Depression as Hibernation? Nope.

Some researchers have suggested that depression is a type of hibernation. “Metabolic depression, an adaptive biological process for energy preservation, is responsible for torpor, hibernation and estivation. We propose that a form of metabolic depression, and not mitochondrial dysfunction, is the process underlying the observed hypometabolism, state-dependent neurobiological changes and vegetative symptoms of major depression in humans. ” John A Tsiouris PMID: 16061329 DOI: 10.1016/j.mehy.2005.05.044 Metabolic depression in hibernation and major depression: an explanatory theory and an animal model of depression 2005;65(5):829-40. doi: 10.1016/j.mehy.2005.05.044.

What is hibernation exactly? Paula and I looked it up and found this concise definition in the Royal Society of Chemistry.

Hibernation

Definition: Any process in which an organism enters and maintains a period of dormancy in which to pass the winter. It is characterized by narcosis and by sharp reduction in body temperature and metabolic activity and by a depression of vital signs. https://www.rsc.org/publishing/journals/prospect/ontology.asp?id=GO:0042750&MSID=B901972N

As Paula can tell you and as Kraepelin learnt from his bipolar depressed patients and ask any person who has suffered from significant depressive attacks, depression may LOOK LIKE hibernation from the outside, but if sufficiently severe, it is experienced internally as life or death AROUSAL. This is the reason for the sympathetic arousal Kraepelin and I found during depressive attacks. Blood pressure was very elevated, as was heart rate and there were intermittent murmurs and arrhythmia’s. This is very different than hibernation.

The only vital signs that were depressed were indeed, body temperature, which was mildly decreased at rest, and breathing rate, which was abnormally slow and deep with use of accessory muscles [abdominal muscles mostly].

This presentation of vital signs and heightened internal arousal and fear suggests a problem with the respiratory pump mechanism and perhaps some obstruction or possibly infection.

The patient usually does not understand that their ventilatory ability to respond to respiratory emergencies is limited and is instead miserable and fearful. They do not have enough energy for normal activity and are mentally slowed and mentally confused, most likely due to respiratory acidosis causing hypercapnia, although this should be studied carefully in order to be sure.

Episodes of anoxia can trigger all kinds of physiological changes that we are only beginning to understand; Paula and I think that these are the kinds of things that we must look into when considering what happens in depressive episodes.

Hypoxia triggers several mechanisms to adapt cells to a low oxygen environment. Mitochondria are major consumers of oxygen and a potential source of reactive oxygen species (ROS). In response to hypoxia they exchange or modify distinct subunits of the respiratory chain and adjust their metabolism, especially lowering the citric acid cycle. Intermediates of the citric acid cycle participate in regulating hypoxia inducible factors (HIF), the key mediators of adaptation to hypoxia. Here we summarize how hypoxia conditions mitochondria with consequences for ROS-production and the HIF-pathway. Redox Biol. 2017 Aug; 12: 208–215.Mitochondrial composition and function under the control of hypoxia Dominik C. Fuhrmanna and Bernhard Brünea,b,⁎

Scientists are just beginning to learn about the role of the mitochondria in human biology. Paula and I think that that intermittent bouts of anoxia or hypoxia must “turn on” an evolutionarily conserved mechanism involving the HIF-pathway. Perhaps this biological mechanism switches on in response to short periods of anoxia during too slow breathing rate at rest or in sleep. Perhaps the too slow breathing is the result of this mechanism being turned on. What happens if there is a period of anoxia during normal breathing rates at rest or during sleep?

Paula and I may have insight into this as well. We discussed this one day with another colleague who has sleep apnea. Let this discussion be the topic of our next blog post.