Introduction to Behavioral Neuroscience Lecture Notes PDF

Introduction to Behavioral Neuroscience PSYC 211 Lecture 24 of 24 – Stress, Anxiety, OCD, Addiction Professor Jonathan Britt Questions? Concerns? Please write to [email protected]  FMRI STUDIES OF DEPRESSION fMRI studies have not really found...

Introduction to Behavioral Neuroscience PSYC 211 Lecture 24 of 24 – Stress, Anxiety, OCD, Addiction Professor Jonathan Britt Questions? Concerns? Please write to [email protected]  FMRI STUDIES OF DEPRESSION fMRI studies have not really found consistent differences in the brains of people when they are depressed versus not depressed. Some studies found that the subgenual anterior cingulate cortex was less active in people after their depression lifted, but clinical trials targeting this region with deep brain stimulation were unsuccessful.  ELECTROCONVULSIVE THERAPY Electroconvulsive therapy (ECT) Used therapeutically to alleviate severe depression and bipolar disorder. Seizures are electrically induced by applying brief electrical shocks to the head The seizures induced by ECT often reduce symptoms within hours or days. There is often some short-term memory loss, among other side effects, but the treatment does not appear to cause any brain damage.  ROLE OF SLEEP IN DEPRESSION One of the most prominent symptoms of depression is disordered sleep. People with depression often have shallow, fragmented sleep. They also tend to awaken frequently, especially toward morning. In general, depressed people spend more time in stage 1 sleep and less time in deep, slow-wave sleep (stages 3 and 4). They also enter REM sleep soon after falling asleep, much earlier in the night than other people.  ROLE OF SLEEP IN DEPRESSION For many people, one of most effective antidepressant treatments is total sleep deprivation. Total sleep deprivation tends to have an immediate antidepressant effect (but it also leads to some degree of mania). When depression lifts after staying up overnight, it returns after a normal night's sleep. Perhaps a chemical builds up during waking hours that has some antidepressant effect, and it gets cleared away during sleep. REM sleep deprivation also works, although more slowly, over the course of several weeks (similar to SSRIs).  STRESS AND ANXIETY Stress refers to the physiological reaction to aversive or threatening situations that mobilize the body for fight or flight. Stress triggers autonomic and endocrine responses that are adaptive in the short term, however chronic stress can cause adverse effects on health over time. Stress can lead to anxiety (feelings of fear, worry, or unease), but anxiety can also come about without any obvious trigger. Anxiety is characterized by a persistent feeling of apprehension or dread in situations that are not actually threatening. Anxiety can often feel more intense than stress.  PHYSIOLOGY OF THE STRESS RESPONSE 1. Stress activates the sympathetic branch of autonomic nervous system, which causes the adrenal glands (above the kidneys) to release epinephrine and norepinephrine into the blood. 2. Stress also activates the HPA axis (Hypothalamus-Pituitary-Adrenal gland), which refers to a hormone signaling cascade that 2 increases glucocorticoid signaling in the blood. – The hypothalamus releases CRH/CRF (corticotropin-releasing hormone/factor). 1 – CRH causes the pituitary to secrete ACTH (adrenocorticotropic hormone). – ACTH causes the adrenal gland to release glucocorticoids, primarily cortisol. Overall, these autonomic and hormone responses work together to increase heart rate, blood pressure, and blood flow.  GLUCOCORTICOID SIGNALING Glucocorticoids A group of hormones (including cortisol) that are essential for survival. Acting on nearly every tissue and organ in the body, glucocorticoids function to maintain homeostasis in response to normal circadian changes in metabolism as well as in response to stress. Glucocorticoids regulate a ton of physiological processes including cardiovascular function, immune function, skeletal growth, reproduction, and cognition. They prepare the body for immediate action, making glucose and fat available for immediate use and increasing blood flow and arousal. Simultaneously, they deprioritize functions that are not needed for immediate survival, reducing growth hormone signaling, sex hormone signaling, and immune function.  CHRONIC STRESS While the short-term effects of glucocorticoids are essential for survival, persistent glucocorticoid signaling can … lead to anxiety, depression, and insomnia, as well as increase symptom severity for a variety of mental illnesses worsen cardiovascular health (increased blood pressure, heart rate, heart disease, and heart palpitations) weaken the immune system, making it harder to fight off infections and illness cause digestive problems, such as ulcers, irritable bowel syndrome, and weight gain/loss. Gastric ulcers occur when stomach acid eats though the protective lining of the stomach, producing an open sore. increase muscle tension and damage muscle tissue inhibit growth of the body (due to reductions in growth hormone signaling) cause infertility (due to reductions in sex hormone signaling) cause steroid diabetes (due to hormone-induced damage of the pancreas) cause cell death in the hippocampus, where there are tons of glucocorticoid receptors, and memory loss.  STRESS AND IMMUNE FUNCTION Stress weakens the immune system and slows the healing of flesh wounds. People experience higher rates of sickness (typically viral or bacterial infections) following periods of high stress. POSTTRAUMATIC STRESS DISORDER (PTSD) PTSD is a mental disorder that can develop after a person is exposed to one or more traumatic events, such as abuse, assault, warfare, car accidents, etc. The main symptoms include vivid and intrusive memories of the traumatic event (“flashbacks”) as well as recurrent dreams about the traumatic event active avoidance of stimuli associated with the trauma, and pronounced mental or physical distress in response to these stimuli hyperarousal and hypervigilance Persistent negative moods and feelings of hopelessness are common Symptoms interfere with social activities and increase risk for suicide. PTSD is no longer classified as an anxiety disorder since it entails multiple emotions outside the fear and anxiety spectrum, including guilt, shame, and anger. POSTTRAUMATIC STRESS DISORDER (PTSD) Most people who experience trauma do not develop PTSD, but the likelihood of developing it increases with the number of traumatic events. About 10% of women and 5% of men experience PTSD at some point. About 30% of the variance in PTSD relates to genetics. The main treatments for PTSD are cognitive behavioural therapy, group therapy, and medication. Selective serotonin reuptake inhibitors (SSRIs) are the first-line medications and benefit about half of people. PTSD has been associated with abnormalities in the HPA axis, which coordinates hormonal responses to stress. Symptom severity negatively correlates with size of the hippocampus and parts of the PFC, although it is unclear which is the cause and which is the effect.  ANXIETY DISORDERS Anxiety disorder A variety of psychological disorders characterized by unrealistic and unfounded fear and anxiety. Includes expectation of an impending disaster, muscle tension, over activity of the autonomic nervous system, and continuous vigilance for danger. Generalized anxiety Disorder characterized by excessive anxiety and worry serious disorder enough to cause disruption of daily life  ANXIETY DISORDERS People often have more than one type of anxiety disorder Social anxiety Characterized by excessive fear of being exposed to the scrutiny of disorder other people, leading to avoidance of social situations in which they may be called on to perform Panic disorder Characterized by episodic periods of severe and unremitting terror. Includes symptoms such as shortness of breath, irregular heartbeat, and other autonomic symptoms, accompanied by intense fear Anticipatory Fear of having a panic attack promotes anticipatory anxiety that anxiety sometimes leads to the development of agoraphobia Agoraphobia Fear of being away from home or other protected places  ANXIETY DISORDERS About 12% of people are affected by an anxiety disorder each year. It appears twice as often in females as males and generally begins before the age of 25. 10% of people develop social anxiety disorder at some point in their life. Another 10% develop a specific phobia.  ANXIETY DISORDERS The cause of anxiety disorders is a combination of genetic and environmental factors. Environmental risk factors include a history of child abuse and poverty. Anxiety disorders often occur with other mental disorders, particularly major depressive disorder, personality disorder, and substance use disorder. There are no obvious brain circuit disruptions in people who have an anxiety disorder, but (older) people with dementia often struggle with anxiety.  ANXIETY DISORDERS Treatment options include lifestyle changes, behavioural therapy, and medications. Lifestyle changes may include exercise, regularizing sleep patterns, and reducing caffeine intake and smoking. Cognitive behavioral therapy (CBT) is often effective and is a first line treatment. When medication is called for Selective serotonin reuptake inhibitors (SSRIs) are frequently used as a first line treatment for anxiety disorders Benzodiazepines are sometimes used, particularly in emergency settings, because of their rapid onset OBSESSIVE-COMPULSIVE DISORDER (OCD) OCD is characterized by – repeatedly having certain thoughts ("obsessions") and – a need to repeatedly check things or perform certain routines (“compulsions” or “rituals”) to an extent that it causes distress & impairs general functioning. There are a variety of symptoms, which are often clustered into 4 groups: symmetry, cleaning, hoarding, and forbidden thoughts. The “cleaning” cluster is associated with germs, bodily fluids, and contamination. The "forbidden thoughts" cluster is associated with intrusive and distressing thoughts that are violent, religious, or sexual in nature.  OBSESSIVE-COMPULSIVE DISORDER (OCD) Generally, the obsessions drive the compulsions. There may be a belief that there is some imbalance in the world, something is out of place, as well as the idea that life cannot proceed as normal while the imbalance remains. Compulsions are performed to seek relief from obsession-related anxiety, out of fear that something bad will happen if the ritualistic behaviour is not done properly. Compulsion can include obsessive hand washing, cleaning, counting, and checking things (e.g., that the doors are locked). Some people have difficulty throwing things out. Most adults with OCD recognize that their behaviors do not make much sense. They understand that their beliefs do not correspond with reality. However, they feel like they must act as though their beliefs are correct. It is very difficult for people with OCD to control their obsessions and compulsions for more than a short period of time.  OBSESSIVE-COMPULSIVE DISORDER (OCD) The prevalence is about 2% of the population. It is nearly twice as common in females than males, but the onset of symptoms is typically later in females (late teens/early twenties) than it is in males (adolescence). Symptoms usually start before age 25 in both sexes. The cause of OCD is a combination of genetic and environmental factors. Genetic factors account for ~50% of the variability. Environmental risk factors include a history of child abuse or other adverse events. Some cases have been documented following infections. Sometimes symptoms emerge after brain damage, particularly to the basal ganglia, cingulate gyrus, or prefrontal cortex. fMRI studies have found increased activity in the frontal lobes and striatum in patients with OCD OBSESSIVE-COMPULSIVE DISORDER (OCD) Treatment Treatment always involves counseling, often a version of cognitive behavioral therapy (CBT) known as exposure and response prevention, which involves increasing exposure to what causes the problems while not allowing the repetitive behavior to occur. Treatment sometimes includes antidepressants such as selective serotonin reuptake inhibitors (SSRIs) Without treatment, the condition often lasts decades. Treatment for severe cases can include a brain lesion, specifically a cingulotomy, which is the cutting of a fiber bundle between PFC and anterior cingulate. Deep brain stimulation within basal ganglia areas is an active area of research.  SUBSTANCE ABUSE DISORDERS Drug addiction is a serious, debilitating disorder. Addictive substances include alcohol, opiates, cocaine, meth, nicotine, barbiturates, and benzodiazepines. Some gene variants predispose people to becoming addicted to a specific drug. Other gene variants increase the risk of developing addiction in general. Genetic factors account for 40–60% of the risk factors for alcoholism. Alcohol consumption is not distributed equally across the population; in the United States, 10 percent of the people drink 50 percent of the alcohol. Problems with alcohol abuse include: automobile accidents liver disease (cirrhosis of the liver) heart disease and strokes pancreatitis and diabetes fetal alcohol syndrome Korsakoff's syndrome etc. (withdrawal can cause seizures and death)  REINFORCEMENT LEARNING Reinforcement learning is driven by the consequences of one’s behaviour. Addictive drugs positively reinforcer behaviour. Reinforcement is most effective when the consequences of an action are immediate (versus delayed). The speed by which the brain perceives reinforcement is thought to explain the relative addictive potential of different drugs, such as heroin vs morphine All reinforcers, natural or otherwise, elicit dopamine release in the striatum, particularly in the nucleus accumbens, and the most addictive drugs rapidly increase dopamine signaling.  PHYSICAL DEPENDENCE Tolerance When a drug effect gets smaller with repeated administration, increasingly larger doses are needed to achieve the desired effect. It is caused by compensatory mechanisms that oppose the effect of the drug. Withdrawal Appearance of symptoms opposite to those produced by drug when the drug is suddenly no longer taken Caused by presence of compensatory mechanisms (that relate to drug tolerance) Dependence refers to the physical symptoms of tolerance and withdrawal. Physical dependence (tolerance and withdrawal) are useful indicators of drug use, but they are not the same thing as addiction. Tolerance and withdrawal can occur independent of an addiction, and not all addictive drugs produce noticeable tolerance and withdrawal.  NEGATIVE REINFORCEMENT In the field of psychology, the term negative reinforcement is used to describe when a behaviour is reinforced by the removal (or reduction) of an aversive stimulus. People have argued that addiction is partially maintained by negative reinforcement, since after tolerance develops people sometimes continue to take drugs simply to prevent or reduce withdrawal symptoms. However, drug cravings and addictive behaviours far outlast any physical withdrawal symptoms. Getting through withdrawal is often the easy part.  COMORBIDITY One study in 2004 estimated that a third of all cigarettes were smoked by the 7% of the population that had some form of mental illness. There is a high level of comorbidity of drug addiction, schizophrenia, and ADHD. Most schizophrenics smoke cigarettes and nearly half are addicted to other drugs. Abnormalities in the prefrontal cortex and its interactions with the striatum and dopamine neurons may be a common factor in these disorders. Drug addicts sometimes show deficits on tasks that involved the PFC, similar to people that have brain damage in this area. In one study, the estimated total amount of cocaine taken by addicts in their lifetime correlated with reductions in PFC activity.  TREATMENTS: BLOCK THE RECEPTOR APPROACH Naltrexone A high affinity, slow onset, long-acting opioid receptor antagonist that is prescribed to alcoholics and opiate addicts for daily use. It reduces the high produced by opiates (by outcompeting opiates for the receptor binding site). It also seems to reduce cravings for food, alcohol, and other drugs in some people. Naloxone Extremely rapid (and short lived) opioid receptor antagonist that reverses the effects of an opiate overdose. (Narcan) During an overdose, people lose consciousness and stop breathing. A naloxone injection can immediately reverse these effects and even elicit withdrawal symptoms (but it is cleared away within an hour).  TREATMENTS: THE MAINTENANCE APPROACH Methadone Potent opiate that has a slower onset and offset than heroin does. It is a substitute for heroin that allows people to live more functional lives. Methadone maintenance programs require people come into a clinic each day and drink a liquid form of methadone in the presence of clinicians. Buprenorphine A high affinity, partial opioid receptor agonist that is commonly prescribed to treat opiate addiction. It strongly binds to opioid receptors but produces only a weak psychological effect while blocking the effects of other opiates. To reduce the potential for abuse (and allow people to take home pills of it), it is mixed with a little naloxone (a short-lived opiate receptor antagonist), which eliminates the euphoric rush. Varenicline A partial agonist at nicotinic (acetylcholine) receptors that is prescribed to treat nicotine addiction. Other nicotine maintenance treatments include nicotine patches, gum, vaping, etc.  TREATMENTS: THE BRAIN STIMULATION APPROACH Deep brain Researchers have been testing the efficacy of deep brain stimulation stimulation in various brain areas for the treatment of drug addition (and many other mental illnesses). and Transcranial Transcranial magnetic stimulation (TMS) is a non-invasive procedure magnetic that uses magnetic pulses to stimulate areas of the cerebral cortex. stimulation It is a relatively simple procedure with seemingly minimal side effects. Since some benefits of TMS have been reported for a variety of mental conditions, it has been approved for the treatment of major depression, OCD, smoking, and migraines. Its efficacy (for any condition) is widely debated. Very little is known about the optimal frequency, intensity, and location of stimulation for any condition, but tons of studies are currently underway. THE END Thank you!