Stress Lecture PDF

Stress and stress related disorders  What is Stress? Stress is a biological and psychological response experienced on encountering a threat that the individual feel that he doesn’t have the resources to deal with. Hence perceived as challenging to his capability. ▪ A stressor is the...

Stress and stress related disorders  What is Stress? Stress is a biological and psychological response experienced on encountering a threat that the individual feel that he doesn’t have the resources to deal with. Hence perceived as challenging to his capability. ▪ A stressor is the stimulus (or threat) that causes stress, e.g. exam, divorce, death of loved one, moving house, loss of job. ▪ It’s subjective, so something that is stressful for you may not be stressful for someone else. ▪ Stress can help anyone act quickly in an emergency or helping in meeting a deadline. ▪ The body responds to stress by producing hormones to help the person rise to the challenge. (stress hormones) ▪ But stress is meant to be temporary. The body should return to a natural state after the situation has passed. ▪ The prolonged stress put the body in a heightened state for a long period of time, making the physiological Reponses persist for longer than the body can handle. Over time, these can affect the physical and mental health, and behavior. Physiology of the Stress Response Hans Selye first described the stress response in the 1950s, and he emphasized its dual nature. In the short term, it produces adaptive changes that Stress help the animal respond to the stressor (e.g., mobilization of energy resources); in the long term, however, it produces changes that are maladaptive (e.g., enlarged adrenal glands). Adaptive Maladaptive Changes Changes  Physiology of the Stress Response The major feature of Selye’s landmark theory is its assertion that both physical and psychological stressors induce the same general stress response. This assertion has proven to be partly correct. There is good evidence that all kinds of common psychological stressors—such as losing a job, taking a final exam, or ending a relationship—act like physical stressors. However, Selye’s contention that there is only one stress response has proven to be a simplification. Stress responses are complex and varied, with the exact response depending on the stressor, its timing, the nature of the stressed person, and how the stressed person reacts to the stressor.  The physiology of stress Sympatho-adrenomedullary system Hypothalamic-pituitary-adrenocortical axis  SYMPATHETIC ADRENAL-MEDULLARY SYSTEM - ‘SAM system’ In response to a stressful stimulus or environment, the hypothalamus and the sympathetic nervous system stimulate the adrenal medulla to release epinephrine and norepinephrine. Together, these catecholamine hormones initiate a rapid activation of the sympathetic nervous system. Epinephrine affects glucose metabolism, causing the nutrients stored in muscles to become available to provide energy for strenuous exercise. Norepinephrine, the hormone also increases blood flow to the muscles by increasing the output of the heart. In doing so, it increases blood pressure, which, over the long term, contributes to cardiovascular disease. Besides serving as a stress hormone, norepinephrine is (as you know) secreted in the brain as a neurotransmitter. Some of the behavioral and physiological responses produced by aversive stimuli appear to be mediated by noradrenergic neurons  HYPOTHALAMIC PITUITARY ADRENAL AXIS The other stress-related hormone is cortisol, a steroid secreted by the adrenal cortex. Cortisol is called a glucocorticoid because it has profound effects on glucose metabolism. In addition, glucocorticoids help to break down protein and convert it to glucose, help to make fats available for energy, increase blood flow, and stimulate behavioral responsiveness, presumably by affecting the brain. Glucocorticoid secretion is controlled by neurons in the paraventricular nucleus of the hypothalamus (PVN), whose axons terminate in the median eminence, where the hypothalamic capillaries of the portal blood supply to the anterior pituitary gland are located. The neurons of the PVN secrete a peptide called corticotropin-releasing hormone (CRH), which stimulates the anterior pituitary gland to secrete adrenocorticotropic hormone (ACTH).  ACTH enters the general circulation and stimulates the adrenal cortex to secrete glucocorticoids. CRH (also called CRF, or corticotropin-releasing factor) is also secreted within the brain, where it serves as a neuromodulator/neurotransmitter, especially in regions of the limbic system that are involved in emotional responses, such as the periaqueductal gray matter, the locus coeruleus, and the central nucleus of the amygdala. The behavioral effects produced by an injection of CRH into the brain are similar to those produced by aversive situations. This indicates that some elements of the stress response appear to be produced by the release of CRH by neurons in the brain. A growing collection of research suggests that impaired regulation of the HPA axis is involved in many of the harmful effects of long-term stress. Allostasis is a term to describe the process of responding to stimuli and regaining and maintaining homeostasis. Allostatic load refers to the cumulative and collective wear and tear on body systems when there is too much stress response or when the stress response is not turned off. Allostatic load has been implicated in the negative health effects of prolonged or exaggerated stress response in stress and anxiety disorders.  Allostatic load Allostatic load is "the wear and tear on the body" which accumulates as an individual is exposed to repeated or chronic stress. The concept of allostatic load has been developed to refer to the physiological costs of chronic exposure to the physiological changes that result from repeated or chronic stress. This build up of allostatic load can be assessed by a number of indicators, including increasing weight and higher blood pressure  What is the Brain's Response to Stress??? Firstly, our body judges a situation and decides whether or not it is stressful. This decision is made based on - sensory input and processing (i.e. the things we see and hear in - stored memories (i.e. what happened the last time we were in the situation) a similar situation). If the situation is judged as being stressful, the hypothalamus is activated. Hypothalamus is in charge of the stress response. When a stress response is triggered, it sends signals to two other structures The pituitary gland The adrenal medulla. These lead to short term and long term Reponses to stress - Long term stress is regulated by the Hypothalamic Pituitary- - short term responses produced by the Fight or Flight Response Adrenal (HPA) system. via the Sympathomedullary Pathway.  Consequence of types of stress 1. Acute stress 2. Chronic stress Because it is short term, acute stress doesn't have enough time to do the extensive damage associated with long-term stress. The most common our stress response system was not designed to be symptoms are: constantly activated. This overuse may contribute to ▪ Emotional distress — some combination of anger or irritability, anxiety and the breakdown of many bodily systems.( ie blood depression, the three stress emotions. pressure and blood sugar stay in fight or flight mode). ▪ Muscular problems including tension headache, back pain, jaw pain and the chronic stress has been linked to heart disease, high muscular tensions (that lead to pulled muscles and tendon and ligament blood pressure, high cholesterol, type II diabetes, and problems). depression. ▪ Stomach, gut and bowel problems such as heartburn, flatulence, diarrhea, Especially ,for people at risk. For instance, if one has a constipation and irritable bowel syndrome. family history of heart disease, diabetes, high blood ▪ Transient overarousal leads to elevation in blood pressure, rapid heartbeat, pressure, or has unhealthy lifestyle habits, then sweaty palms, heart palpitations, dizziness, migraine headaches, cold hands or chronic stress can trigger these health problems. feet, shortness of breath and chest pain.  Adverse Effects of Stress - Healing The adverse effects of stress on healing were demonstrated in a study by Kiecolt-Glaser and colleagues (1995), who performed punch biopsy wounds in the participants’ forearms, a harmless procedure that is used often in medical research. The participants were people who were providing long-term care for relatives with Alzheimer’s disease— a situation that is known to cause stress—and control participants of the same approximate age and family income. The investigators found that wound healing took significantly longer in the caregivers (48.7 days versus 39.3 days).  Effects of Early Stressful Life Experiences Early life adversity in childhood can affect not only health in childhood (but also health across the lifespan into adulthood and old age. Some of this work grew out of the allostatic load view of stress, which argues that major, chronic, or recurrent stress dysregulates stress systems, which, over time, produce accumulating risk for disease. These early risks include low socioeconomic status, exposure to violence, living in poverty-stricken neighborhoods, and other community level stressors.  These difficulties include problems with emotion regulation and social skills. Children who grow up in harsh families do not learn how to recognize other people’s emotions and respond to them appropriately or regulate their own emotional responses to situations. As a result, they may overreact to mild stressors.  Children from risky families can develop heightened sympathetic reactivity to stress, exaggerated cortisol responses leading to health risks, and/or an immune profile marked by chronic inflammation. The more negative characteristics these adults reported from their childhood, the more vulnerable they were in adulthood to many disorders, including depression, lung disease, cancer, heart disease, and diabetes. Children from risky families often have poor health habits, some enhanced risk for disease may come from smoking, poor diet, and lack of exercise.  Are these effects reversible? At present it is unknown whether early life stress permanently programs stress systems or whether some of these effects are reversible. However, some factors, such as maternal nurturance in a high poverty environment, can be protective against the health risks usually found in high- stress areas.  Hippocampus the hippocampal formation plays a crucial role in learning and memory, and evidence suggests that one of the causes of memory loss that occurs with aging is degeneration of this brain structure. Research with animals has shown that long-term exposure to glucocorticoids destroys neurons located in the CA1 field of the hippocampal formation. The hormones appear to destroy the neurons by decreasing the entry of glucose and decreasing the reuptake of glutamate. Both of these effects make neurons more susceptible to potentially harmful events, such as decreased blood flow, which often occurs as a result of the aging process. The increased amounts of extracellular glutamate permit calcium to enter through NMDA receptors. (You will recall that the entry of excessive amounts of calcium can kill neurons.) Perhaps, then, the stressors to which people are subjected throughout their lives increase the likelihood of memory problems as they grow older.  Vicious Cycle of Stress The brain is responsible for turning on the stress reaction and for turning it off. If a stress response is not shut down, the body continues to mobilize energy at the cost of energy storage; proteins are used up, resulting in muscle wasting and fatigue; growth hormone is inhibited, and the body cannot grow; the gastrointestinal system remains shut down, reducing the intake and processing of nutrients to replace used resources; reproductive functions are inhibited; and the immune system is suppressed, increasing the possibility of infection or disease. Sapolsky (2005) argues that the hippocampus plays an important role in turning off the stress response. The hippocampus contains a high density of cortisol receptors, and its axons project to the hypothalamus. Cortisol levels are regulated by the hippocampus, but if levels remain elevated because a stress-inducing situation continues, cortisol eventually damages it. The damaged hippocampus is then unable to reduce the cortisol level.  Neurogenesis New neurons likely do replace old ones; however, their survival is not certain and can be affected by many types of experience. Stress is correlated with decreases in hippocampal-cell proliferation and survival, which comports with evidence that stress reduces mental efficiency and may especially impair some forms of memory. Stress has been shown to reduce dendritic branching in the hippocampus, to reduce adult neurogenesis in the hippocampus, to modify the structure of some hippocampal synapses, and to disrupt the performance of hippocampus-dependent tasks Perhaps even more interesting is the relation between chronic stress and depression and the finding that antidepressants that stimulate serotonin production (SSRIs such as fluoxetine) also increase neuron generation in the hippocampus. These observations suggest that the therapeutic activity of antidepressants may be related to their ability to stimulate neurogenesis, which in turn may alter mental activity. In Depression:  Psychoneuroimmunology Microorganisms of every description revel in the warm, damp, nutritive climate of your body. However, the body has four lines of defense to keep it from being overwhelmed. First is what has been termed the behavioral immune systems: Humans are motivated to avoid contact with individuals who are displaying symptoms of illness, and their bodies are primed to respond more aggressively to infection when they perceive signs of infection in others Second are a variety of surface barriers that keep the body from being overwhelmed. The major surface barrier is skin, but there are other mechanisms that protect from invasions through bodily openings (e.g., respiratory tract, eyes, and gastrointestinal tract). These mechanisms include coughing, sneezing, tears, mucous, and numerous chemical barriers. If microorganisms do manage to breach the surface barriers and enter the body, they are met by two additional lines of defense: the innate immune system and the adaptive immune system. Together, these two lines of defense constitute the immune system Stress and immune system High levels of cortisol tend to reduce the The immune system is one of the most ability to cope with vaccinations, and complex systems of the body. Its function heightened vulnerability to viral infection is to protect us from infection. Cortisol’s weakening effects on the immune The immune system derives from white blood cells (T-lymphocyte) that develop in the bone response related to it’s actions on T- marrow and in the thymus gland. lymphocyte. Chronic stress can lead to lowering the T-cells respond to cytokine molecules via a immunity. A lowered immune system means signaling pathway telling it to divide as there being more prone to colds and infections. is infection encountered in the body so start Stress increases the secretion of cortisol which fight and kill it. directly suppress the activity of the immune Cortisol blocks T-cells from proliferating by system. How?? preventing some T-cells from recognizing this cytokine signals. What is the explanation for the effects of stress and negative emotions on people’s susceptibility to infectious diseases??? The most important cause is that stress increases the secretion of cortisol which directly suppress the activity of the immune system. And as the secretion of cortisol is controlled by the CRH, hence the brain is responsible for the suppressing effect of this hormone on the immune system. Several studies have shown that stress increases the activity of neurons in the brain regions that have been shown to play role in emotional response including the central nucleus of amygdala and the hypothalamus. As, the neurons in the central nucleus of amygdala send axons to CRH- secreting neurons in the hypothalamus, consequently, increase the secretion of cortisol. Thus, the mechanism responsible for the negative emotional responses is also responsible for the stress response and the immunosuppression that accompanies both. PTSD  The risk for PTSD depends on both genetic and environmental factors. Kolassa et al. (2010) studied 424 survivors of the genocide in Rwanda. They found that the likelihood of developing PTSD increased with the number of traumatic events the person had experienced. They also found that people with a particular allele of the gene responsible for the production of COMT, the enzyme that destroys catecholamines present in the interstitial fluid, were more likely to develop PTSD. This allele (the Val158Met polymorphism) is associated with slower destruction of catecholamines, which supports the conclusion from other research that these neurotransmitters are associated with the deleterious effects of stress. An intriguing study by Gilbertson et al. (2002) suggests that at least part of the reduction in hippocampal volume seen in people with PTSD may predate the exposure to stress. In other words, a smaller hippocampus may be a predisposing factor in the acquisition of PTSD.  What role might the hippocampus play in a person’s susceptibility to developing PTSD? One possibility is that the hippocampus, which is involved in contextual learning, participates in recognition of the context in which a traumatic event occurs. The hippocampus then aids in distinguishing safe from dangerous contexts Consider a person who has been attacked by another person. The sight of other people who even slightly resemble the attacker or situations that even slightly resemble the one in which the attack occurred might then activate the amygdala and trigger an emotional response. However, a normally functioning hippocampus would detect the difference between the present context and the one associated with the attack and inhibit the activity of the amygdala PTSD and Amygdala Several studies have found evidence that the amygdala is responsible for emotional reactions in people with PTSD and that the prefrontal cortex plays a role in these reactions in people without PTSD by inhibiting the activity of the amygdala (Rauch et al., 2006). For example, a functional-imaging study by Shin et al. (2005) found that, when shown pictures of faces with fearful expressions, people with PTSD showed greater activation of the amygdala and smaller activation of the prefrontal cortex than did people without PTSD.  PTSD and Treatment Some treatment strategies focus on preventing PTSD following a traumatic event. In a recent review of preventative pharmacological therapies, Searcy et al. (2012) described studies that included administration of cortisol to patients immediately after experiencing trauma, with the goal of providing additional negative feedback to the HPA axis to reduce its activity. This counter- intuitive strategy appeared to be effective, and patients receiving cortisol were subsequently less likely to meet criteria for PTSD than patients receiving a placebo. In the same review, Searcy et al. (2012) also reported on the effectiveness of blocking catecholamine stress hormones (epinephrine or norepinephrine) and enhancing GABAergic activity using drug administration immediately following exposure to a traumatic event. Some researchers and clinicians tried administering propranolol, an antagonist at the beta adrenergic receptor, after a traumatic event (Vaiva et al., 2003) or prior to a therapy session intended to consolidate the memory of the traumatic event (Brunet et al., 2018) in an effort to interrupt the consolidation or reconsolidation of traumatic memories. Although the results of these studies suggest that this strategy is beneficial, this approach has been met with controversy over concerns about the disadvantages of preventing memory consolidation. Although the results are currently limited to a few studies, it appears that administrating drugs to manipulate stress response immediately after a traumatic event may be an effective treatment development for PTSD (Searcy et al., 2012).