WEEK 10 BODY OVER MIND Sickness Behavior Bidirectional interactions between brain and immune system Stress effects on inflammation and health and inflammation effects on the brain and behavior Constellation of cognitive behavioral and emotional changes that occur when you are sick Fatigue sleep disturbance cognitive disturbance depressed mood social withdrawal What causes sickness behavior Pro inflammatory cytokines evidence from animal and human studies show that proinflammatory cytokines in body lead to changes in mood and behavior Animal Studies of Sickness Behavior When you inject pro inflammatory cytokines into healthy animals you get Decreased motor activity Social withdrawal Reduced food and water intake Increased slow wave sleep Altered cognition aka memory problems Anhedonia depression like symptoms Cytokine antagonists block effects Adaptive Value of Sickness Sickness behavior is thought to help fight infection and reduce spread of infection Reduced activity leads to reduced energy expenditure Can then redirect this energy into immune response and can also use energy to increase body temperature to a point where pathogens aren t as effective Immobilization reduces predator threat while ill Social withdrawal helps prevent spread of infection Why is this Important for Behavioral Scientists The symptoms caused by cytokines look very similar to the symptoms seen in psychiatric and medical populations Depressed patients cancer patients patients with autoimmune diseases insomnia etc Depression Major public health problem that affects about 20 of the population Significant negative effect on quality of life Also associated with development and progression of CVD and other diseases as well as early mortality Depression and Sickness Behavior Symptoms of Major Depressive Disorder Fatigue Symptoms of Sickness in Animals Reduced activity Sleep problems Cognitive problems Anhedonia loss of interest Feelings sad guilty or worthless Sleep problems Cognitive problems Anhedonia loss of interest Depression and Inflammation I Depressed individuals show increased inflammation Higher levels of inflammatory markers at rest and elevated inflammatory response to stress Increased inflammatory activity at rest and after stress in depressed patients Baseline CRP predicted development of MDD over 10 year period in sample of never depressed women Depression and Inflammation II Acute cytokine induction leads to symptoms of depression in healthy individuals Chronic cytokine administration leads to major depressive disorder Increased social disconnection depressed mood depression level Cancer Chronic Cytokine Administration Cancer patients treated with interferon showed elevated depressive symptoms blocked by paroxetine an anti depressant Cancer Related Behavioral Symptoms Fatigue depression sleep disturbance and chemo brain are common side effects of cancer treatment Are these normal responses to the stress of cancer diagnoses or driven by proinflammatory cytokines Cancer Related Fatigue Distressing persistent subjective sense of physical emotional and or cognitive tiredness or exhaustion related to cancer and or cancer treatment that is not is not proportional to recent activity and interferes with usual functioning Different than normal fatigue More pervasive debilitating longer0lasting Physical mental and emotional components Not relieved by adequate sleep or rest Very prevalent most common and distressing side effect of cancer and its treatment experienced in up to 95 patients What causes it Multifactorial can be influenced by a variety of demographic psychosocial behavioral medical and biological factors Inflammation and CRF Studies have documented an association between inflammation and fatigue throughout the cancer trajectory Inflammation and Fatigue during RT Inflammation and fatigue 1 month post treatment 2 5 years post treatment 5 Years post treatment Cytokine and Fatigue in Healthy Individuals Is inflammation associated with fatigue in healthy individuals Inflammatory markers correlated with fatigue cross sectionally and longitudinally in two large scale studies Relevance for Daily Life Might minor alternations in cytokine levels help explain our daily fluctuations in mood energy and cognitive functioning Low level cytokine induction leads to negative mood Do anti inflammatories that we regularly take for minor physical aches an pains influence our mood Subjects randomly assigned to take either Tylenol or placebo twice a day Everyone reported their hurt feelings at the end of the day and those assigned to Tylenol showed a decline in hurt feelings Do medications that block inflammation reduce depression and fatigue Tyring and colleagues used a medication Etanercept that blocks pro I inflammatory cytokines for patients with psoriasis The medication improved the psoriasis and led to reductions in depression and fatigue Gut Microbiota Gut Brain Axis The gut has long been known to send signals to the brain and growing evidence tells us that microorganisms in the gut also signal the brain and influence behavior The human GI tract is inhabited by 1X1013 14 microorganisms More than 10 times the number of human cells in our body Colonization of the gut with these bacteria starts at birth and alterations in the gut Microbiota influences health Can use germ free animals to study the effects of the micro biome because there are no bacteria in the gut Germ free animals show altered physiological and behavioral responses to stress You can make an anxious strain of mouse calmer by colonizing it with gut bacteria from a calm mouse strain Probiotics and Behavior You can alter the composition of the gut Microbiota with probiotics Certain probiotic cocktails lead to decreases in anxious and depressive like behavior in animal models Microbiome and the Immune System There are complex interactions between the Microbiome and the immune system Exposure to our old friends may keep the immune system in check Old friends environmental organisms that we evolved with especially helminthes worms Old friends and Inflammatory Diseases With modern sanitation our exposure to helminthes has dramatically increased which could be a possible explanation for elevated rate of inflammation associated diseases The Power of Health Behaviors Sleep Sleep predicts mortality and a study conducted with 1 3 million people showed that people who slept for less than 7 hours a night have 12 greater risk of mortality long sleepers have 30