Chronic stress increases level of a protein that decreases availability of mood-regulating chemical
on 30 August 2021
Chronic stress, when the cracks appear

As a general rule, when working with a client, for any condition, I always look for the potential for stress and/or anxiety in any presenting issue. The rationale being, that stress and anxiety are known to limit or inhibit normal brain function. It is always going to be more difficult to help anyone when their brain isn't firing on all four cylinders! The research below adds a little weight to my treatment philosophy, as well as a clearer picture of the WHY factor . . . 


 The chemical correlates lurking behind the stress response

The main component that seems to be running amok here is transglutaminase 2 (TG2), which leads to a lack of BDNF (Brain-derived neurotrophic factor). BDNF is found in several places in the brain but perhaps, for me, the most interesting is the hippocampus, cortex, and basal forebrain. These areas are crucially involved in memory, learning, and higher thinking (our executive function). It seems obvious. Therefore, if something is impeding memory formation, storage, retrieval, this will affect the way we experience life; both on a daily basis and over the longer term. When it comes to depression, the absence of normal function in these areas of the brain is a major factor in the negative feeling towards life and living. Science predominantly points towards advancing pharmaceutical intervention, albeit occasionally referencing therapeutic ones. However, my focus is on how can we use, what I refer to as, the anomalous structure we call the mind. I take this position, on the mind, because so many hypnotherapists feel that they tap into it and/or change it. In reality, for any change to occur, at the human/behavioural level, change has to occur within the brain itself.  I refer to the 'minds,' in the factual way they are posited, i.e. hypothetical - philosophical constructs, a unique neuro-communication system that uses language by way of an inter/intra-communication portal. Because of that, the use of the word 'mind' is an extremely useful way of explaining our awareness. The awareness of now, that we are alive, experiencing both phenomena and noumena, as well as an awareness that there are things that we are unaware of!

When it comes to stress, it is a mistake to believe that it is but one thing, stress is both natural and necessary and without it, life could not exist. So I absolutely balk at the idea of some people advertising the promise of a stress-free life it's like advertising a death sentence! Of course, when people refer to stress, they are referring to distress - psychological stress. However, there are many forms of stress and all playing a part in keeping us alive but also at risk of becoming out of sync. Apart from psychological stress, there is oxidative (environmental) stress, metabolic stress, osmotic stress and heat-shock stress (regulation thru upregulation). When it comes to working with stress, it helps to know what type it is, what may be causing it and, from there, an appropriate intervention. The objective in treating stress is not to remove it but rather, to help the client regulate it towards it becoming a normally functioning life support system!

Obviously, at least I hope it is obvious, it helps by doing all we can to reduce, or ideally, remove as many stressors as possible. In that context, Hypnosis is essentially akin to mind engineering. By that I mean, using this unique communication system, referred to as 'mind,' we promote the process of change. But, what changes? Essentially it is the ways in which memories express themselves and life, in many senses, is the consequence of memory expression. The primary ways that changes to memory expression occur, are through the use of language, this can alter perspective, perception, and eventually the chemical architecture of specific networks. What we term a change of mind, is the outcome of the change that occurs in neurons and networks of neurons. From a linguistic perspective, the conscious awareness of these phenomena are described through thoughts! Consequential to these shifts, our thoughts transition to become changes in behaviour and lead us towards reacting differently. And that changes life itself! Anyway, the takeaway from this is, do all you can to limit unnecessary stress and anxiety. We actually need a certain amount of stress and anxiety to keep us safe, so the objective, as stated above, is never to eliminate it but rather, learn from the experience and to then use it to our advantage.

The objective here is to help people understand how and why we become illogically trapped into irrational emotional experiences that may actually be happening for reasons different to that which we would imagine! If you want to know more about how Hypnotherapy can help you; why not make an appointment for a Free Consultation?

For more information on the Free Consultation - go here or, to book your Free Consultation today, you can do that here

The Research:
Scientists have found elevated levels of transglutaminase 2, or TG2, in the brains of mice experiencing chronic stress -- an animal model of depression -- as well as the prefrontal cortex of depressed people who committed suicide. High TG2 levels in the mouse translated to atrophy of neurons, depression-like symptoms and reduced levels of TrkB, the receptor for brain-derived neurotrophic factor, a brain-nourishing molecule that also aids connectivity, said Dr Anilkumar Pillai, a neuroscientist in the Department of Psychiatry and Health Behaviour at the Medical College of Georgia at Augusta University.

When scientists overexpressed TrkB, it relieved the depression-like symptoms in their animal model. "If you don't have enough BDNF, then all the serotonin in the world won't help," said Pillai, corresponding author of the study in the Nature journal Molecular Psychiatry. Likewise, when they directly reduced TG2 levels using a drug or a viral vector, more BDNF signalling occurred and depressive symptoms abated, said Pillai, who suspects that the protein may be a powerful new target in the fight against depression. They found TG2 levels increased in their animal model following administration of stress hormones and after several weeks of actual stress that mimics the lives of chronically stressed individuals. Both produced classic depressive behaviour and increased TG2 levels in the prefrontal cortex, a region involved in complex thoughts, decision-making as well as mood and personality expression.

Serotonin is a major neurotransmitter in the brain involved in many functions, including mood regulation. Serotonin levels in a depressed patient's blood should be high because serotonin signalling in the brain is low, Pillai said. Blood levels can be used to help diagnose the condition that affects about 350 million people worldwide and is the leading cause of disability, according to the World Health Organization. Many cell types make serotonin. Interestingly, the vast majority of serotonin is made in the gut, but neurons do make some of their own, Pillai said. Astrocytes make BDNF, whose levels are also low in depression. Although just how the two work together is an unfolding mystery. In this study, Pillai and his team further linked them by showing that treatment that increases serotonin availability -- as most antidepressants do -- also increased levels of the BDNF receptor thru the action of RAC1. TG2 converts serotonin to RAC1, a protein that helps rejuvenate the BDNF receptor, TrkB.

Now the MCG scientists have shown that in depression a healthy balance of all these is upset, as elevated TG2 makes less serotonin available, leaving insufficient levels to enable proper communication between neurons. The brain also is more vulnerable as the increased level of activated RAC1 is inexplicably degraded, which leads to less instead of more BDNF signalling. "Increased amounts of TG2 will eventually lead to decreased levels of RAC1, and BDNF signalling is just not happening," Pillai said. The next steps include looking for other drugs that lower TG2 levels. For the study, researchers used cysteamine, whose clinical uses today include treatment of a rare genetic condition in which a buildup of crystals can cause kidney failure. Unfortunately, the drug creates an odour that has patients bathing multiple times daily. They also want to directly measure serotonin levels following treatment, although Pillai notes that increased BNDF signalling should be significant to alleviate symptoms.

Story Source:
The above post is reprinted from materials provided by the Medical College of Georgia at Augusta University. Note: Content may be edited for style and length.

Journal Reference:
1. C D Pandya, N Hoda, A Crider, D Peter, A Kutiyanawalla, S Kumar, A Ahmed, G Turecki, C M Hernandez, A V Terry, A Pillai. Transglutaminase 2 overexpression induces depressive-like behaviour and impaired TrkB signalling in mice. Molecular Psychiatry, 2016; DOI: 10.1038/mp.2016.145