Day One: Introduction to the Neuroscience and Medicine of Stress

Welcome to Business Intelegant’s five day open course on stress, moods, the brain, and the neuroscience behind it all. There also plenty of sites on stress, aren’t there? But not that many that really get into the meaning of it all in well, a deeper way.

What will help us to understand the neurobiology - and what is going on? What’s happening to our physical bodies? How and why does it alter our mental state? What does it do at a, literally, fundamental level to our cognitive abilities? How do those various hormones, neurotransmitters, and proteins react, and what are they anyway? How can our understanding change?

So, let’s go instead deep into the human brain and suggesting some tools that will define stress more clearly, and show how understanding the physiology of stress makes a difference.

Before we get there we’ll need to look at an aspect of the history of medicine in the first half of the twentieth century.

Or rather one man.

Hans Selye (1907 - 1982)
Hungarian-Canadian Endocrinologist

Hans Selye was born in Hungary in 1907. He may be considered the first to understand, evaluate, and promote the meaning of stress. He even coined the term stress, much like the founder of organization development, Kurt Lewin, (see Business Intelegant’s iGuru guide) coined the word feedback in 1930s from the fact that output feedback to input allowing for self-correction in electrical circuits, from engineering. Obviously engineers use the word stress. Measured in Pascals, in continuum physics all matter is subject to forces (Gas, liquid, plasma, solid) and so stress. In tensile physics, it has come to mean how much pressure a body can withstand before it breaks. And we all get that analogy.

Claude Bernard (1813 - 1878)
The Father Of Modern Physiology

More correctly Selye borrowed from homeostasis as developed by the father of modern physiology Claude Bernard in his famous statement “La fixité du milieu intérieur est la condition d’une vie libre et indépendante.” (A stabile internal environment is the condition for a free and independent life). Homeostasis is more than just how the body controls its temperature, it is how a system, open or closed, regulates its internal environment. And your body is an open system. Food in - Non-food out for starters.

Walter Bradford Cannon (1875 - 1945)

Walter Bradford Cannon, another major influence on Selye, invented the term, homeostasis, in 1932, in his book The Wisdom of the Body. There is a wonderful page on Walter here.

Selye had begun, as early as his second year in medical school to wonder about forces on bodies, internal and external. It is important to note that he never considered stress to be en emotive word, it was simply an indicator that something was happening, good or bad. For example, simply flexing a muscle is stress, as is a feeling of anxiety. Both exert forces.

Selye experimented on mice with various toxins and noticed that even though they developed different diseases they seemed to share some fundamental symptoms, which we will come to in a moment. These are the symptoms of stress, or the General Adaptive Syndrome.

Selye went on to notice the same held good for humans: many different diseases, but the same symptoms boxes were consistently there along with those symptoms peculiar to that specific disorder. He died in 1982, having set up with Alvin Toffler (See Business Intelegant’s iGuru Guide for more details) and Richard Earle, the Canadian Institute of Stress.

For an outstanding personal reminiscence of Hans Seyle look no further than fellow Hungarian Dr Istvan Berczi’s wonderful accounts of his experiences. Just wish all webpages were so good at recording personal history.

OK. So far, so good.

So, what are the symptoms we’re talking about?

Well, Selye describes these, based on observation. He noted that before any major disease was fully apparent patients

“felt and looked ill, had a coated tongue, complained of more or less diffuse aches and pains in the joints, and of intestinal disturbances with loss of appetite.” They also generally “had fever, enlarged spleen or liver, inflamed tonsils, a skin rash.”

So, what are these symptoms caused by? That’s the right question. We have a set of observable symptoms, all common, across the sample population (Our observed patients), who then all go on to develop different conditions.

So, our first conclusion, is that it’s something that’s happening internally.

Generally, but not always, as a result of external stresses.

How do we know that?

Because some sick people with the same diseases seemed to not develop these symptoms, and the observation was that they seemed far more at ease. But we’re jumping some 10 years ahead of ourselves.

His initial observation was that their homeostasis was better. They were, literally, more in control.

Ironically, he was only a second year medical student and admitted quite cheerfully that with more education he would have had no interest in these general symptoms. His intelegant moment lay in the question: why in the history of medicine had so little thought been given to the “syndrome of just being sick”. He observed later in life that it was only observation and deduction, and could have been made anytime after the Renaissance.

Even more ironically, his ideas were poo-poo’d by the supervising staff at medical school. Until ten years later. Like any good scientist he never forgot his Prague patients.

The scene now switches to Canada, where Selye lived the rest of his life. And he got lucky. His real interest by this time lay in the endocrine system. Think glands.

The clever thing about glands is they work whether there are nerve endings between organs or not. They are molecules that signal each other. You could say that the glands are the flight towers and the molecules the planes and they’re going from a specific airport to airport. They’re carried in the blood.

They include steroids, (Androgens, estrogens, glucocorticoids, mineralocorticoids, progestagens), peptides and proteins (Lots of amino acid residues including, for example, insulin from the pancreas, follicle-stimulation, and any hormone from the pituitary gland - more on that later), and the rather significant amines (Such as noreprephine, epriphene, dopamine, and throxine) which are floating around the brain and perform the marvelous trick of being neurotransmitters too. (They make the neurons fire across the synaptic gap and so create the electricity that makes our brains, well, conscious. Smart, huh!)

So Selye looked at these symptoms and the endocrine system. And had his Eureka! moment. Being a good scientist he did test it for on while on small, furry creatures, and his initial hunch was confirmed. Yes, hormone release, when thrown into overload causes the unhealthy symptoms of stress.

He had also observed that some general medical care seemed to help everyone: easily digestible foods, keeping the room at a comfortable temperature, relaxation etc;

The genius was to put it all together.

He recognised that stress symptoms were caused by the hormonal overload which was augmented by a non-caring environment.

That on it’s own was significant.

But luck and hard work really do make for good inductive reasoning. Selye was trying to hard isolate hormones in from the placenta at the time. Here, I’ll let Istvan Berczi tell the tale:

“For a while it was thought that the adrenal enlargement and involution of lymphoid organs was specific for a particular hormone, but attempts to purify it always failed as the activity was lost. At some point it occurred to Selye that this, in fact, could be a nonspecific response to noxious agents, and, indeed, when he performed the control experiments, that was the case. He published a short note about his findings in Nature in 1936. During the same year a longer article was published by him in The British Journal of Experimental Pathology, where he demonstrated that the involution of the thymus was in fact mediated by the adrenal gland as it was absent in adrenalectomized animals if stressed. His experiments in chickens revealed that the Bursa of Fabricius is also extremely sensitive to steroid hormones.”

In other words, he had found out that it was not one hormone, or even one gland, and that was what had been confusing everyone, but rather the work of a combination of glands. More work followed between 1936 and 1946, he published an overview as a paper The general adaptation syndrome and the diseases of adaptation in the Journal of Clinical Endocrinology, which identified the ternary causes of the hypothalamus-pituitary-adrenal glands all working together. A triple whammy as it were.

So here goes:

You get stressed because:

The hypothalamus (It is the base of your brain and acts as the link between the brain and the endocrine system)

talks to

The pituitary gland, which releases ACTH (Adrenocorticotrophic Hormone) into the bloodstream and is pea-sized and sits at the base of the brain and is responsible for control of homeostasis - ah!)

Which activates the adrenal glands, just above the kidneys, to release the villain of the piece, corticoids.

So that’s: Hypothalamus -> Pituitary -> ACTH -> Adrenal -> Corticosteroids

Hans Selye in 1974

So goodbye and thank you, Selye.

And hello, corticosteroids….. more on them tomorrow.

Day Two: Deeper Down The Rabbit-Hole: The Physiological Effects Of Stress