Patterns of behaviour are important clues, especially in illness.

In my opinion, patterns of behavior [including the behavior of thinking and emotion] in illness, point to possible underlying physiological problems.

Any behavior which reduces appetite, feeding behavior ,weight and locomotor activity and sleep is significant and needs to be looked at closely. Kraepelin understood these behaviours to reflect an issue with the metabolism of the patient. Metabolism is a function of the autonomic nervous system. [see https://www.merckmanuals.com/en-ca/home/brain,-spinal-cord,-and-nerve-disorders/autonomic-nervous-system-disorders/overview-of-the-autonomic-nervous-system below] .

Kraepelin, towards the end of his long career, figured out that since metabolism was disturbed in manic depressive insanity and metabolism was known to be organized by the autonomic nervous system [which runs without our conscious knowledge of its workings] then perhaps the other physical signs that the A.N.S. [autonomic nervous system] manages should be measured in unmedicated bipolar patients, giving him more clues to work with.

As the paper reproduced below, for your convenience , [https://www.merckmanuals.com/en-ca/home/brain,-spinal-cord,-and-nerve-disorders/autonomic-nervous-system-disorders/overview-of-the-autonomic-nervous-system%5D makes clear, the A.N.S is responsible for determining our blood pressure, our heart rate, our breathing rate and our body temperature and more.

The vital signs [blood pressure, our heart rate, our breathing rate and our body temperature] are easy to measure in first episode unmedicated patients even back in 1925. The vital signs can give us important information on how well the autonomic nervous system is working, especially if you are familiar with the normal working of its sympathetic nervous system response to stress.

What Kraepelin found was astonishing ! Kraepelin found that the sympathetic nervous system response to stress was broken and could not possibly do a good job of protecting the body or brain during certain metabolic stressors requiring a normal sympathetic stress response.

Metabolic stressors such as some viruses, vitamin deficiencies, undernutrition [due to illness or due to the effects of poverty], or due to the effects of blood loss, or due to the effects of extreme temperatures, or due to the effects of major developmental hormone change [puberty, menopause, old age] , or due to the effects of chronic exposure to chronic periods of insufficient oxygen levels or excessive carbon dioxide levels due to *** heating or cooking fuel combustion in indoor air or [more likely], effects of some combination of all of these these. *** [” three fuels—wood, agricultural residues, and coal—constitute the solid cooking fuels used by about 40 percent of humanity today (Bonjour and others 2013). Typically burned in simple cookstoves, these fuels produce smoke that is now understood to cause a large burden of disease (Smith and others 2014). Washington (DC): The International Bank for Reconstruction and Development / The World Bank; 2017 Oct 27. Injury Prevention and Environmental Health, 3rd edition Disease Control Priorities, Vol. 7 Editors: Charles N. Mock, Rachel Nugent, Olive Kobusingye, and Kirk R. Smith. Chapter 7 Household Air Pollution from Solid Cookfuels and Its Effects on Health Kirk R. Smith and Ajay Pillarisetti. https://www.ncbi.nlm.nih.gov/books/NBK525225/

Kraepelin found that blood pressure was very elevated in and that heart rate was elevated as well. These are indications of increased sympathetic nervous system activation.

Current research studies are finding the same results as Kraepelin, – signs of sympathetic nervous system activation — in a subset of patients with major depression.– and I suspect that this subset of patients will be found to have bipolar depression. Look at the conclusions of the research paper below:

” Conclusions: We have identified a subset of patients with MDD in whom sympathetic nervous activity is extraordinarily high, including in the sympathetic outflow to the heart. Treatment with an SSRI may reduce sympathetic activity in a manner likely to reduce cardiac risk. “ Sympathetic activity in major depressive disorder: identifying those at increased cardiac risk? Brenchley, Florentia Socratous, David M Kaye, Markus P Schlaich, Ian Hickie, Gavin W Lambert David A Barton ¹, Tye Dawood, Elisabeth A Lambert, Murray D Esler, Deepak Haikerwal, Celia J Hypertens 2007 Oct;25(10):2117-24. doi: 10.1097/HJH.0b013e32829baae7.

What is the main function of the sympathetic nervous system activation? [https://www.merckmanuals.com/en-ca/home/brain,-spinal-cord,-and-nerve-disorders/autonomic-nervous-system-disorders/overview-of-the-autonomic-nervous-system%5D Merck Manuals informs us that “Generally, the sympathetic division does the following: It prepares the body for stressful or emergency situations—fight or flight. But what if one has suffered some injury that prevents the sympathetic nervous system from functioning normally.

Stress can be psychological and/or metabolic [physical] , and the sympathetic nervous system will respond to both. The sympathetic nervous system reacts reflexively, unconsciously and fast. The sympathetic nervous system cannot tell us what, if anything, is wrong with itself or its response due to issues within the body, the brain, the organs, the muscles, the metabolism , etc…The sympathetic nervous system is part of the autonomic nervous system and simply reacts or tries to and this feature of the autonomic nervous system has no language except to raise the alarm and overcome us with anxiety and distress and unpleasant feelings. Which we ignore at our peril!

Chronic activation of the sympathetic nervous system is serious and I do not think that chronic stress is due to a faulty alarm system. Chronic activation of the sympathetic nervous system means that something is really wrong and must be investigated.

Sympathetic nervous system arousal will usually cause the heart rate to rise, the blood pressure to rise, the breathing rate to rise and would – I think, at least maintain normal thermoregulation.

In the bipolar depressed patients that Kraepelin investigated, he found that not only did breathing rate NOT rise as would be normal when the sympathetic nervous alarm sounds, but the breathing rate was abnormal slow or otherwise abnormal. The breathing rate is responsive to the effects of stress, same as the blood pressure and the heart rate and like them , depends on the actions of smooth muscle, skeletal muscle and cardiac muscle. If indeed the breathing rate is not responding normally to the presence of certain stressors or combination of stressors, this must be 1] acknowledged and 2] further investigated.

And Kraepelin also found that not only was thermoregulation NOT normal [in the depressive stage of manic depressive insanity], but that body temperature was lower than normal.

And not only did the muscles of the body NOT get more blood through vasodilation, in order to help a person run away or get ready to fight , but Kraepelin found that the extremities of the body – the hands and feet and lips- were pale, cold and even blue, suggesting vasoconstriction [a response to bleeding and/or hypothermia].

The patients reported extreme and chronic distress and anxiety and fear and dread which is expected when the sympathetic nervous system alarm is triggered. The patients could not explain what was wrong with them, partly because they did not know what was wrong and partly because the brain was not able to function properly due to mental confusion and because responses to metabolic stressors are not accessible to the cognitive or verbal parts of the brain because they are part of the autonomic nervous system which operates below our cognitive radar. This system is easy accessed through measurement of the 4 major vital signs I have already mentioned, especially breathing rate because of its relationship with acid base of tissues and organ systems of the body, including blood.

Despite the triggering of the sympathetic nervous system, Kraepelin found that bipolar depressed patients could not raise their breathing rate as required and they had difficulty maintaining their body temperature and THIS seems to be the emergency that the sympathetic nervous system is signalling !

Kraepelin’s findings [in unmedicated patients ] need to be followed up. Can we find the same in bipolar depressed unmedicated [preferable] patients today? Medication are chemicals and they change the vital signs, often in predictable patterns [look up toxidromes to get a general idea], so pure data requires [ideally] unmedicated patients. It is vital to see whether Kraepelin’s findings can be replicated! Because if they do stand up to the test of time and experimental research investigation, his findings are a very important part of the manic depressive puzzle and a possible gateway to a more successful treatment plan.

The sympathetic nervous system manages the metabolism of the person unconsciously. It does this automatically when something threatens the life and health of its owner. In order to properly understand whether the threat is psychological or metabolic, the function of the sympathetic nervous system itself MUST be investigated, by immediately measuring the vital signs of a person who is not themselves, who is lethargic and depressed, and who reports major distress.

The measurement of the vital signs is the measurement of the sympathetic nervous system. And Kraepelin found that management of the stress response of the vital signs was broken and the sympathetic nervous system was signalling an injury to itself !

And we have not been listening to it !

Instead we have been listening to and noting and analyzing the behaviours without knowing whether the function of the autonomic nervous system is normal or not, broken or not, in need of our 21st century supportive medical techniques and medicines [eg antibiotics] or not!

Despite the severe symptoms accompanying bipolar depression [and we have not yet mentioned the physical signs Kraepelin found in mania], no one, even today, bother to investigate whether the stress response is able to maintain proper homeostasis or not under the stress of certain physical and metabolic stressors we all face.

And without being able to control the breathing rate or maintain normal body heat, the sympathetic nervous system is signaling that it, itself, is under major stress and that the organism is in deep trouble!

This is the reason for the extreme distress, the brain dysfunction, the heightened blood pressure and heart rate in reversible attacks of manic depressive insanity. And we do have modern treatments that will help the sympathetic nervous system to recover from these stressors, once we understand that it is the nervous system itself, in particular the sympathetic nervous system, that needs help to recover from the metabolic stressor it can no longer deal with. If we measure the unconscious vital signs then we will finally be listening to the language of the broken sympathetic nervous system that is doing the best it can, given its broken and injured parts that are preventing normal defence of our chemical defences of our organs and tissues .

If Kraepelin’s studies are replicated, then we will understand that the problem that the sympathetic nervous system is yelling about is its inability to regulate the ventilatory system properly, when it becomes necessary under conditions of infection, inflammation, or exposure.

This is the reason for the chronic stress, the dysphoria, the misery, the range of mental dysfunction. And breathing rate regulation is handled by the autonomic nervous system and we are unaware of it, it is unconscious, even when it is abnormal.

The vital signs are coordinated by the autonomic nervous system which is able to communicate information between the body and the brain in order to keep metabolism running properly.

The autonomic nervous system is made up of neurons and balances signals from the sympathetic nervous system and the parasympathetic nervous system.

TO BE CONTINUED AND EDITED!!!!

I finally figured it out!!!

Overview of the Autonomic Nervous System

By Phillip Low  https://www.merckmanuals.com/en-ca/home/brain,-spinal-cord,-and-nerve-disorders/autonomic-nervous-system-disorders/overview-of-the-autonomic-nervous-system

, MD, College of Medicine, Mayo Clinic

Last full review/revision Sep 2021| Content last modified Sep 2021

The autonomic nervous system regulates certain body processes, such as blood pressure and the rate of breathing. This system works automatically (autonomously), without a person’s conscious effort.

Disorders of the autonomic nervous system can affect any body part or process. Autonomic disorders may be reversible or progressive.

Anatomy of the autonomic nervous system

The autonomic nervous system is the part of the nervous system that supplies the internal organs, including the blood vessels, stomach, intestine, liver, kidneys, bladder, genitals, lungs, pupils, heart, and sweat, salivary, and digestive glands.

The autonomic nervous system has two main divisions:

• Sympathetic
• Parasympathetic

After the autonomic nervous system receives information about the body and external environment, it responds by stimulating body processes, usually through the sympathetic division, or inhibiting them, usually through the parasympathetic division.

An autonomic nerve pathway involves two nerve cells. One cell is located in the brain stem or spinal cord. It is connected by nerve fibers to the other cell, which is located in a cluster of nerve cells (called an autonomic ganglion). Nerve fibers from these ganglia connect with internal organs. Most of the ganglia for the sympathetic division are located just outside the spinal cord on both sides of it. The ganglia for the parasympathetic division are located near or in the organs they connect with.

Function of the autonomic nervous system

The autonomic nervous system controls internal body processes such as the following:

• Blood pressure
• Heart and breathing rates
• Body temperature
• Digestion
• Metabolism (thus affecting body weight)
• The balance of water and electrolytes (such as sodium and calcium)
• The production of body fluids (saliva, sweat, and tears)
• Urination
• Defecation
• Sexual response

Many organs are controlled primarily by either the sympathetic or the parasympathetic division. Sometimes the two divisions have opposite effects on the same organ. For example, the sympathetic division increases blood pressure, and the parasympathetic division decreases it. Overall, the two divisions work together to ensure that the body responds appropriately to different situations.

Autonomic Nervous System

Generally, the sympathetic division does the following: 

• Prepares the body for stressful or emergency situations—fight or flight

Thus, the sympathetic division increases heart rate and the force of heart contractions and widens (dilates) the airways to make breathing easier. It causes the body to release stored energy. Muscular strength is increased. This division also causes palms to sweat, pupils to dilate, and hair to stand on end. It slows body processes that are less important in emergencies, such as digestion and urination.

Sympathetic Innervation

The parasympathetic division does the following:

• Controls body process during ordinary situations.

Generally, the parasympathetic division conserves and restores. It slows the heart rate and decreases blood pressure. It stimulates the digestive tract to process food and eliminate wastes. Energy from the processed food is used to restore and build tissues.

Parasympathetic Innervation

Both the sympathetic and parasympathetic divisions are involved in sexual activity, as are the parts of the nervous system that control voluntary actions and transmit sensation from the skin (somatic nervous system).

[to be continued]………