Stress Let’s take the example of stress again. This time mom doesn’t have to be stressed out during pregnancy, but rather it’s the chronic stress and strain, the daily wear and tear that women experience that cause them to have higher stress reactivity. How does this happen? What happens when you are stressed? What happens when you see a saber tooth tiger? You run! Your body activates the fight-or-flight response -- the hypothalamic-pituitary-adrenal system and the sympatho-adrenal-medullary system -- to put out more stress hormones -- CRH and ACTH and cortisol and catecholamines -- to help you run faster. Photo: http://www.lam.mus.ca.us/cats/encyclo/smilodon/

Stress: The Importance of Allostasis The term came into being in the 1980’s as a newer more appreciative way to view the body’s rapid and efficient methods of dealing with stress. Allostasis refers to the body’s ability to maintain stability amidst change. M Lu, N Halfon

Allostasis: Maintain Stability through Change But what happens after you got away? Your heart rate slows down, your blood pressure comes down, and you body calms down. The amazing thing about the human body is that it is self-regulating; it knows to shut itself off once the stressor has been removed. This is called allostasis – maintaining stability through change. McEwen BS. Protective and damaging effects of stress mediators. N Eng J Med. 1998;338:171-9.

Allostasis: Wear and Tear There are, however, situations that ignite stress response in which neither fight nor flight is an option….the response cannot help us toward resolution. Then, deprived of its natural result, the system designed to protect us begins to cause wear and tear  illness and vulnerability.

ALLOSTASIS TO ALLOSTATIC LOAD Four Scenarios McEwen B. New England J. Med. 1998

Stress and Biology: Allostatic loading Unremitting chronic stress, or severe trauma, particularly at windows of vulnerability and opportunity in human development. Inability to adjust. Not hearing the “all-clear” signal Feedback loops impaired. Practical leadership action: 1. Foster conditions to prevent stress and severe trauma. 2. Strengthen capacity to deal with stress. 3. Promote healing from stress and trauma.

What we often mean by “stress” is being “stressed out”! Feeling overwhelmed, out of control, exhausted, anxious, frustrated, angry What happens to us? Sleep deprivation Eating too much of wrong things, alcohol excess, smoking, etc. Neglecting regular, moderate exercise All of these contribute to allostatic load Psychosocial stress is a major factor

Levels of stressful experiences: Their causes, consequences and why we experience them! Positive Stress - A personal challenge that has a satisfying outcome Result: Sense of mastery and control -HEALTHY BRAIN ARCHITECTURE -good self esteem, judgment and impulse control Tolerable Stress Adverse life events buffered by supportive relationships Result: Coping and recovery HEALTHY BRAIN ARCHITECTURE Toxic Stress Unbuffered adverse events of greater duration and magnitude Result: Poor coping and compromised recovery Result: Increased life-long risk for physical and mental disorders COMPROMISED BRAIN ARCHITECTURE Dysregulated physiological systems

HPA Axis Hypothalamic-pituitary-adrenal axis Initiated in the hypothalamus gland, it is the cornerstone of allostasis. Impaired HPA axis function from toxic stress leads to chronic high levels of cortisol. Prolonged high levels of cortisol suppress immune function, increase inflammation, and may lead to LBW,preterm birth, diabetes, c-v disease, etc. Toxic stress may thus result in a hyper-reactive, dysregulated HPA axis. Two possible mechanisms: Cumulative “wear and tear” (weathering) throughout the life cycle and fetal or childhood programming.

Social environment and health Central Role of the Brain MacArthur Foundation Research Network on Socioeconomic Status and Health Behavioral responses (“lifestyle”) as well as stressful experiences McEwen B. New England J. Med. 1998

Prenatal Programming of the Hypothalamic-Pituitary-Adrenal Axis More importantly, the hippocampus and the amygdala regulates the hypothalamic-pituitary-adrenal axis, which mediates our fight or flight response. Now I want you to think of the hippocampus as a brake pedal on the hypothalamic-pituitary-adrenal axis; it brakes the HPA axis. And I want you to think of amygdala as the accelerator pedal; it accentuates the action of the HPA axis. Prenatal stress increases the release of glucocorticoids from fetal adrenal glands, which can downregulate glucocorticoid receptors in the hippocampus, and at the same time upregulate glucocorticoid receptors in the amygdala. So you are making the brake pedal less sensitive to negative feedback, and making the accelerator pedal more sensitive to positive feedback. What do you get? You end up with a fetus with a hyper-reactive HPA axis. Welberg LAM, Seckl JR. Prenatal stress, glucocorticoids and the programming of the brain. J Neuroendocrinol 2001;13:113-28.

Many targets for cortisol Stress, allostasis and allostatic load AVP CRH Cortisol ACTH Acute - enhances immune, Memory, energy replenishment, Cardiovascular function Chronic - suppresses immune, Memory, promotes bone Mineral loss, muscle wasting; Metabolic syndrome

Mediators of stress and adaptation NETWORK OF ALLOSTASIS CNS function Metabolism Immune function Cardiovascular function Dysregulation by Biphasic and non-linear -unhealthy lifestyle, poor sleep, toxic chemicals -feed into network of allostasis (eg elevated inflammation, cortisol) 13 13

Positive Stress vs. Toxic Stress Increased cardiac output Increased available glucose Enhanced immune functions Growth of neurons in hippocampus & prefrontal cortex Toxic Stress Hypertension & cardiovascular diseases Glucose intolerance & insulin resistance Infection & inflammation Atrophy & death of neurons in hippocampus & prefrontal cortex This is when you go from being stressed to being stressed out. When you are stressed, your body activates a sympathetic response which leads to increased cardiac output. When you are stressed out, you can’t shut off the sympathetic response which in the long run leads to hypertension and cardiovascular diseases When you are stressed, your body activates the HPA axis to produce cortisol which increases blood glucose as fuel. When you are stressed out, your body can’t shut off the HPA axis which in the long run leads to glucose intolerance and insulin resistance. When you are stressed, your immune functions are actually enhanced. But when you are stressed out, as we talked about, you become more susceptible to infection and inflammation. When you are stressed, your hippocampus and prefrontal cortex actually grow in size. These are learning centers inside your brain that help you learn from your mistakes. But when you are stressed out, these neurons don’t grow; they atrophy and die. So acute stress helps you learn; that’s why we keep such vivid memories of a stressful event like when Kennedy was shot or 911. But chronic stress makes you forget and you start to lose your memory if you are under chronic stress.