Stress and Cortisol -- long lasting effects

Original source: A perceived challenge can activate the mind/body system, resulting in increased alertness and stronger action, but chronic activation of this response leads to abnormal responses to stress characterized by 1) the inability of the body to return to baseline levels of catecholamines and cortisol, and 2) the inability of the body to activate the biochemical changes associated with a perceived challenge. When either of these response patterns develops due to continual activation of the stress response, then stress becomes debilitating.

Wikipedia: Cortisol

In normal release, cortisol (like other glucocorticoid agents) has widespread actions which help restore homeostasis after stress. (These normal endogenous functions are the basis for the physiological consequences of chronic stress - prolonged cortisol secretion.) * It acts as a physiological antagonist to insulin by promoting glycogenolysis (breakdown of glycogen), breakdown of lipids (lipolysis), and proteins, and mobilization of extrahepatic amino acids and ketone bodies. This leads to increased circulating glucose concentrations (in the blood). There is a decreased glycogen formation in the liver . [2] Prolonged cortisol secretion causes hyperglycemia. * It can weaken the activity of the immune system . Cortisol prevents proliferation of T-cells by rendering the interleukin-2 producer T-cells unresponsive to interleukin-1 (IL-1), and unable to produce the T-cell growth factor.[3] It reflects leukocyte redistribution to lymph nodes, bone marrow, and skin. Acute administration of corticosterone (the endogenous Type I and Type II receptor agonist), or RU28362 (a specific Type II receptor agonist), to adrenalectomized animals induced changes in leukocyte distribution. * It lowers bone formation thus favoring development of osteoporosis in the long term. Cortisol moves potassium into cells in exchange for an equal number of sodium ions.[4] This can cause a major problem with the hyperkalemia of metabolic shock from surgery. * It helps to create memories when exposure is short-term; this is the proposed mechanism for storage of flash bulb memories. However, long-term exposure to cortisol results in damage to cells in the hippocampus. This damage results in impaired learning. * It increases blood pressure by increasing the sensitivity of the vasculature to epinephrine and norepinephrine. In the absence of cortisol, widespread vasodilation occurs. * It inhibits the secretion of corticotropin-releasing hormone (CRH), resulting in feedback inhibition of ACTH secretion. Some researchers believe that this normal feedback system may break down when animals are exposed to chronic stress. * It increases the effectiveness of catecholamines. * It allows for the kidneys to produce hypotonic urine.

Effects of Therapeutic Interventions for Foster Children on Behavioral Problems, Caregiver Attachment, and Stress Regulatory Neural Systems

Abstract: Young children in foster care are exposed to high levels of stress. These experiences place foster children at risk for poor social, academic, and mental heath outcomes. The role of adverse events in stimulating neurobiological stress responses presumably plays a role in shaping neural systems that contribute to these problems. Systematic and developmentally well-timed interventions might have the potential to change developmental trajectories and promote resilience. Moreover, understanding how specific dimensions of early adversity affect underlying stress response systems and how alterations in these systems are related to later psychosocial outcomes might facilitate more precise and targeted interventions. Data are drawn from two ongoing randomized trials involving foster infants/toddlers and preschoolers. Consistent with prior animal models of early adversity, these studies have shown that early adversity—particularly neglect, younger age at first foster placement, and higher number of placements—is associated with altered hypothalamic-pituitary-adrenal (HPA) axis function. The interventions under investigation have produced evidence that it is possible to impact many areas that have been negatively affected by early stress, including HPA axis activity, behavior, and attachment to caregivers.

Low Cortisol, not high, after stress in childhood?

Development and Psychopathology (2001), 13: 515-538 Cambridge University Press doi:10.1017/S0954579401003066 Low cortisol and a flattening of expected daytime rhythm: Potential indices of risk in human development MEGAN R. GUNNAR a1 c1 and DELIA M. VAZQUEZ a2 a1 University of Minnesota a2 University of Michigan Abstract Since the work of Hans Selye, stress has been associated with increased activity of the limbic–hypothalamic– pituitary–adrenocortical (LHPA) axis. Recently, a number of studies in adults have shown that this neuroendocrine axis may be hyporesponsive in a number of stress-related states. Termed hypocortisolism, the paradoxical suppression of the LHPA axis under conditions of trauma and prolonged stress presently challenges basic concepts in stress research. Adverse conditions that produce elevated cortisol levels early in life are hypothesized to contribute to the development of hypocortisolism in adulthood. However, as reviewed in this paper, hypocortisolism also may be a common phenomenon early in human childhood. Although preliminary at this point, the ubiquity of these findings is striking. We argue that developmental studies are needed that help explicate the origins of low cortisol and to determine whether the development of hypocortisolism is, in fact, preceded by periods of frequent or chronic activation of the LHPA axis. We also argue that developmental researchers who incorporate measures of salivary cortisol into their studies of at-risk populations need to be aware of the hypocortisolism phenomenon. Lower than expected cortisol values should not necessarily be relegated to the file drawer because they contradict the central dogma that stress must be associated with elevations in cortisol. Lastly, we note that evidence of low cortisol under adverse early life conditions in humans adds to the importance of understanding the implications of hypocortisolism for health and development.

Maltreatment and neurotransmitters

Child maltreatment and the developing HPA axisstar, open Amanda R. Tarulloa and Megan R. GunnarCorresponding Author Contact Information, a, E-mail The Corresponding Author aInstitute of Child Development, 51 East River Road, University of Minnesota, Minneapolis, Minnesota, USA Received 12 May 2006; revised 6 June 2006; accepted 7 June 2006. Available online 28 July 2006. Abstract The developing HPA axis is under strong social regulation in infancy and early childhood and is vulnerable to perturbation in the absence of sensitive, responsive caregiving. Child maltreatment has complex, long-term influences both on basal cortisol levels and on HPA responsivity to pharmacological and psychological stressors, depending on current psychiatric status, current life adversity, age, and most likely, genetic factors. Among the more consistent findings, maltreated children with internalizing problems have elevated basal cortisol most often detected in early AM concentrations, whereas adults maltreated as children often exhibit low basal cortisol levels and elevated ACTH response to psychological stressors. To disentangle these complicated interactions, future research must take the above qualifiers into account, study the transition to puberty, explore the moderating role of candidate genes, and utilize animal models and pharmacological challenges, when ethical, to localize changes in the HPA axis. Post-institutionalized children may provide a model to separate early adverse care histories from current adversity. Keywords: Glucocorticoids; Hypothalamic–pituitary–adrenal axis; Stress; Maltreatment

Neurotransmitters and alcoholism (levels similar to our kids)

The HPA Axis The “Home” of Alcoholism in the Body and Mind Research has concluded that the “home” of alcoholism resides in the HPA (hypothalamus, pituitary, adrenal) axis of the neuroendocrine system. Now that we have the well-defined markers of addictive chemistry and we know where they live, scientists have developed extremely sophisticated tests which monitor the performance of this axis under various conditions by measuring dopamine, serotonin, GABA, glutamate, epinephrine (adrenaline), norepinephrine (noradrenalin), cortisol and DHEA which are the six big neurotransmitters and two key hormones which define either the health of the neuroendocrine system or its state and depth of illness. In Alcoholism: The Cause & The Cure you learn that addictive or addicted biochemistry is essentially the body's inability to adequately self-medicate with the natural, feel-good transmitters such as serotonin, GABA, dopamine and endorphins (as well as enkephalins) which predisposes an individual to “seek” relief in external ways such as alcohol. Addictive biochemistry is intricately associated with an upregulated (in excess) sympathetic nervous system where, due to low GABA, serotonin, and endorphins; excitatory neurotransmitters such as glutamate, norepinephrine and epinephrine are overexpressed which cause the many symptoms problem drinkers are known to self-medicate. It is also the bedrock of the progression of alcoholism in active drinkers because the longer one drinks, the more damage is done to the neuroendocrine system rendering it progressively unable to medicate the body naturally which intensifies symptoms which then causes one to drink more. To help you understand the root of this phenomenon I will go into a little more detail regarding genetic addictive biochemistry and active addiction and how they affect the HPA axis. The endocrine system is the network of glands in the body comprised of the hypothalamus, pituitary, pineal, adrenals, thyroid, parathyroid and the sex glands; ovaries and testes. These glands secrete hormones throughout the body to each and every organ via the blood which are received by their complimentary receptors. Hormones are “messengers” which carry messages coded by our DNA with the intention of keeping an organ regulated and healthy, essentially functioning as it should. A hormone's message will stimulate, suppress or maintain functional cell or tissue activity of the organ it is received by. The hypothalamus is the center piece of the endocrine system and is located in the middle of the base of the brain. The hypothalamus' ultimate purpose is to establish and maintain homeostasis; balance within the body. It regulates all the functions of the autonomic system of breathing, heart rate, etc… but also hunger, thirst, sexual drive, sleep urination and metabolism which includes blood sugar control. Although technically the hypothalamus is part of the endocrine system it is really central to both the endocrine and nervous system; in fact, it is in the hypothalamus that these two extremely complex systems of the body intersect. As the Master Accountant, the hypothalamus performs checks and balances and responds to chemical messages of deficient or excess by sending various hormones and neurotransmitters to “adjust” to the requirements of your internal and / or external environments to maintain status quo. The hypothalamus is able to do this because it houses receptor sites for both hormones from the endocrine system and neurotransmitters from the nervous system and it utilizes the information it receives from those sites to do its job of not only controlling the entire endocrine system, including having a profound influence on the liver, heart and kidneys, but establishing healthy brain chemistry and nervous system performance by correcting neurotransmitter imbalances by either slowing production of what is in excess, ingesting or degrading them faster, or in cases of deficiency, producing and releasing them as required. The door to addictive biochemistry opens when either the hypothalamus or one of the organs which serve the hypothalamus in accomplishing this job is injured, or if the nutrients required are not available. In any one of these conditions the entire system will fall off the “point zero” (homeostasis) that the HPA system tries to maintain, and the door for addictive biochemistry is opened. It is a well known fact that addictive biochemistry and full out alcoholism are associated with over expression of the sympathetic nervous system; low serotonin, GABA, dopamine, endorphins and enkephalins and it is in the hypothalamus where the delicate job of balancing this network of hormones and neurotransmitters to achieve physical and mental health is supposed to be done - whether it be directly from the hypothalamus or via the pituitary and adrenals under the control of the hypothalamus. The only difference between addictive biochemistry and full out alcoholism is that addictive biochemistry becomes aggravated, meaning that the deficient condition within the hypothalamus, pituitary or adrenals is made more profound by the damaging effects of alcohol toxicity and the medicating effects which, while drinking, overexpress serotonin, endorphins and dopamine which magnifies the negative impact of an already upregulated brain chemistry. The symptoms the problem drinker experiences intensify in direct relationship to the diminishing health of the neuroendocrine system which further encourages the person to drink more thus causing even more damage. This cycle progressively intensifies until intervention which discontinues and heals the damage is required to stop it. The pituitary gland is located below the hypothalamus and is directly connected to it via nerve and circulatory pathways. The hypothalamus regulates the function of the pituitary gland which in turn controls hormonal secretions of all other glands; however, specific to alcoholism we are concerned with the function of the adrenals and the secretion of cortisol which is under control of ACTH (adrenocorticotrophin) secreted by the pituitary, and epinephrine and norepinephrine which is also released by the adrenals due to a rise in CRH and/or signals from the sympathetic nervous system. In the case of cortisol release, when the hypothalamus registers low blood sugar it will send CRH (corticotrophin releasing hormone) to the pituitary which then releases ACTH which will cause cortisol to be secreted from the adrenals. This chain of events will also cause the release of epinephrine and to a lesser degree norepinephrine. Prolonged increased levels of epinephrine will block insulin receptors which leads to insulin resistance and lowered serotonin, endorphin, enkephalin and GABA levels which impairs HPA functions and increases compulsive / addictive behavior. The adrenals sit on top of the kidneys and are directly controlled by the pituitary gland. The adrenals are comprised of two sections; one is the medulla which is the inner core and the second is the adrenal cortex which is the outer layer. The medulla relates to the sympathetic nervous system and produces the catecholamines epinephrine and norepinephrine. The adrenal cortex produces sex hormones, aldosterone, and what we're most concerned with cortisol. The adrenals receive chemical messengers (hormones) from the pituitary and signal from the sympathetic nervous system which determines how much of its hormones it will release. However, if they are injured, diseased or fatigued they will not be able to keep up with the demands from the hypothalamus to maintain homeostasis and mild to severe mental disorders will surface as symptoms of compromised adrenal health. Although it is hard to imagine because they are docked on our kidneys, adrenal health is fundamental to our mental health. Proper levels of cortisol, epinephrine and norepinephrine are crucial to our mental well-being so concentrated focus needs to be applied to their health when healing addictive biochemistry and alcoholism. How They All Work Together I will use stress as an example of how the organs of the HPA work together and then we will take a look at how excessive alcohol use causes alcoholism and how to correct the metabolism so the addictive biochemistry and conditions for alcoholism are no longer present. During periods of acute stress special serotonin receptors on the hypothalamus are stimulated which cause the hypothalamus to produce CRF (corticotrophin release factor). The CRF is sent directly to the pituitary which causes ACTH to be sent to the adrenals which triggers release of cortisol. Cortisol is sent throughout the body on a number of different missions with the primary one to reduce the stress by stimulating serotonin (inhibitory neurotransmitter) in the amygdala which has an inhibitory effect on amygdala glutamate (excitatory neurotransmitter) which helps to calm the person down. The amygdala is directly connected to the hypothalamus and is a component of the limbic area of the brain where processing of emotions, fear, panic and long term memories occur. Many forms of depression, anxiety and panic disorders originate in the amygdala due to low serotonin and its inhibitory effects on the glutamate pathways of the amygdala. The HPA and Addictive / Addicted Biochemistry The genetic markers in the brain chemistry which spell alcoholism are the same for those that earned the condition through alcohol abuse; they are low endorphin, enkephalin, GABA, serotonin and dopamine expression which results in the over expression of the sympathetic nervous system; glutimate, epinephrine and norepinephrine. It doesn't necessarily have to be all of these; it could be just one or two that can engage the practice of self-medicating once a person, regardless of age, is exposed to a substance that helps balance their deficiencies. Albeit for a short time with known ramifications but it seems to be worth it because they will continue the habit until they find a way to stop the mild to severe symptoms they suffer through another means. The symptoms those with inherited capacity for addictive biochemistry are not as pronounced as the active drinker, however they are indeed debilitating and extremely mentally and physically uncomfortable. These symptoms can vary depending on the exact deficiencies of these neurotransmitters combined but they can include everything from depression, mental / physical fatigue and cravings for simple carbs to low self-esteem / confidence and low grade anxiety or restlessness. Alcohol can fix all of these in one fell swoop because it immediately raises all of the deficient neurotransmitters. The price to pay is high though, because on the other end comes the bottoming out of the already inherently low levels of neurotransmitters. Long-term drinking causes exaggerated over expression of the sympathetic nervous system due to overexpression of excitatory neurotransmitters glutamate, epinephrine, and norepinephrine; and underexpression of the inhibitory neurotransmitters; serotonin, GABA and dopamine, and the opioids endorphins and enkephalins during periods of sobriety which cause the “excitatory” symptoms I mentioned earlier which the individual is encouraged to self medicate. They will suffer their own combination of these now magnified symptoms due to the similar, now magnified neurotransmitter deficiencies. Due to the continual extreme demands on the adrenals, problem drinking invariably fatigues the adrenals and brings the problem drinker to a serious stress syndrome due depletion of cortisol, epinephrine and DHEA in concert with the depressive effects of low serotonin. Due to low cortisol / epinephrine, they will suffer from overexpression of norepinephrine which is known to cause irritability, anxiety, aggression, hypertension, and bipolar disorder. What happens within the body of those that have been abusing alcohol for a while and have damaged their neuroendocrine system is this: while the person is drinking, GABA, endorphins, dopamine and serotonin are overexpressed and literally emptied out from the CNS and hypothalamus which gives them the relaxation and medication for their symptoms they desire (which causes one to drink even more to achieve relief they found with far less alcohol early in their habit). This extreme depletion of inhibitory neurotransmitters leaves stores “empty” the next morning when they wake up which causes the overexpression of glutamate and the catecholamines. The symptoms of this condition are any of those I've mentioned including anxiety, restlessness, worry, short attention span, inability to focus, can't sit in one place for long, jitters, insomnia; basically most any feeling that is associated with being too “amped” up internally - this doesn't necessarily mean you feel like running a marathon; you don't. It means you are internally overexcited. Your endorphins and enkephalins were also over produced and emptied out so you won't have much of your natural pain killers available to mediate the condition you're in; ergo, soon you will have another drink. The internal scene with most people who rarely drink excessively is quite different; they have ample healthy stores of serotonin, dopamine, GABA, endorphin and enkephalin and they will immediately rise to the job of balancing the overexpressed glutamate and catecholamines. In the long-term drinker this is impossible because their body's ability to manufacture and replenish healthy levels of these neurotransmitters has been diminished from the damage of alcohol toxicity and the resulting malnutrition. The possible genetic handicap of not being able to naturally balance the autonomic sympathetic and parasympathetic nervous system by producing ample amounts of inhibitory neurotransmitters may also be involved which means there was a precondition of low levels of the natural feel-goods which will serve to accelerate the progression of alcohol abuse. Once the damage is established in the HPA by long-term drinking the cycle becomes deeply embedded in the person's biochemistry because this condition renders them entirely dependent on alcohol to achieve peace, relaxation and the natural euphoria of life because they can't feel good inside their own skin naturally anymore within a reasonable amount of time, and not without a bout of severe withdrawal which they are not inclined to endure. Inherited and acquired imbalanced, upregulated sympathetic neuroendocrine hormones and neurotransmitters are predominately caused by weakened or injured organs of the HPA caused by extreme blood sugar fluctuations over a considerable period and / or malnutrition. Alcohol metabolites such as acetaldehyde will also injure all of these organs in variable degrees making a considerable contribution to the addiction. A family history of unmet need for brain sugars due to a number of reasons such as famine or dietary restrictions due to location or climate which caused an excess of grains to be consumed over protein has been identified as contributing factors for weakened adrenals and injury to the hypothalamus and pituitary which can result in inheriting the predisposition to seek alcohol, other simple sugars and stimulants to self medicate. Another contributor to a genetic predisposition to addictive biochemistry is an early adoption of the industrialized food craze which began in the 40s and 50s which has now manifested in nearly 95% of what is at your supermarket being adulterated with sugars, hydrogenated fats, or foods so processed that there really isn't any food in the product anymore. These so called “foods” cause malnutrition and also damage the delicate workings of the HPA axis. Excessive dietary sugars, OTC, prescription and street drugs, malnutrition, disease and environmental toxins (especially acetaldehyde) can create a deficiency of neurotransmitters and imbalance or even damage the neuroendocrine system, creating an immediate requirement to replete and balance them before illness and possibly disease sets in. Alcoholism is extremely responsive to neurotransmitter repletion since it is their deficiencies and imbalance that is at the very root of alcohol addiction. In the Brain - a drink in a long time problem drinker (simplified) ? serotonin, GABA, endorphins and dopamine > hypothalamus produces ? CRF > pituitary produces ? ACTH > adrenals produce ? Cortisol. Sympathetic nervous system produces ? norepinephrine and epinephrine. 20 to 30 min. later, sharp drop in blood sugar, serotonin, endorphins and dopamine. Individual begins to feel “excitatory” symptoms. Has another drink, cycle begins again. Next day: Individual experiences symptoms of low levels of the feel-good neurotransmitters: serotonin, GABA, dopamine, endorphins, enkephalins and GABA. Concurrently, he/she will suffer symptoms of high cortisol (due to low blood sugar this time), glutamate, norepinephrine and epinephrine. The “tank” for the parasympathetic, feel-good neurotransmitters is emptied out and mental and physical capacities are diminished while the person suffers resulting symptoms. The individual begins to cultivate his/her habits around repletion of these neurotransmitters through the use of alcohol which progressively damages the person's ability to produce them and an addiction is born. The biochemistry of alcohol related symptoms exposed: Symptoms of long-term alcohol abuse directly related to HPA function: Stress Disorder There are possibly a hundred pathways for the various symptoms caused by alcohol toxicity and damage. I am provided a simplified one to demonstrate the very real fundamental message of this section: that alcohol toxicity and the results of its metabolism in the brain cause the psychological symptoms they suffer which triggers the survival mechanism to reduce pain and since they can't do it naturally, will seek it relief in alcohol. Due to alcohol toxicity damage and malnutrition, adrenal fatigue causes low cortisol output which leads to high norepinephrine levels (overexpressed). I've mentioned the debilitating symptoms of this condition earlier. The cause is because cortisol is required (along with SAMe) to produce epinephrine from norepinephrine. When this doesn't occur, norepinephrine is overexpressed while epinephrine and cortisol are diminished. Note here that cortisol is required in some areas of the brain to activate serotonin so when it is low it can also inhibit serotonin expression. This condition delivers one to the “alarm” stage of stress disorder due to the profound states of mind that can result from elevated norepinephrine including extreme anxiety, panic attacks, exaggerated fear (paranoia), insomnia, aggression, irritability, hypertension and even bipolar disorder. All of these conditions center on the deregulation of the HPA axis. How The 101 Program Corrects Addictive Biochemistry (simplified) Through the use of HPA axis testing, measuring the key neurotransmitters known to facilitate addictive biochemistry: dopamine, serotonin, GABA, glutamate, epinephrine, and norepinephrine. Cortisol and DHEA levels are also tested to establish the degree to which the adrenals are damaged so that an appropriate treatment for the adrenals can be developed. Once the neurotransmitter deficiencies are exposed, the practitioner can develop a personalized, targeted nutritional therapy (TNT) and aggressive nutriceutical protocol to bring the neuroendocrine system back into balance, optimizing the HPA axis and relieving the individual of the symptoms they self-medicate. Other contributing factors such as liver and GI damage are considered and addressed as well to provide the system with the best possible environment to heal and correct the “broken” metabolism.

Stress and brain development

Stress Brief periods of moderate, predictable stress are not problematic; in fact, they prepare the child to cope with the general world. The body's survival actually depends upon the ability to mount a response to stress (Shonkoff & Phillips, 2000). But prolonged, severe, or unpredictable stress-including abuse and neglect-during a child's early years is problematic. The brain's development can literally be altered by these experiences, resulting in negative impacts on the child's physical, cognitive, emotional, and social growth. Chronic stress sensitizes neural pathways and over-develops certain regions of the brain involved in anxiety and fear responses, and often results in the under-development of other neural pathways and other regions of the brain (Shore, 1997). Children who experience the stress of physical or sexual abuse will focus their brains' resources on survival and responding to threats in their environment. Children who experience the chronic stress of neglect-e.g., remaining hungry, cold, scared, or in pain-will also focus their brains' resources on survival. This chronic stimulation of the brain's fear response means that the regions of the brain involved in this response are frequently activated. When they are, other regions of the brain, such as those involved in complex thought, can not also be activated and are therefore not "available" to the child for learning (Shore, 1997). Because the brain ultimately controls all bodily functions, experiences that alter brain development also alter our bodies' responses. Studies have shown that "… the overwhelming stress of maltreatment experiences in childhood is associated with alterations of biological stress systems and with adverse influences on brain development" (DeBellis, et al., 1999). One example of the effects of early maltreatment on brain and body functions involves the chemical cortisol. Cortisol is a hormone that helps the body prepare to cope with stress through its effects on metabolism and the immune system (Hart, Gunnar & Cicchetti, 1995). Studies have shown that many infants and children who have been maltreated have abnormal secretions of cortisol, indicating that their bodies' responses to stress have been impaired (Hart, Gunnar & Cicchetti, 1995; Lott, 1998, citing Main, 1996). More research is needed to understand why this occurs and what effects this may have on the children's emotional and social development, but this information provides some evidence of altered brain activity in maltreated children. A key issue in understanding altered brain development in children who have been maltreated is that the way in which their brains develop is often a very adaptive response to their negative environment, but it is maladaptive in other environments (Hart, Gunnar & Cicchetii, 1996). If a child lives in a threatening, chaotic world, his brain will be hyper-alert for danger; his survival may depend on it. But if this environment persists, and the child's brain is focused on developing and strengthening its strategies for survival, other strategies may not develop as fully. If a child lives in a world that ignores him, if he is not provided with appropriate stimulation for growth, his brain will focus on survival from day to day and may not fully develop healthy cognitive and social skills (Ounce of Prevention Fund, 1996, citing Lieberman & Zeanah, 1995). The result may be a child who has great difficulty functioning when presented with a world of kindness, nurturing, and stimulation. It is an unfamiliar world to him; his brain has not developed the pathways and the memories to adapt to this new world.

Trauma and the Brain -- long term

Research Findings Research is continuing to reveal factors that may lead to PTSD. People who have been abused as children or who have had other previous traumatic experiences are more likely to develop the disorder. In addition, it used to be believed that people who tend to be emotionally numb after a trauma were showing a healthy response; but now some researchers suspect that people who experience this emotional distancing may be more prone to PTSD. Studies in animals and humans have focused on pinpointing the specific brain areas and circuits involved in anxiety and fear, which are important for understanding anxiety disorders such as PTSD. Fear, an emotion that evolved to deal with danger, causes an automatic, rapid protective response in many systems of the body. It has been found that the fear response is coordinated by a small structure deep inside the brain, called the amygdala. The amygdala, although relatively small, is a very complicated structure, and recent research suggests that different anxiety disorders may be associated with abnormal activation of the amygdala. People with PTSD tend to have abnormal levels of key hormones involved in response to stress. When people are in danger, they produce high levels of natural opiates, which can temporarily mask pain. Scientists have found that people with PTSD continue to produce those higher levels even after the danger has passed; this may lead to the blunted emotions associated with the condition. Some studies have shown that cortisol levels are lower than normal and epinephrine and norepinephrine are higher than normal. Norepinephrine is a neurotransmitter released during stress, and one of its functions is to activate the hippocampus, the brain structure involved with organizing and storing information for long-term memory. This action of norepinephrine is thought to be one reason why people generally can remember emotionally arousing events better than other situations. Under the extreme stress of trauma, norepinephrine may act longer or more intensely on the hippocampus, leading to the formation of abnormally strong memories that are then experienced as flashbacks or intrusions. Since cortisol normally limits norepinephrine activation, low cortisol levels may represent a significant risk factor for developing PTSD. Research to understand these neurotransmitter systems involved in memories of emotionally charged events may lead to the discovery of drugs or psychosocial interventions that, if given early, could block the development of PTSD symptoms.