which may be implicit on their own, or in conjunction with other risk factors. Each of the risk factors does not determine on its own whether mental illness will result, but may add to susceptibility given certain conditions.
1 Genetic susceptibility.
Essentially, an inherited abnormality or underdevelopment of the vascular system.
2 Month of birth.
In the northern hemisphere, there have been anecdotal links between winter or spring births and an increase in prevalence of mental illness. Peripheral vasoconstriction is an autonomous response to cold weather. Blood leaves the extremities to reduce heat loss and maintain a core temperature (which is why hands, feet, ears and nose suffer the most in cold weather). Brain development in the unborn foetus mainly takes place in the last trimester of pregnancy, which with winter births in the northern hemisphere coincides with the return of cold weather. Historically, a high infant mortality rate for humans mean that multiple pregnancies and births were common. It is not beyond the realms of the imagination to expect that an autonomous reaction to cold weather during pregnancy would be to protect the “host” rather than the unborn child, to further the chances of procreation in the future. This could mean that blood containing nutrients, hormones and growth factors is diverted to the core of the mother, perhaps resulting in an underdeveloped or abnormal cerebral vascular system in the unborn child.
3 Substance abuse.
Well documented are the effects of amphetamine (on which the dopamine hypothesis of psychosis is based) and cocaine on the vascular system. Each cause vasoconstriction and an increase in blood pressure. Less well known, but documented, is the effect of cannabis on the circulatory system. It too causes cerebral vasoconstriction, albeit via a different mechanism.
Stress and trauma both release norepinephrine into the bloodstream (part of fight or flight syndrome) which serves to constrict the blood vessels and increase blood pressure, along with many other physiological changes.
Often ridiculed is the idea postulated by E Fuller Torrey, the author of Surviving Schizophrenia, that there may be a viral route to the development of Schizophrenia. People laugh it off, “best stay away from cat litter!”, and telling one and all that they either did or didn’t grow up with a cat, and did or didn’t develop schizophrenia. Whatever. Viral or bacterial causes of tissue inflammation are very common, and it’s not difficult to imagine that even slight inflammation of brain tissue, or inflammation of the endothelial cells which line the very narrow blood vessels serving the structures of the brain, some of which are only the diameter of a single blood cell, can have a negative impact on the capacity of the vessel to deliver blood and oxygen efficiently.
The science of the study of vascular health is relatively recent. In fact, it’s a recently as 1999 that the significance of endothelial cells has been discovered. The endothelium lines the blood vessel walls, and is responsible for the elasticity of those vessels. It produces, uses and stores nitric oxide, which is important for relaxing vessels and maintaining a stable blood pressure, and ultimately protecting the heart. Many things can contribute to a healthy or unhealthy endothelium, probably best to google it if you want to know more. Suffice to say, it’s now regarded as the number one preserver of health, far more important than, and related to, the function of the heart.
Imagine if you can, the tiny blood vessels supplying oxygen to the billions of structures within your brain. If they are flexible and healthy, they can adjust to variations in blood volume and pressure – they are elastic, and soon return to their original shape following a period of dilation. Now imagine that one of those blood vessels, only the diameter of one blood cell, has an unhealthy lining, stiff and not elastic. If stretched during a period of stress (via any of the mechanisms described previously), once the stressor has gone, the vessel would just collapse, denying normal blood flow.
If you research the things which contribute to a healthy endothelium, you’ll see a remarkable link with dietary supplements and vitamins which have been anecdotally linked with a reduction in psychiatric symptoms. Fish oil, for example, is essential for endothelial health, as it destroys the saturated fat which can block and plaque blood vessels. L-arginine, which promotes our manufacture of nitric oxide, does a great job of reversing the damage caused to our vessels by environmental factors; note though, that nicotine interferes with the ability to use L-arginine to produce NO.
Until the late 1990s, it was thought that we were born with a limited number of brain cells, and that those cells merely died over time, leading to a decline in cognitive abilities which increased with age. It’s since been shown that neurogenesis is not only possible in humans, but is normal. Plasticity is essential. Much has been written on the subject, so research it at leisure if you so desire.
Antidepressants which work on increasing levels of available serotonin have been around for quite a few years, although their mechanism of action has never been understood. Latest thinking suggests that the only way that these medications work is by facilitating neurogenesis – the creation of new brain cells. The delayed onset of action of the majority of these medications has been shown to exactly parallel the time needed for neurogenesis within structures of the brain. As efficient in relief of symptoms over a similar period of time has been shown to be moderate to vigorous exercise.
I suggest that via a shared mechanism (meds increasing serotonin which “gates” extra blood to facilitate neurogenesis; exercise simply helping the heart to beat faster and harder to force blood through the crippled or unhealthy blood vessels to their “turned off” structural destinations), the increased blood flow is what is important. Not only is it important to improve the health of our blood vessels, it is important to reduce the viscosity of our blood to enable it to flow freely.
Interestingly, blocking dopamine (via antipsychotic drugs) has been shown to inhibit neurogenesis, which may explain why depression is so common in those with psychosis, and also why those people seem to respond poorly to antidepressant medication, which, as mentioned, is thought to exhibit it’s effects by facilitating neurogenesis.
One important weapon in our armoury to reach this state is, I believe, the simple aspirin. Aspirin has many health benefits, other than those I speculate about here, and recently doctors have recommended that everyone can benefit from regular aspirin, and that the tiny risk of side effects is far outweighed by the potential benefits.
I believe that aspirin is beneficial to those with mental illness in two ways – firstly, it thins the blood, facilitating easier flow. Secondly, it is a very effective anti-inflammatory – that is, it reduces swelling, which, in the cases of tiny capillaries may be so small as to be undetectable – and therefore also increase blood flow.
Mental illnesses are complex, and no doubt there can be psychological issues contributing to the myriad of symptoms experienced. I believe that these can be more readily addressed once the basic physiological functions of the brain have been restored to normality.