Cortisol (stress) Directly Causes Depression

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

  1. haidut

    haidut Member

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    I have posted quite a few threads/posts on the role of stress as perhaps the main cause of depression and other mental disorders. Officially, psychiatry claims that no environmental factor is known to be a direct cause of depression and that depression is a “complex” mix of genetic predispositions possibly “facilitated” by an environmental factor. Yet, in every animal model known to science and used to study depression, regimens like chronic unpredictable mild stress (CUMS) and chronic social defeat (CSD) are used as the sole and direct causes of depression in the animals. No talk of genes whatsoever in those animal models. Medicine dismisses CUMS and CSD as too “complex” in nature to ascribe to a single factor like a steroid. Genes are again invoked and the main theme continues to be that there is no direct evidence implicating stress as a cause of depression. Well, no more. The study below does away with CUMS/CSD and instead of subjecting the animals to stress it makes them depressed by administering cortisol directly. Even more shockingly, the cortisol dose administered was physiological - HED of just 1mg/kg daily. For comparison, when a person is under severe stress she/he can produce endogenously 500mg+ daily.

    Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation

    “…We began by testing whether the induction of depression-related behavior in chronic stress models is associated with targeted effects on specific dendritic spine populations. To this end, we imaged the PFC through a prism (13, 16) chronically implanted in the contralateral hemisphere (Fig. 1A). Using two-photon (2P) laser-scanning microscopy, we obtained high-resolution images of the apical dendrites of yellow fluorescent protein (YFP)–expressing projection neurons in the medial PFC (mPFC) [in Thy1/YFP-H mice (Jackson Labs)] before and after 21 days of exposure to corticosterone (CORT) (0.10 mg/ml in the drinking water) (21), the principal murine stress hormone (Fig. 1A). CORT is a critical mediator of chronic stress effects on behavior, and chronic CORT treatment recapitulates important aspects of the neuroendocrine response to chronic stress (2126).”

    Ketamine May Relieve Depression By Repairing Damaged Brain Circuits

    “…So Liston and a team of scientists from the U.S. and Japan gave mice a stress hormone that caused them to act depressed. For example, the animals lost interest in favorite activities like eating sugar and exploring a maze. Then the team used a special laser microscope to study the animals’ brains. The researchers were looking for changes to synapses. “Stress is associated with a loss of synapses in this region of the brain that we think is important in depression,” Liston says. And sure enough, the stressed-out mice lost a lot of synapses. Next, the scientists gave the animals a dose of ketamine. And Liston says that’s when they noticed something surprising. “Ketamine was actually restoring many of the exact same synapses in their exact same configuration that existed before the animal was exposed to chronic stress,” he says. In other words, the drug seemed to be repairing brain circuits that had been damaged by stress.”

    Moreover, the study exposes another fraudulent meme commonly propagated by doctors – i.e. that steroids are not effective when administered orally – by causing depression through administration of cortisol in the drinking water. The study also suggests that the rapid antidepressant effects of the recently approved ketamine are likely due to being a functional or maybe even direct glucocorticoid antagonist. This is a mechanism of action for ketamine I have never heard discussed officially, possibly because it may undermine steroid sales and widespread use in hospitals. Instead, we are being fed the usual crap of ketamine having a “complex” mechanism of action that is mostly unknown at this point.
    https://www.sciencedirect.com/science/article/pii/S0166432818314451)

    And if all the above damning findings were not enough, there is evidence that ketamine also acts against another major mediator of stress – serotonin. The very chemical that we have been told for decades is a “cure” for depression, a “happiness hormone” that tens of millions of people in the US alone are prescribed for life in the form of toxic serotonergic (SSRI) drugs.
    https://www.researchgate.net/public..._serotonin_in_the_central_effects_of_ketamine
     
  2. Murtaza

    Murtaza Member

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    Can pizotifen be taken for stress if say cypro is not available? Would it have an effect on cortisol?
     
  3. Cirion

    Cirion Member

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    I agree. It ruined my health in childhood and early adulthood. I was stressed for 2 decades straight, being perfectionist in school always wanting a 4.0 GPA, having bad habits like staying up all night, having poor diet...

    I find the hard part is once you have been stressed this long like me, that it's very hard to break the cycle, and your tolerance to stress also becomes VERY small. For example I had pretty extreme anxiety about the prospect of getting a tooth filled (if you can't tell I HATE dentists lol) to the point where I was considering sedation. It doesn't help I have some horrific memories of dentists... but that's a story for another thread lol.
     
  4. Regina

    Regina Member

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    :thumbsup: all great finds haidut!
    I think "chronic social defeat' is pitiful. It is despicable when good people are bullied into a demoralized depressed state by demoralized people. The whole sad process is nauseating. But these findings are hopeful for reversing such appalling waste.
     
  5. Rafael Lao Wai

    Rafael Lao Wai Member

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    I agree. I would say that is the case especially in schools. And it's a habit that is apparently socially acceptable, since people who try to end the bullying( by asking for the help of a teacher or an adult) are seen as weak and made fun of. In american movies, the bullying theme is very common, and it probably reflects the degree to which the american society has degenerated. All the PUFA, SSRI's, lack of sleep, malnutrition, lack of freedom and also living one's life without purpose, as well as a few other things( like fluoride in the water, pesticides etc.) give rise to the sad society we have today, where even children are very sick.

    Wow, I didn't know people could even make that much cortisol! No wonder why so many people have heart attacks. If cortisol can dissolve skeletal muscle, it's probably doing the same to the heart.
     
  6. yerrag

    yerrag Member

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    This makes sense but what I usually associate with cortisol being a hormone of stress is unsocial behavior. Perhaps depression is one unsocial behavior on a passive level, but on an active level I would see cortisol driving the unsocial expressions of unreasonable anger.
     
  7. Motif

    Motif Member

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    So... best ways to fix the cortisol issue?
     
  8. OP
    haidut

    haidut Member

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    The heart is actually relatively protected as it has high concentrations of testosterone (which blocks cortisol's effects). Peat explains this in one of his articles. Basically, since the heart is a vital muscle it be one of the last tissues to be broken down into sugar through gluconeogenesis when under stress. So, it accumulates high concentrations of testosterone to protect itself from cortisol and estrogen but eventually those supplies do get depleted and this is probably when heart attacks and/or cardiac arrest happen.
    This is another reason why it is good to eat organ meats like heart and liver - they have high concentrations of androgens, and sometimes progesterone as well.
     
  9. biffbelvin

    biffbelvin Member

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    This is really interesting.

    A friend of mine is on Sertraline (Lustral) but missed his prescription for a few weeks, due to a delay. Over that period he got a massive 'sweet tooth' (his own words) and on one evening he ate an entire packet of biscuits (cookies) in the space of 20 minutes.

    He's in his late 20's and works in retail, so the CUMS/CSD have a very clear root at least.
     
  10. Rafael Lao Wai

    Rafael Lao Wai Member

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    Thanks for the correction! That's good to know. Cardiovascular diseases would be more common if the heart was similar to arm muscles or leg muscles. I believe you mentioned beef tongue as a source of protective steroids as well.
     
  11. OP
    haidut

    haidut Member

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    In the animal models they call this "sucrose preference test". It is a test for anhedonia as a result of depression - i.e. depressed animals lose taste for sweet stuff, which they normally crave a LOT. So, if the sweet tooth is coming back then anhedonia may be abating and as such depression as well...
    SSRI drugs are pretty bad, and the fact that they lower desire for sweet is a good sign for their bad effects. Anything that causes anhedonia should be avoided.
     
  12. DaveFoster

    DaveFoster Member

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    I posted a relevant article on my blog a while back dealing with stress and hypersexuality. I'll just copy it here.

    Sex Addiction Caused by Stress and Trauma
    July 9, 2017

    Stress underlies addiction. The HPA axis controls the human response to stress, and HPA hyperactivation appears in behavioral disorders including hypersexuality:

    “A dysregulation of the hypothalamic pituitary adrenal (HPA) axis has been shown in psychiatric disorders…the diagnosis of hypersexual disorder was significantly associated DST non-suppression and higher plasma DST-ACTH even when adjusted for childhood trauma. The results suggest HPA axis dysregulation in male patients with hypersexual disorder.”​

    Researchers administered dexamethasone, which inhibits the stress-response, but hypersexual patients had a resistance to the drug.

    “Patients with hypersexual disorder were significantly more often DST non-suppressors and had significantly higher DST-ACTH levels compared to healthy volunteers.”​

    Those with hypersexuality suffer from childhood trauma and depression with the degree of trauma corresponding to HPA activation in adulthood:

    “The patients reported significantly more childhood trauma and depression symptoms compared to healthy volunteers. Childhood trauma questionnaire (CQT) scores showed a significant negative correlation with DST-ACTH whereas SCS and HD:CAS scores showed a negative correlation with baseline cortisol in patients.”​

    Sexual thoughts elevate testosterone in women:

    “Previous research suggests that sexual stimuli increase testosterone (T) in women and shows inconsistent effects of sexual arousal on cortisol (C), but effects of cognitive aspects of arousal, rather than behaviors or sensory stimuli, are unclear. The present study examined whether sexual thoughts affect T or C and whether hormonal contraceptive (HC) use moderated this effect, given mixed findings of HC use confounding hormone responses. Participants (79 women) provided a baseline saliva sample for radioimmunoassay. We created the Imagined Social Situation Exercise (ISSE) to test effects of imagining social interactions on hormones, and participants were assigned to the experimental (sexual) or one of three control (positive, neutral, stressful) conditions. Participants provided a second saliva sample 15 min post-activity. Results indicated that for women not using HCs, the sexual condition increased T compared to the stressful or positive conditions. In contrast, HC using women in the sexual condition had decreased T relative to the stressful condition and similar T to the positive condition. The effect was specific to T, as sexual thoughts did not change C. For participants in the sexual condition, higher baseline T predicted larger increases in sexual arousal but smaller increases in T, likely due to ceiling effects on T. Our results suggest that sexual thoughts change T but not C, baseline T levels and HC use may contribute to variation in the T response to sexual thoughts, and cognitive aspects of sexual arousal affect physiology.”​

    Sexual thoughts stimulate an increase in testosterone and cortisol:

    “Sexual stimuli increase testosterone (T) or cortisol (C) in males of a variety of species, including humans, and just thinking about sex increases T in women. We investigated whether sexual thoughts change T or C in men and whether hormone measures (baseline, post-activity, and changes) correlate with psychological sexual arousal. We used the Imagined Social Situation Exercise to assess how hormones respond to and correlate with sexual thoughts and arousal relative to three control conditions: neutral, stressful, and positive. A total of 99 men provided a baseline saliva sample, imagined and wrote about a sexual or control situation, and provided a second saliva sample 15 min later. Results indicated that, for participants in the sexual condition, higher baseline and post-activity C [cortisol] corresponded to larger increases in self- reported sexual and autonomic arousal. Although sexual thoughts increased sexual arousal, they did not change T or C compared to control conditions. Our results suggest that sexual thoughts are not sufficient to change T or C in men, but C [cortisol] may facilitate sexual arousal by directing energy towards a sexual situation."​

    Lowered cortisol increases individual resilience to stress and suppresses addictive behaviors.

    REFERENCES

    Chatzittofis, A., Arver, S., Öberg, K., Hallberg, J., Nordström, P., & Jokinen, J. (2016). HPA axis dysregulation in men with hypersexual disorder. Psychoneuroendocrinology, 63, 247–253. Redirecting Hypersexual disorder integrating pathophysiological aspects such as sexual desire deregulation, sexual addiction, impulsivity and compulsivity was suggested as a diagnosis for the DSM-5. However, little is known about the neurobiology behind this disorder. A dysregulation of the hypothalamic pituitary adrenal (HPA) axis has been shown in psychiatric disorders but has not been investigated in hypersexual disorder. The aim of this study was to investigate the function of the HPA axis in hypersexual disorder. The study includes 67 male patients with hypersexual disorder and 39 healthy male volunteers. Basal morning plasma levels of cortisol and ACTH were assessed and low dose (0.5mg) dexamethasone suppression test was performed with cortisol and ACTH measured post dexamethasone administration. Non-suppression status was defined with DST-cortisol levels ≥ 138 nmol/l. The Sexual Compulsive scale (SCS), Hypersexual disorder current assessment scale (HD:CAS), Montgomery-Åsberg Depression Scale-self rating (MADRS-S) and Childhood trauma questionnaire (CTQ), were used for assessing hypersexual behavior, depression severity and early life adversity. Patients with hypersexual disorder were significantly more often DST non-suppressors and had significantly higher DST-ACTH levels compared to healthy volunteers. The patients reported significantly more childhood trauma and depression symptoms compared to healthy volunteers. CTQ scores showed a significant negative correlation with DST-ACTH whereas SCS and HD:CAS scores showed a negative correlation with baseline cortisol in patients. The diagnosis of hypersexual disorder was significantly associated DST non-suppression and higher plasma DST-ACTH even when adjusted for childhood trauma. The results suggest HPA axis dysregulation in male patients with hypersexual disorder.

    Goldey, K. L., & van Anders, S. M. (2012). Sexual thoughts: links to testosterone and cortisol in men. Archives of Sexual Behavior, 41(6), 1461–1470. Sexual Thoughts: Links to Testosterone and Cortisol in Men Sexual stimuli increase testosterone (T) or cortisol (C) in males of a variety of species, including humans, and just thinking about sex increases T in women. We investigated whether sexual thoughts change T or C in men and whether hormone measures (baseline, post-activity, and changes) correlate with psychological sexual arousal. We used the Imagined Social Situation Exercise to assess how hormones respond to and correlate with sexual thoughts and arousal relative to three control conditions: neutral, stressful, and positive. A total of 99 men provided a baseline saliva sample, imagined and wrote about a sexual or control situation, and provided a second saliva sample 15 min later. Results indicated that, for participants in the sexual condition, higher baseline and post-activity C corresponded to larger increases in self- reported sexual and autonomic arousal. Although sexual thoughts increased sexual arousal, they did not change T or C compared to control conditions. Our results suggest that sexual thoughts are not sufficient to change T or C in men, but C may facilitate sexual arousal by directing energy towards a sexual situation.

    Goldey, K. L., & van Anders, S. M. (2011). Sexy thoughts: effects of sexual cognitions on testosterone, cortisol, and arousal in women. Hormones and Behavior, 59(5), 754–764. Redirecting Previous research suggests that sexual stimuli increase testosterone (T) in women and shows inconsistent effects of sexual arousal on cortisol (C), but effects of cognitive aspects of arousal, rather than behaviors or sensory stimuli, are unclear. The present study examined whether sexual thoughts affect T or C and whether hormonal contraceptive (HC) use moderated this effect, given mixed findings of HC use confounding hormone responses. Participants (79 women) provided a baseline saliva sample for radioimmunoassay. We created the Imagined Social Situation Exercise (ISSE) to test effects of imagining social interactions on hormones, and participants were assigned to the experimental (sexual) or one of three control (positive, neutral, stressful) conditions. Participants provided a second saliva sample 15 min post-activity. Results indicated that for women not using HCs, the sexual condition increased T compared to the stressful or positive conditions. In contrast, HC using women in the sexual condition had decreased T relative to the stressful condition and similar T to the positive condition. The effect was specific to T, as sexual thoughts did not change C. For participants in the sexual condition, higher baseline T predicted larger increases in sexual arousal but smaller increases in T, likely due to ceiling effects on T. Our results suggest that sexual thoughts change T but not C, baseline T levels and HC use may contribute to variation in the T response to sexual thoughts, and cognitive aspects of sexual arousal affect physiology.
     
  13. bluefish

    bluefish Member

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    If your rat has high cortisol... what’s a good idealabs remedy for that? I assume there are several...
     
  14. TheGoogler

    TheGoogler Member

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    @bluefish A consistent sleep schedule will do wonders for cortisol levels. So will minimizing screen time before sleep, regular exercise, meditation, and healthy diet. I urge you to consider optimizing your lifestyle and daily habits before considering the "quick fix" of supplements. There is far more reward in the path less traveled. I spent years trying to fix everything with supplements and finally came to the understanding that they should be last resort.
     
  15. Motif

    Motif Member

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    What about cold showers to lower cortisol?


    Or vibration plates? I was reading that they are helping with this
     
  16. bluefish

    bluefish Member

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    Yes I totally agree. I’ve actually taken most of these steps (with my rat) and it’s helped a lot. It’s really improved its life. I should go back to the drawing board and double check how I can improve each of these.
    Part of that has been including supplements... but yes, I think a year ago or so I finally committed to the basic fact: sleep, diet, exercise, mindset (meditation etc) need to be the corner stone for improving my life. ...
     
  17. bluefish

    bluefish Member

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    I’ve read some places cold showers can raise cortisol, and I’ve also read it lowers it.. I’m under the impression it lowers it... I regularly use breathwork and cold showers to lower mine. The best way I’ve been using is at a nearby Russian sauna , they have an amazing dry room (very hot) and cold pool (basically set to ‘freezing’) ... whenever I do a session there, the next day I feel amazing. Does it lower my cortisol? I’d assume so. Haven’t done any actual tests.
     
  18. tygertgr

    tygertgr Member

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  19. bluefish

    bluefish Member

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    So what are the best supps or herbs for lowering cort? I think mine is too high. I think due to life long issues it’s kinda stuck there.

    Any thoughts?
     
  20. tankasnowgod

    tankasnowgod Member

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    I noticed a profound improvement from adding 200 mg of Pregnenolone and aspirin (1 or 2 a day so far). I based the dose off of this-
    Pregnenolone Is The Most Potent Inhibitor Of The Stress Signal (CRH)

    I had been using some other anti-cortisol supplements (still am), but not seeing the improvement in mood and energy that I did from this combo. In some ways, it might depend on what is underlying the reason for elevated cortisol. I suspect inflammation is part of the reason in my case (due to some aches and pains), so think aspirin was a big key. It's been a little over a week so far, but this combination is working great so far.

    Of note, as per the "sleep schedule" mention earlier..... I think that poster is largely correct, but I currently wake really early during the week for my job. My guess is that as long as I am on this schedule, I will need the outward support. If I could sleep on a more normal schedule, this might not be necessary, or the dose might be a lot lower.
     
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