Energy saving state; depression.

Either Paula’s broken breathing caused her difficult birth or her difficult birth caused her broken breathing. I think that Paula got stuck in her Mother’s crooked pelvis [Mom had Rickets as a child and this deformed the bones of her lower body] and Paula nearly asphyxiated to death. She was saved by her doctors and grew to be smart, fit and completely normal. I do think though, that her near asphyxiation led to be hypoxia tolerant. Paula breathes less air per minute than most other people. Her breathing rate is 3-5 breaths per minute at rest when healthy and fit and smart. I think that Paula got sick when she had a short period of anoxia in her sleep. She woke up with a start, very scared. I think that this uncommon scenario resulted in a cascade of physiological reactions. Paula was unable to raise her breathing rate after her period of anoxia, as would be normal. And thus she was in an in-between state of existence, thrust into an “energy saving state” where all functions that are not essential for homeostasis are “muted”. Toned down. Things like mind, thoughts, working memory, locomotor activity, behaviour, ….all muted…in order to keep just enough energy for heart function[which is still disturbed] and brain stem function andjust enough function of the kidneys, liver, etc….just survive…

Using Oxygen to Release Energy

How does cellular respiration occur in mitochondria? The matrix is filled with water and proteins (enzymes). Those proteins take organic molecules, such as pyruvate and acetyl CoA, and chemically digest them. Proteins embedded in the inner membrane and enzymes involved in the citric acid cycle ultimately release water (H2O) and carbon dioxide (CO2) molecules from the breakdown of oxygen (O2) and glucose (C6H12O6). The mitochondria are the only places in the cell where oxygen is reduced and eventually broken down into water. 

Mitochondria are also involved in controlling the concentration of calcium (Ca2+) ions within the cell. They work very closely with the endoplasmic reticulum to limit the amount of calcium in the cytosol.

It seems obvious that the amount of air a person takes in per minute will affect the cellular respiration in the mitochondria directly. Yet no one seems to be studying respiratory rate at rest or minute ventilation. Decreasing the citric acid cycle because of the lack of availability of oxygen and glucose will directly decrease the amounts of water and carbon dioxide. This is good of it keeps the ratio of oxygen to carbon dioxide manageable and less acidosis in the blood. Acidosis is bad. It is dangerous. Keeping levels mild is good. Even if it means “muting” voluntary activity, non essential organ activity, and functions of the mind in favour of the regulation of the brain stem, the heart and homeostasis then so be it.

It is possible that people that have survived significant anoxic periods at birth, people like Paula, may have developed hypoxia tolerant defences when suffering further anoxic periods. And it is possible that these people have slow deep breathing rates at rest as a result of subtle injuries birth and that this slow deep breathing is protective against permanent injury to the brain during periods of neuromuscular weakness and respiratory pump failure in adulthood.

Of particular interest are naturally evolved adaptations that modify mitochondrial function to 1) provide metabolic plasticity related to the control of cellular energetics at varying oxygen tensions, and that 2) proactively initiate neuroprotective mechanisms. Studies of species that are highly tolerant to hypoxia and anoxia provide prime examples of these central roles for mitochondria in signaling oxygen variability and subsequently coordinating cellular responses to hypoxia. Indeed, mitochondria are the lynchpin of aerobic metabolism, consuming > 90% of the body’s oxygen to facilitate oxidative phosphorylation, which is the process via which ATP is formed through the transfer of electrons along the complexes of the electron transport chain (Pamenter, 2014). This central role in aerobic energy production makes mitochondria an excellent sensor of changes in cellular oxygen tension. Furthermore, mitochondria also coordinate neuroprotective pathways that respond to low oxygen challenges in brain of hypoxia-tolerant species. These pathways mediate diverse responses including changes in transcriptional activity, organelle and synaptic function, and intercellular communication (Pamenter, 2014). For example, carefully regulated reactive oxygen species and Ca2+ signaling beneficially modulate neuronal proteins to limit ion flux in anoxia-tolerant freshwater Western painted turtle brain [Chrysemys picta bellii], preventing excitotoxic cell death during prolonged anoxic or ischemic exposures (Pamenter, 2014; Hogg et al., 2015). Conversely, in brain of hypoxia-intolerant mammals, unregulated reactive oxygen species generation and/or deleterious mitochondrial Ca2+ accumulation initiate cell death pathways during hypoxic or ischemic challenges (Kalogeris et al., 2014). Therefore, mitochondria are at the center of neuronal energy production in normoxia but also determine the cellular fate choice between initiating neuroprotective responses vs. activating cell death cascades when oxygen is limited. Neural Regen Res. 2016 May; 11(5): 723–724. doi: 10.4103/1673-5374.182690PMCID: PMC4904454PMID: 27335547 Comparative insights into mitochondrial adaptations to anoxia in brain Matthew E. Pamenter, Ph.D.*

But it is excessively unpleasant for human beings to experience.

This is what Paula thinks happened to her. It seems that serotonin agonists help to prevent death and further neuromuscular deterioration and helps regulate calcium levels. It does not fix the problem with breathing too slowly but may somehow reduce the calcification of the rib cage, making ventilation less difficult and preventing further episodes of anoxia. We will not know for sure without research. But in order to do this research we need to change out ideas and our clinical approach. We need to know when too slow breathing is causing episodes of depressive insanity, deriving from adaptive switches to low oxygen states by the mitochondria.

We also know from Paula’s experience and from Kraepelin’s studies of depressive and manic attacks, that unmedicated patients almost always spontaneously recover normal brain function and normal behaviour, although it can take decades without supportive medical care.


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