Paula has invisible “control of breathing” issues.
Control of breathing is part of the autonomic nervous system. Control of breathing and invisible problems with control of breathing is something that we have only begun to investigate…..because some people with control of breathing problems are unaware that they have this problem and are unaware of the risks they might face during their lifetime…..and one of these risks, Paula would argue…is reversible loss of self, thought, memory and mind, in the form of bipolar illness. No one can tell that Paula’s breathing is chronically abnormal, not even Paula. And yet her “bradypnea” is so extremely low at rest [with normal oxygen levels] that one wonders how it is that she is alive. Yet she is. And she has done well for most of her life, except when she required supplements of Paxil in order to avoid loosing her mind. Is there a connection between her abnormal yet invisible [till you check it out formally] control of breathing and super low resting breathing rate with active exhaling [a sign of laboured breathing] and her attacks of partial amnesia and mental confusion?
This hypothesis needs to be investigated, especially as it seems that a famous psychiatrist found abnormal vital signs, including breathing rate, depth and rhythm, in thousands of severe cases of unmedicated bipolar patients over 100 years ago [and no one listened].
Control of Breathing is a brain stem function. Is there a connection between Paula’s abnormal control of breathing and the importance of the serotonergic system to the control of breathing during development? Respir Physiol Neurobiol 2019 Dec;270:103255. doi: 10.1016/j.resp.2019.103255.Epub 2019 Jul 27. The serotonergic system and the control of breathing during development
- Is this why a serotonin agonist [helper] rescued Paula’s mind when she lost it [reversibly, it turns out].
Brain serotonin is released by the brain stem. The brain stem controls autonomic nervous system functions like blood pressure, breathing, heart rate, swallowing, digestion and arousal…seamlessly and without your conscious knowledge. Neurons producing serotonin are involved in a vital homeostatic function- control of breathing
Paula’s bipolar depression consisted mostly of the disappearance of her thoughts, of amnesia for her past and present thoughts ,of the disappearance of her knowledge and loss of her usual reactions. She remembered people and locations. She knew her name. She was amnesic for herself. She frantically worried about where her thoughts and knowledge went. She “forgot” the words that she needed to tell anyone so she simply said nothing and felt frantic.
Is there a link between Paula’s abnormal “control of breathing” and her partial amnesia, the loss of her ability to think?
No one knows. No one has looked at how many adults have invisible [till measured] “control of breathing ” issues, never mind if those issues are related to loss of ability to think.
Yet brain serotonin is important to “control of breathing”. And Paxil [a serotonin agonist] rescued Paula’s ability to think. [ Lithium [added to Paxil] eliminated the anxiety that accompanied the amnesia and loss of the ability to think or remember self.]
Paxil does not seem to change Paula’s breathing, it is still abnormally slow. But does it add something to her metabolism that is missing when she gets sick, perhaps something that goes missing periodically, say, after an infection which saps her energy and leaves her at risk of a bipolar depressive attack.
No one understands how serotonin helps breathing, yet it is definitely involved.
Serotonin (5-HT) was first discovered in the late 1940’s as an endogenous bioactive amine capable of inducing vasoconstriction, and in the mid-1950’s was found in the brain. It was in these early years that some of the first demonstrations were made regarding a role of brain 5-HT in neurological function and behavior, including some of the first data implicating reduced brain levels of 5-HT in clinical depression. Since that time, advances in molecular biology and physiological approaches in basic science research has intensely focused on 5-HT in the brain, and the many facets of its role during embryonic development, post-natal maturation, and neural function in adulthood continues to be established. This review focuses on what is known about the developmental roles for the 5-HT system, which we define as the neurons producing 5-HT along with pre-and post-synaptic receptors, in a vital homeostatic motor behavior – the control of breathing. We will cover what is known about the embryonic origins and fate specification of 5-HT neurons, and how the 5-HT system influences pre- and post-natal maturation of the ventilatory control system. In addition, we will focus on the role of the 5-HT system in specific respiratory behaviors during fetal, neonatal and postnatal development, and the relevance of dysfunction in this system in respiratory-related human pathologies including Sudden Infant Death Syndrome (SIDS). The serotonergic system and the control of breathing during development Kevin J. Cummings* and Matthew R. Hodges Respir Physiol Neurobiol. 2019 Dec; 270: 103255.
Keywords: development, serotonin, control of breathing
And surely breathing is necessary for thinking and self awareness and mind.
And even if we don’t understand it, surely..in Paula’s case, breathing and serotonin’s rescue of mind are related and should be investigated further.
Paula’s hidden [until measured] underlying biological dysfunction (e.g. damage to peripheral neutrons? 5-HT system defects?) causing her baseline slow breathing at rest may combine with an exogenous stressor (e.g. a virus, exposure to chronically higher levels of C02 or of mold or other allergen, loss of energy and nutrients after virus, ??? ) during a critical developmental stage eg. reaching one’s full height and reproductive status in young adulthood, reaching middle age with usual hormonal changes, or any hormonal changes ???] for adjustment of control systems to ultimately cause bipolar illness in humans.
Supplementation with Paxil, affecting the serotonin system, rescues the function of mind, thought and self memory in one person with control of breathing issues.
Interestingly, Paula has atrophied taste receptor cells. These cells are missing, and this is especially interesting because normally they regrow every month or so [but not for Paula]…AND these taste cells produce serotonin. Again, this is a hidden fact [unless one specifically looks and tests for reaction to salt/sugar]. Paula is not aware of this because she has normal taste function due to normal taste cells elsewhere in the mouth. We do not know about her serotonin pulmonary neuroendocrine cells or the serotonin cells in the GI tract or in the brain stem. [We do know that Paula’s MRI is normal – in normal health when taking supplemental Paxil and lithium- so Paula does not have the brain lesions that sometimes accompany “control of breathing” problems.]
Serotonin is primarily found in the enteric nervous system located in the gastrointestinal tract (GI tract). However, it is also produced in the central nervous system (CNS), specifically in the raphe nuclei located in the brainstem, Merkel cells located in the skin, pulmonary neuroendocrine cells and taste receptor cells in the tongue. Additionally, serotonin is stored in blood platelets and is released during agitation and vasoconstriction, where it then acts as an agonist to other platelets. https://en.wikipedia.org/wiki/Serotonin
Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. . It is essential in humans, meaning that the body cannot synthesize it and it must be obtained from the diet. Tryptophan is not only a precursor to the neurotransmitter serotonin, but also to the hormone melatonin, and vitamin B3. Many animals (including humans) cannot synthesize tryptophan: they need to obtain it through their diet, making it an essential amino acid. https://en.wikipedia.org/wiki/Tryptophan
Tryptophan hydroxylase (TPH) is an enzyme (EC 220.127.116.11) involved in the synthesis of the neurotransmitter serotonin. Tyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylase together constitute the family of biopterin-dependent aromatic amino acid hydroxylases. TPH catalyzes the following chemical reactionL-tryptophan + tetrahydrobiopterin + O25-Hydroxytryptophan + dihydrobiopterin + H2O It employs one additional cofactor, iron. https://en.wikipedia.org/wiki/Tryptophan_hydroxylase
So tryptophan needs to be obtained by what one eats and an enzyme [TPH] is required to synthesize it, with the help of iron.
In humans, the stimulation of serotonin production by administration of tryptophan has an antidepressant effect and inhibition of tryptophan hydroxylase (e.g. by p-Chlorophenylalanine) may precipitate depression. https://en.wikipedia.org/wiki/Tryptophan_hydroxylase
Future studies that clearly define the mechanisms by which 5-HT system and control of breathing and serotonin and tryptophan and TPH and iron may lead to depressive bipolar attacks – particularly mechanisms that involve self thought, self memory and sleep – might be a critical advancement for efforts aimed at developing a priori risk assessment and prevention strategies of bipolar illness.
Certainly, it seems likely that having hidden control of breathing issues would make it harder to co-ordinate metabolism, pH, thermoregulation, as well as finding and digesting and formulating all the essential amino acids necessary to stay alive, as well as maintaining the maximal function of those organs which need a lot of energy,[ the liver, the heart, the brain and the kidneys Am J Clin Nutr. 2010 Dec; 92(6): 1369–1377. . doi: 10.3945/ajcn.2010.29885].
Paula uses active inhaling and active exhaling [exhaling is passive] at rest. She uses more energy simply to breathe when staying still…she does not rest her respiratory muscles. Somehow, this suffices.
After periods of major illness and weight loss from illness, and as she ages.. it may not be that strange that she would need regular supplements of essential amino acids that seem especially important to brain function. And her hidden breathing problems may point to why she would require Paxil [and serotonin] rather than , say, thiamine, another nutrient necessary for normal function of the heart and of the mind, self thought and self memory or some other nutrient [eg iron] necessary for normal energy and mind function.
Measuring vital signs [BP,HR,RR and Body Temperature] at rest and looking for abnormal patterns will help in the search for nutrients which will restore and rescue mind, thought and memory and energy. It is all related. We have much to learn.