Breaking the Silence: How Stress Affects Mental and Physical Health

Welcome everybody to this introduction to the HPA axis. I'm your host, Dr. Donnelly Snipes, and this is part of the PACER Integrative Behavioral Health Care series. In this video you're going to learn about the HPA axis in general, how it impacts all other major neurotransmitters and hormones and some of the symptoms of HPA axis dysfunction or imbalance. Now it's important to understand that this is designed to be a very high level overview of the HPA axis. There are going to be future videos that will go into each one of these hormones and chemicals and talk about how it impacts health and mood. But we're just going to start with the HPA axis, which is one of those overarching systems. The HPA axis is one of many systems in the body designed to ensure survival. The HPA axis is short for the hypothalamic pituitary adrenal axis. It works with the hypothalamic pituitary, thyroid and the hypothalamic pituitary gonadal axis. So the take home from that is our hypothalamus, our pituitary, our adrenal, our gonads and our thyroid are all very important in our functioning. And we'll talk about those other axes in a different video. The HPA axis is primarily thought of as being responsible for the fight orf flight reaction. It's the one that is kind of responsible for that threat response. It also helps regulate many homeostatic systems in the body. Home homeostatic systems are those systems that try to maintain balance. If you want to think of it like a bath, they try to keep the bath temperature just perfect. Not too hot, not too cold, kind of like a thermostat. So the HPA axis helps regulate homeostatic systems, including the cardiovascular system. When we're in fight or flee, guess what? The HPA axis helps increase heart rate, increase respiration when, when we are in a relaxation state. It helps slow respiration and heart rate. The metabolic system, the HPA axis helps regulate that when there's a stressor, when there's a threat. And this can include digestion. It doesn't have to be just a terrifying threat, it can just be a stressor on the body. The HPA axis is activated and will incur it speed up the metabolic system. When the HPA axis downregulates, then it helps down regulate the metabolic system. The same thing is true for the immune system, the reproductive system and the nervous system. The HPA axis integrates physical and Psychosocial influences in order to allow the organism, that's the person to adapt effectively to its environment, use resources and optimize survival. So the HPA axis takes in input from our, our nervous system and identifies if there are physical threats and anything that it is learned psychosocially about what is safe and what is beneficial and helps the brain make determinations about when there is a threat to the system and it needs to be activated. Stress causes the secretion of cortisol, your main stress hormone, adrenaline. We all know that adrenaline is a stimulant, norepinephrine, which is a neurochemical that helps us with energy as well as focus and attention. And glutamate, which is our main excitatory or energy neurochemical. So all that stuff kind of gets dumped. Cortisol causes the release of glucose or blood sugar for energy and acts as a steroid. Cortisol is a glucocorticoid. It's a steroid that acts as an anti inflammatory and suppresses the immune system. Why do we want this to happen? Well, the body is not devoting resources to repair right now. The, the body is devoting resources, all resources to fight or flee or deal with the threat. And that's what happens during, when the system is working well to an acute stressor, the inflammation is suppressed and the immune system is temporarily suppressed so the organism can fight or flee. Then when it's over, inflammation resumes and, and all of those inflammatory cytokines go scavenging throughout the body for any damage that was done where they might need to cause inflammation to enhance healing. Unfortunately, under conditions of hypocortisolism or glucocorticoid resistance, which happens when people are exposed to trauma. Sometimes this is not uncommon in people with ptsd, but also in people who are exposed to chronic stress over a long period of time. Time cortisol becomes unable to suppress the inflammation. So cortisol can ultimately become a problem and not be able to do its job. Glucocorticoid resistance, when tissues become resistant to cortisol, it means they don't respond to it. Why does that happen? Well, when tissues are exposed to cortisol too much, they develop this resistance to protect themselves. So it's a self preservatory sort of action of the body. However, it also doesn't help. So one of the things that we need to look at when we're evaluating people is the status of their HPA axis and whether they may be developing, you know, in the process of developing glucocorticoid resistance. One of the ways, or the main way to restore this balance so cortisol can do its job is to help the person not constantly have that HPA axis activated. We've got to heal the HPA axis and help it go back to turning on and off like it's supposed to. Adrenaline and norepinephrine, as I said, are, are secreted when the HPA axis is activated and they tell the pituitary gland to release endorphins. Now, we think about endorphins as feel good chemicals, and they kind of are. Think about when people are under extreme stress, what happens. A lot of times they don't feel pain in the moment. They're able to do things. They have strength that they never thought they'd have. Part of this is from the endorphins. Our body's goal in the acute phase of the HPA axis activation is to help us be able to tolerate pain and do whatever we need to do to escape the threat. So it totally makes sense. But when that system starts becoming dysfunctional, then the endorphins are another thing that quit getting released in the right way. So people start feeling more pain and they've got more inflammation. And we know that pain and inflammation are both associated with depression. Cortisol is your main stress hormone, and it generally, it peaks in the morning and gradually declines during the day. It helps regulate your circadian rhythms, control your blood sugar, regulate metabolism and inflammation. It assists with memory formation. It assists with control of fluid balance and salt balance and control of blood pressure. Now, you know, a lot of these things make sense in terms of blood sugar metabolism, inflammation and blood pressure. Those are all things that would be involved in fighting or fleeing. But memory formation is another one of those interesting things that gets impaired when cortisol is impaired, when people don't have enough cortisol or have too much, you know, either either end of the spectrum's bad, but it also helps regulate your circadian rhythms. And there is going to be another video that you'll watch on cortisol itself. So I'm not going to go deep into the details. What I want you to get from this is the fact that cortisol has its grimy little mitts in just about everything. So if people start developing cortisol resistance, glucocorticoid resistance, then a lot of things may start going wonky. Sleep, blood sugar, metabolism, autoimmune issues. You know, adrenaline is another one of those chemicals that's released. And we know adrenaline is a stimulant and it triggers the fight or flight reaction, increases blood pressure, respiration, and also helps with increasing blood sugar levels. We need blood sugar to be dumped so we have energy for that fight or flee. Thyroxin is a thyroid hormone. And during the fight orf flight response, during the HPA axis activation, the thyroid hormones help to regulate metabolism. They in during normal activation of the HPA axis, thyroid hormones go up. They help give us energy. Think about if we've talked to people with hypothyroid, they often have symptoms of depression. During normal activation of the HPA axis. We want people to have energy and not be depressed. So, you know, thyroid hormones are increased. That's good. Unfortunately, when there is chronic or extreme stress, the thyroid hormones tend to go down and people start developing hypothyroid symptoms. Why is this? Because all that excess cortisol circulating in the body as a result of the ongoing stress prevents the body from breaking T4, the first thyroid hormone, into usable T3. Adjusting, you know, if they go to their doctor and they get medication for their thyroid, okay, you know, that's one way to increase it. But that's not going to help the brain problem there. Ultimately we need to help the person reduce their cortisol levels so their body can effectively convert T4 to T3. Melatonin is another hormone that is involved sort of in this process. Now melatonin we always think of as the hormone that helps us fall asleep. Well, when the HPA axis is activated, melatonin's going to go down. You know, they have an inverse relationship. That's the first thing to recognize. So if the HPA axis is consistently activated because of chronic stress, guess what? People are not going to be able to get that restful sleep that they need. Melatonin is created from serotonin. If people don't have enough serotonin or if there is a breakdown in the serotonin system, they're not going to have be able to make the melatonin that they need. Melatonin is also interestingly an anti inflammatory and an antioxidant. So it can also help with reducing inflammation in the system. So when people start to get depressed and experience systemic inflammation, that's related to depression. One of the other things that we see is they often have low melatonin levels. Just an interesting point. Melatonin, as I said, is inversely related to cortisol. We are, we need to address what's causing the HPA axis dysfunction. The system will rebalance itself as soon as the machinery. As soon as the axes are working effectively. Other things that are impacted by the HPA axis disregulation include the gonadal hormones. Remember I said earlier, we have the hypothalamus, the pituitary gland, the adrenal gland, the thyroid gland, and the gonads. Estrogen and progesterone typically thought of as the female hormones, although, you know, men do have a certain amount of estrogen. Chronic stress and, and cortisol as a result of chronic stress, reduces estrogen most of the time and progesterone, resulting in what they call stress related amenorrhea. So women will also often stop menstruating because their hormones are out of balance. They also speculate that postpartum depression and postpartum autoimmune issues may be caused or contributed to by chronic stress. And it could be chronic emotional stress. You know, when the baby's new, you're not sleeping much and there's, you know, there may be a lot of stress with colic or, you know, whatever, that's a stressful time. But also the body is repairing after, after getting balanced, becoming homeostatic around growing a little organism inside you. Now it has to rebalance and reallocate all of its resources because it's no longer growing a little organism. So there's a lot of physical and psychological stress and maybe even emotional relationship stress during the postpartum period. That chronic stress can increase cortisol levels, which result in reduced estrogen and progesterone and depressive symptoms and sometimes anxiety. Estro estradiol is a type of estrogen that causes dysregulation of the HPA axis when it is not in the adequate balance. Estrad. Estradiol is one of those estrogens that is often used in birth control. So women who have difficulty with birth control are often, not always, it can be to progesterone or something else, but often having a reaction, an excessive reaction to the addition of the estradiol. Testosterone. Testosterone increases in response to cortisol and HPA axis activation. Makes sense. When we're stressed. We want that testosterone pumping through our system to give us energy and strength and make us feel more competitive. Unfortunately, like a lot of other things, under conditions of hypocortisolism or glucocorticoid resistance, if cortisol can't do its job, testosterone effectiveness decreases. When we're talking about hormones and neurotransmitters, there are multiple different ways that we can end up with insufficient or too much of them. We'll just talk about insufficient and you can, you know, extrapolate. Either the body doesn't have the building blocks to make it, or the system that makes it is broken down, or when the hormone is made and excreted, it doesn't stay in the synapse for long enough so the body can't make effective use of it. Or when the body secretes it into the synapse, it, it doesn't go through. You know, it may be absorbed, but it doesn't go downstream for some reason. So there are a lot of different ways and that's really not important for us. That's something that the physicians and the medical personnel can, can worry about. What we want to do is try to help the person make sure that they're getting the building blocks to make the hormones and neurotransmitters and they're doing the best that they can to make sure all of the systems are functioning properly in, that are designed to create and secrete these, these chemicals. Oxytocin is the third gonadal hormone hormone we'll talk about. And there's a positive correlation between oxytocin and cortisol, which I found to be fascinating, suggesting that when we're under stress, when we start feeling the stress, that part of our brain that is responsible for secreting oxytocin says hey, you need social support, you shouldn't do this alone. Now they don't know that for sure, obviously, but they have found that there is a positive correlation between oxytocin and cortisol. Oxytocin, remember, is our bonding hormone and it's responsible for pro social behaviors. So another hypothesis is that when we're under stress, our, our pro social behaviors kick in and help us protect ourselves and protect others. Dopamine is a neurotransmitter that is involved in just about everything. Dopamine increases in response to stress and excitement. It is what you would think of as your, I call it the perseveratory neurochemical or the motivation neurochemical. It makes you want to do it again. It makes you want to keep doing whatever you're doing. So it increases in response to stress and excitement in order to improve attention, vigilance and increase survival oriented learning. It helps you be more alert, it helps you be more motivated to survive, which also helps you be more aware of all the stimuli in your environment that could potentially be a threat. Well, that's fine. You know, we, that that's a good thing. But it's important to recognize that we need dopamine for a lot of other things. So if the brain starts becoming resistant to the dopamine, then the person may start experiencing energy and mood issues. They found that in depression, for example, for some people, they benefit from a dopamine reuptake inhibitor, others benefit from serotonin reuptake inhibitors, and yet others benefit from norepineph epinephrine reuptake inhibitors. So the cause, the, the neurochemical cause of people's depression or the area of the system that breaks down may be different for different people. And that's important to know as well. Acetylcholine is another neurotransmitter involved in functioning, and it's positively correlated with HPA axis activation in general. In general, as HPA axis goes up, acetylcholine goes up. But interestingly, also so does depression. The symptoms of depression, the anhedonia and things like that do seem to go up as, as acetylcholine goes up. And they found in some studies that serotonin seems to go down. So there's an inverse relationship between acetylcholine and serotonin. The thing we really want to know here again is that there can be neurochemical causes. We are not going to be helping people target any particular neurotransmitter. That's between them and their doctor. But we do want to help them, you know, evaluate their, their diet, make sure that they are communicating with their dietitian about what they're eating to make sure they're getting the building blocks that they need and, and not too much of some of them. Some things, like eggs, are high in choline, and some people are especially sensitive to that. Norepinephrine is needed to synthesize and release melatonin by the pineal gland. When cortisol levels are high, this process just doesn't take place. The norepinephrine is being used for something else. The body is not focused on making melatonin. And glutamate, remember, is your main excitatory neurochemical. But glutamate serves a dual purpose. It's your main excitatory neurochemical, but it can be broken down to make gaba, which is your main calming chemical. When people are using a lot of glutamate, when people are number one, a bunch of glutamate in the brain makes it run sort of too hot, if you want to think about it that way, and it actually becomes what they call excitotoxic, and starts killing brain cells. So that's not a good thing. We do want to help people regulate their glutamate levels. But the brain can also start having problems with glutamate accessibility. And there can be a breakdown in that system. And when glutamate's not available, it can't be broken down to make gaba. So some people may have difficulty with anxiety because they've got too much glutamate or because they don't have enough glutamate that to be broken down into gaba. So they don't have enough gaba. These are things that we will explore and hypothesize about. Currently, there is no cost effective, widely accessible way in humans to measure neurotransmitter levels in the brain. Neurotransmitters exist throughout the body. And so you can do a urine test and find out what your level of serotonin is, but you don't know how much of that serotonin is in your gut and how much of it is your in your brain. And you don't know whether it's a problem with lack of enough serotonin or a breakdown in the communication system, in the serotonin system. Which brings us to serotonin. Serotonin is the one that most of us think of in terms of an antidepressant. But as I said, dopamine and norepinephrine are also implicated in, in depression, as well as cortisol. Cortisol prevents a lot of other chemicals from doing what they need to do and can contribute to depression. Serotonin balance is altered in response to the HPA axis. Now, when you learn, when you watch the video on serotonin, you'll learn that there are multiple different types of serotonin receptors. The two main ones that you want to know about are 5ht1 and 5ht2. 5ht1 goes down when the HPA axis is activated. That's the one that helps you feel calm and helps with anxiety and is related somewhat to depression. 5 HT2 is more excitatory in nature. When it goes up, your respiration and heart rate tend to go up more. Serotonin, as I said earlier, is broken down into melatonin or when it's time for bed, when the HPA axis is activated, the body says it is not time to rest and digest. It is not time to be content. It is time to fight or flee. So serotonin levels go down. When the HPA axis is up, you know our calming serotonin levels. And that also means that, that 5ht1 can't be broken down into melatonin. High levels of cortisol also prevent the release of melatonin. So even if you've got enough serotonin and it's made and whatever, if you're still stressed out, as I mentioned when we were talking about melatonin earlier, if you're still stressed out, cortisol and the HPA axis say there's still a threat. It is not safe to be asleep and relaxed. So, you know, we're not going to release the melatonin. Remember, melatonin helps with sleep, but also helps with pain and inflammation as well. So people may start feeling more pain, experiencing more inflammation and more mood symptoms. What does it look like when the HPA axis is not functioning right? Well, there is direct evidence to implicate HPA axis dysfunction in cardiovascular disease, including high blood pressure in pain and inflammation, and autoimmune issues. Remember, cortisol is a steroid and assists with inflammation suppression when the system is working well. But when it's not working well, cortisol is not able to make exert its effects and that can also, that can lead to autoimmune issues. HPA axis dysfunction can result in sleep problems, including insomnia. Because when cortisol is out of whack, cortisol spikes in the morning and decreases throughout the day. When it's at its lowest point, then serotonin can start being create, not broken down to make melatonin. But if cortisol stays high or never rises, then it's going to affect the availability of all those other hormones and chemicals. Fatigue is implicated. When we can't get good sleep, we're often going to be fatigued. When that HPA axis is hypervigilant, we are likely spending a lot of energy. We've got a lot of often muscle tension that also can contribute to fatigue, reduced libido. The body says if there's a threat, it's not time to procreate. That's the short version, pcos, or polycystic ovarian syndrome. Remember, we talked about how cortisol and the HPA axis, when they're activated, can alter levels of estrogen, progesterone and testosterone. People with PCOS tend to have too much testosterone. And in their system, cancer has been directly tied to HPA axis dysfunction, which is one of the reasons one of the main preventative strategies, along with diet and exercise, is stress management as a preventative step towards cancer. But it's also important, when somebody has cancer, that HPA axis is going to be, you know, going strong to help them minimize any additional stresses on it so they can do the best they can to make sure that they don't develop glute, glucocorticoid resistance, that their immune system is as strong as it possibly can be in the face of the cancer. Diabetes tends to get a lot more difficult to control when the HPA axis is not functioning well because it has such a direct effect on blood sugar. Affectively, people with post traumatic stress often develop HPA axis dysfunction because of their hypervigilance. Now, if they've, you know, processed their post traumatic stress and it's in remission, that's not what we're talking about. We're talking about people who are still experiencing hypervigilance, night terrors, irritability, all of the fight or flee sort of symptoms of ptsd. HPA axis dysfunction is related to all types of depression, postpartum depression, persistent depressive disorder, bipolar depression, and major depressive disorder. Depression is associated with inflammation as well as imbalances in some of those other chemicals. If you're stressed out all the time and your 5ht1 levels are low, your serotonin levels are low, guess what? That's probably going to contribute to some mood symptoms. It also contributes to anxiety and chronic stress. We, when we are on fight ORF flight mode most of the time or, and or live living, quote, living on caffeine, which is a stimulant, and that will also trigger the HPA axis. People can have feelings of anxiety. When you've got glutamate and adrenaline and cortisol coursing through your system, you are likely going to feel symptoms of irritability and anxiety. And a lot of times people use emotional reasoning and misconstrue what's going on with them physically as a threat in the environment. Not always, but sometimes and cognitively. HPA axis dysfunction has not so long ago been tied to cognitive impairment. When it's time to fight or flee, it's not time to focus and learn, but also with the development of dementia. So it's important because of the high levels of glutamate and the glucocorticoid resistance and, you know, dysfunction that results when there's too much cortisol in the system. One step to help people prevent or cope with dementia would be to address that HPA axis to make sure that it is not contributing to the problem. When we're treating people with HPA axis dysfunction, it's, you know, a complex interaction, but we can start with the basics. Consider the source of the stress. And yes, most of you who are watching are behavioral health professionals, social workers, counselors, marriage and family therapists, maybe pastors. However, it's still important to understand the sources of the stress so we can make appropriate referrals. Physically do, are they getting adequate nutrition? Do they have the building blocks? Or their body can make all of those neurochemicals, if not referral to a dietitian or to their primary care Sleep, Are they getting good quality, adequate sleep, seven and a half to 10 hours a night, preferably without having to, without, you know, drinking in order to fall asleep? You know, we need to make sure it's quality sleep. If not, we can work with them on sleep hygiene. They may need to be referred out for, for a sleep study if they, if there's a possibility they have sleep apnea. Sleep apnea triggers the HPA axis and when you've got sleep apnea all night long, then that contributes to the development of glucocorticoid resistance and worsens diabetes and all kinds of other things. So we do need to make sure that we're ruling out sleep apnea, helping people with their sleep hygiene, general health behaviors. We want to make sure that they've had a physical, if they're presenting with symptoms now, preferably a physical within the last three months that has, where the doctor has drawn blood and assessed their vitamin D levels, has assessed their hormone levels, has assessed their thyroid levels to make sure that there's no underlying physiological cause for the imbalance. For the HPA axis to be active and pain, some pain will need to be addressed through the physician. And generally you're going to want to work in concert with the physician on this. But there are also all kinds of non pharmacological pain techniques, including ice and heat and guided imagery and meditation and other things that can be used to help people deal with chronic non cancerous pain. Affectively, we want to assess, you know, the source of the dysphoria and that kind of encompasses all of those unpleasant emotions, the anger, the anxiety, the depression. We want to look at the sources of stress and, you know, those can be targets for our treatment plan, but we also want to look at the sources of the euphoria. It's important not just to take away the bad, well, not take away the bad feelings, help people cope with the bad feelings, but also help them add in happy feelings, add in positive feelings. What are they doing that may help them feel a little bit better? Cognitively, we want to examine unhelpful thought patterns and problem solving challenges. That they may be experiencing that's contributing to frustration and anger and HPA axis activation. We also want to look at neurological differences. If you are working with a person who has autism or schizophrenia, it's important to examine and discuss with them how they experience the world differently than other people. What we may not see as a problem, what we may not be overwhelmed my by may be completely overwhelming or traumatic to them. So it's important to assess how people perceive the world, how they think about the world, and what they think of as threatening environmentally. We want to look both for sources of stress in the environment, but also for sources of relaxation and happiness in the realm of smell, sounds and light. Smells, you know, the noxious smells, or if people have bad allergies, that can be a problem they may need to address that. You know, bad allergies may keep people from sleeping well, you know, whatever sounds that keep people from sleeping or even just constant lowgrade noise may contrib well. We know it contributes to HPA axis activation and is a source of chronic stress. Light that is glaring light that is what I just call obnoxious or lights that flicker can be very stressful to the body. So helping them assess their environment for anything that may be adding to their stress or discomfort, but also to modify their environment to add things that may make it more comforting, feel safer and more pleasant. And then relationships, you know, we want to look at their relationships and in what ways relationships are, are buffering against stress and what ways relationships are contributing to stress. When we, once we identify the sources of the stress, the sources of the HPA axis activation, then we can start helping the person try to prioritize and take steps towards addressing each one of them to help them move towards that. Health, happiness and homeostasis, I guess, is what we'll call it. The HPA axis is crucial for survival in the face of distress. Dysfunction of the HPA axis is involved in a variety of physical, affective and cognitive issues. And when people are unwell, unhappy, or, and, or having difficulty concentrating, it takes a toll on their relationships and their environment. So it's all interwoven. The breakdown in the system will likely continue to get worse even if you do find ways to temporarily mask it. So it's important to figure out, you know, let's trace it back. You've got depression, you know, what may be associated with that. Are we ruling out what, Are we ruling out all the potential causes of dysfunction of the HPA axis until we find what's causing, what's actually causing the dysfunction thank you for being with me.