Fight-or-Flight Response and Depression



Pert, Candace B. (2010-05-08). Molecules of Emotion: The Science Behind Mind-Body Medicine (p. 268). Scribner. Kindle Edition. 




“My sister has been on Prozac for years.” Kate blurts out.“I don’t think we know enough about the stuff, and I’ve told her so. But she’s convinced that the drug is the answer to her problems. And she refuses to deal with any of the underlying issues that I believe to be at the heart of her problems.”


“She is convinced that if only her husband hadn’t left her, everything would be okay— she can’t seem to get past that,” Kate interjects.


“And right you are to be concerned,” I begin, delighting in the chance to take my listeners a little deeper into the science, “Just recently, researchers at the National Institutes of Health have found a link between depression and traumas experienced in early childhood. Studies have shown that abused, neglected, or otherwise unnurtured infants and children are more likely to be depressed as adults, and now we have a way to understand the link between the experience and the biology. It all relates to something called the hypothalamic-pituitary-adrenal axis.”


Here is the schematic representation of the section "Fight-or-Flight Response Mechanism"..


How does the response end? How is this regulated?

Short answer: High cortisol feeds back and shuts down ACTH and CRH production (two feedback loops)


Excerpt from Wikipedia:

"After enough cortisol has been secreted to best restore homeostasis and the body’s stressor is no longer present or the threat is no longer perceived, the heightened levels of cortisol in the body’s blood stream eventually circulate to the pituitary gland and hypothalamus to which cortisol can bind and inhibit, essentially turning off the HPA-axis’ stress-response cascade via feedback inhibition."


"It is when the body’s HPA-axis cannot overcome a challenge and/or is chronically exposed to a threat that this system becomes overtaxed and can be harmful to the body and brain. A second major effect of cortisol is to suppress the body’s immune system during a stressful situation, again, for the purpose of redistributing metabolic resources primarily to fight-or-flight organs. While not a major risk to the body if only for a short period of time, if under chronic stress, the body becomes exceptionally vulnerable to immune system attacks."





Pert, Candace B. (2010-05-08). Molecules of Emotion: The Science Behind Mind-Body Medicine (p. 268). Scribner. Kindle Edition. 


(…) A group of monkey babies was raised by a fake monkey mother, a wire-and-cloth structure with milk bottles instead of breasts. The babies were fed but not touched, cuddled, or held. They soon had all the signs of trauma and depression”.


CRH (synonym: CRF) levels were increased.


“But they were cured— the stress symptoms reversed— when researchers brought in what they called a ‘monkey hug therapist,’ an older monkey who constantly hugged and cuddled the stressed-out baby monkeys. So what was going on? The hugging broke the feedback loop, sending the message ‘No more steroids needed,’ damage over and done with! The chronically elevated CRF levels came down.”


“So when we see those bumper stickers ‘Hugs Not Drugs,’ we should take them more seriously!” Dee points out. We all laugh at the realization that the science I’ve been laboring at such length to explain is obvious enough to have become popular bumper-sticker wisdom.



“Of course, I’m not suggesting that hugs alone can cure all our major ills.” I say. “The prescription drugs do serve a purpose, and I recognize that they save people’s lives. It I have a bad infection, I’m going to use an antibiotic. If I have a serious clinical depression, I will take an antidepressant. But from my research with the endorphins. I know the power of touch to stimulate and regulate our natural chemicals, the ones that are tailored to act at precisely the right times in exactly the appropriate dosages to maximize our feelings of health and well-being.”



“So that’s why people feel better when they get a good massage or other kinds of hands-on healing,” Dee joins in.


I first came in contact with somatic-emotional release approaches, also called “body psychotherapy.” at Esalen in California, when I gave a talk there in the early eighties. The Greeks and Romans had their baths, their spas, their temples of healing at places like Epidaurus, and we have Esalen, where beautiful, natural springs come from deep within the earth to fill the pools perched high on a bluff over the Pacific at Big Sur. Which I spent some time in the baths of Esalen, I met many massage therapists, chiropractors, and theorists who saw my research as a confirmation of what they were seeing in their practices. I was very impressed by their power to simultaneously access the emotions through various kinds of body work while enlisting the power of the mind through talk, thus creating what seemed like a loop of healing.


Pert, Candace B. (2010-05-08). Molecules of Emotion: The Science Behind Mind-Body Medicine (p. 274). Scribner. Kindle Edition.


My research has shown me that when emotions are expressed— which is to say that the biochemicals that are the substrate of emotion are flowing freely— all systems are united and made whole. When emotions are repressed, denied, not allowed to be whatever they may be, our network pathways get blocked, stopping the flow of the vital feel-good, unifying chemicals that run both our biology and our behavior. This, I believe, is the state of unhealed feeling we want so desperately to escape from.



On the Mechanism


But another thing that the adrenal glands do, which is what happens when ACTH hits them, is that they begin to make steroids. These are not the steroids associated with sex and the reproductive system, however. “The steroid they make is corticosterone (note: cortisol), a substance that is necessary for healing and damage control when an injury has occurred You’ve all probably applied cortisone cream for a skin rash or had a cortisone shot to treat poison ivy or oak.


“Now, here comes the connection to clinical depression. Ever since studies done thirty years ago, we’ve known that stress increases with increased steroid production. Depressed people typically have high levels of these stress steroids. In fact, depressed people are in a chronic state of ACTH activation because of a disrupted feedback loop that fails to signal when there are sufficient levels of steroid in the blood. So the CRF-ACTH axis just keeps pumping out more and more steroids. Autopsies almost always show a tenfold higher level of CRF in the cerebrospinal fluid of those who killed themselves compared to those who died from other causes.”


“Sounds like this CRF is the depression peptide.” Kate says.

“Assuming that a given peptide has a specific tone, that is.” she continues, referring to some of the more speculative excursions of my lecture.


“It sure looks that way. We could say that CRF is the peptide of negative expectations, since it may have been stimulated by negative experiences in childhood. There are animal studies, for example, showing that monkey babies deprived of maternal nurturing, neglected or abused, in effect, have high levels of CRF and so have high steroid levels. Remember, it’s a feedback loop that is out of control. Depressed people are stuck in a disruptive feedback loop that resists any kind of drug therapy that aims at suppression of the steroids. Eventually, there is so much CRF in the system that fluctuations of other peptides throughout the organism are curtailed, leaving ever lower possibilities in the range of behavior.


In baby monkeys, this takes the form of failure to groom or repetitive behaviors that don’t seem to have any purpose. In humans, the result can be extremely limited patterns of behavior and response, which eventually drive people into an emotional black hole.”


“My sister is convinced that if only her husband hadn’t left her, everything would be okay— she can’t seem to get past that,” Kate interjects. “Yes, and the reason we can get stuck like this is because these feelings get retained in the memory— not just in the brain, but all the way down to the cellular level. This is how it works: As CRF levels increase in highly stressed infants and children, the receptors for CRF become desensitized, shrinking in size and decreasing in number. These changes happen when receptors are flooded with drug, whether it’s drug your body produces naturally or a drug you buy at a pharmacy. The memory of the trauma is stored by these and other changes at the level of the neuropeptide receptor, some occurring deep in the interior of the cell at the very roots of the receptor. This is taking place bodywide. Although such changes can be reversed and need not be permanent, this takes time.”