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High Cortisol And Low Testosterone Likely Drive PTSD

Discussion in 'Scientific Studies' started by haidut, Apr 23, 2019.

  1. haidut

    haidut Member

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    As the article below states, 20%+ of service members come back with PTSD. It is a devastating mental condition that makes patients not only unable to participate meaningfully in society but often drives them to violent and homicidal/suicidal behavior. Given the roles of cortisol and serotonin in driving violent psychotic behavior, the etiology of PTSD seems rather clear from a Peatarian perspective. And indeed, early studies in the 1980s provided solid evidence that cortisol is a causative factor in PTSD. However, due ghostwriting and general outcry from Big Pharma, the cortisol-PTSD link was disputed and the waters were muddied by often fake research questioning the connection between endocrinology and mental health. Well, it seems the cortisol connection is finally seeing the light of day again. As the study below shows, it is both elevated cortisol levels and low testosterone (T) levels that largely determine if somebody would develop PTSD or not. I think low T is not the only factor but rather in general the lack of anti-cortisol endogenous factors such as progesterone, DHEA, thyroid, pregnenolone, etc. So, it would be interesting to see the same study repeated and measurements for those other anti-cortisol hormones taken as well. But at least, this is a study is a long-overdue step in the right direction.

    https://www.sciencedirect.com/science/article/pii/S030645301630676X
    PTSD risk can be predicted by hormone levels prior to deployment, study says

    “…Up to 20 percent of U.S. veterans who served in Iraq and Afghanistan developed symptoms of post-traumatic stress disorder from trauma experienced during wartime, but new neuroscience research from The University of Texas at Austin suggests some soldiers might have a hormonal predisposition to experience such stress-related disorders. Cortisol — the stress hormone — is released as part of the body’s flight-or-fight response to life-threatening emergencies. Seminal research in the 1980s connected abnormal cortisol levels to an increased risk for PTSD, but three decades of subsequent research produced a mixed bag of findings, dampening enthusiasm for the role of cortisol as a primary cause of PTSD. However, new findings published in the journal Psychoneuro-endocrinology point to cortisol’s critical role in the emergence of PTSD, but only when levels of testosterone — one of most important of the male sex hormones — are suppressed, researchers said.”

    “…“Recent evidence points to testosterone’s suppression of cortisol activity, and vice versa. It is becoming clear to many researchers that you can’t understand the effects of one without simultaneously monitoring the activity of the other,” said UT Austin professor of psychology Robert Josephs, the first author of the study. “Prior attempts to link PTSD to cortisol may have failed because the powerful effect that testosterone has on the hormonal regulation of stress was not taken into account.”
     
  2. TheGoogler

    TheGoogler Member

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    This seems quite in line with my personal experience. I had chronically high stress for several years (still do to an extent, but not as bad now), which I believe has also led my T levels to suffer. Currently they are 400s range, and I am 21 and fit. Last year when I had much less regard for my health choices than I do now, I made some foolish decisions that led to a stimulant overdose in my workplace while in a severely sleep-deprived and paranoid state. Since then, I have dealt with severe PTSD symptoms stemming from the event. Prior to that I had no history of mental illness, no family history either.
     
  3. Momado965

    Momado965 Member

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    I think 11 oxo would work nicelt since it converts to keto testosterone and is a cortisol antagonist via the 11bhsd receptor. Wouldnt you agree? @haidut
     
  4. Terma

    Terma Member

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    Here's - let's say - a hypothetical situation where you could enter a state of PTSD, I just don't have the time to totally go into this or proof some of it better:

    You start off with high cortisol so eventually the GR feedback system gets desensitized. Then you get constant CRH and dynorphin release.

    High dynorphin leads to desensitization of the KOR receptors (not explained verbatim):
    Sci-Hub | Association of In Vivo κ-Opioid Receptor Availability and the Transdiagnostic Dimensional Expression of Trauma-Related Psychopathology. JAMA Psychiatry, 71(11), 1262 | 10.1001/jamapsychiatry.2014.1221

    This then lowers cortisol (as in that study) relative to before, because the KOR receptors normally can trigger cortisol release, and maybe you exhaust its release or break it down some other way as well:
    The effects of spiradoline (U-62066E), a κ-opioid receptor agonist, on neuroendocrine function in man

    [There is a gap of info in there, so it's still plausible cortisol could remain high, because depending on the rest - and the mechanism by which GR feedback sensitivity is lost - it might or might not matter]

    KOR is the system responsible for fear extinction - it has an important role even though it makes you temporarily feel like death.

    Also KOR normally stops the noradrenic and serotonin systems, meaning you end up with high CRH but nothing to stop the noradrenaline release, and nothing to extinguish fear memories.

    You have not enough material left to agonize the GR feedback receptor (I know that's redundant) and stop the stress loop, since both the ligands and the receptors are compromised, and probably the shuttling of the glucocorticoids to the nucleus is all messed up. Hence the abortion drug

    In another study (I don't have the link on me), the GR feedback receptor is responsible for endocannabinoid release, which throttles NMDA and other stuff in that brain area. (My guess is astrocytes try to increase kynurenic acid to make up with NMDA antagonism, but that might not apply in this disease.) So they all end up smoking weed.

    Testosterone offsets the dopamine-killing activity of the period when dynorphin is high but KOR is not yet downregulated. But if it just stops cortisol/GR from dysregulating (don't have time to read mechanism) then of course it will keep the loop from beginning, my guess.

    Propranolol I won't have time to find it, but if you go by the effects of midazolam, midazolam can increase dynorphin in the hypothalamus of animals:
    Effect of chronic treatment with morphine, midazolam and both together on dynorphin(1-13) levels in the rat. - PubMed - NCBI
    Meaning it could temporarily surmount the low KOR abundance with higher dynorphin above baseline and achieve fear extinction, though on that basis you would never want to take that chronically.

    Probably there's yet another link between KOR and noradrenaline/adrenaline in there. I had to write this fast so this is incomplete and poorly checked, I expect some part of this to be off, but it's just to show there's a big link missing in these stories... but it's almost there!

    (The other study with propranolol was this but I'll need to find time to understand it better:
    Locus Coeruleus Kappa-Opioid Receptors Modulate Reinstatement of Cocaine Place Preference Through a Noradrenergic Mechanism )
     
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