NROSCI 1030 Exam 4 Final Study Guide Lectures 22 25 Lecture 22 4 8 Depression General Characteristics Mood pervasive and sustained emotion experienced internally Affect external expression of mood Lifetime prevalence 16 2 1 Female to Male ratio onset around 40 years of age 85 of patients today recover within a year with or without Tx 70 80 of people do not seek Tx due to fear of institutions or lack of awareness of depression as a real clinical disorder Key factor how the person copes with the stressor determines their outcome Loss of a parent before age 11 is a the single greatest predisposing risk for susceptibility to stress in adulthood 18 of people who grieve undergo non self limiting grief unable to recover within 2 4 months from the stressor due to loss of a loved one All socioeconomic classes are affected equally suicide is more common in Asia while guilt is more common in the United States Monozygotic concordance 60 Dizygotic 10 Symptoms and Diagnostic Criteria Duration of episodes 4 12 months Constellation of Sx anhedonia loss of interest in pleasurable things disturbed sleep late insomnia wake up earlier than usual changes in appetite psychological guilt suicidal thoughts 50 have clear diurnal variation worse in the morning DSM Criteria need 5 or more Sx present for 2 or more weeks o Depressed mood or anhedonia o Appetite changes o Sleep changes o Psychomotor agitation or retardation o Fatigue low energy o Inappropriate guilt o Recurrent thoughts of death suicidal ideation or suicidal attempt Depression with melancholia extreme anhedonia and lack of reactivity Compared to an incidence of 1 for suicide in the overall population depressed individuals have a much higher incidence of 15 women are more prone than men to conduct attempts however men have more successful attempts Biggest risk factor for suicide is a prior suicide attempt Course of illness patients usually recover spontaneously within 6 months but faster with Tx in less than 8 weeks More than 50 of patients will have a relapse Lecture 23 4 10 Depression Continued Biology Depression is a mood disorder that affects the amygdala raw emotion and cingulate cortex PFC The PFC drives the amygdala via excitatory input onto inhibitory interneurons of the amygdala like in ADHD similar circuit Drevets found no conjoined activity between amygdala and PFC for emotional state he found increased amygdala activity and decreased PFC activity negative emotion angry face amygdala was hyperactivated positive emotion amygdala hypoactivation executive cognitive control of emotion PFC is activated and amygdala is deactivated depressed individuals have no change in PFC activity and more of the amygdala activity More amygdala activity HPA axis activated increased cortisol levels in depression cortisol is always high in normals cortisol activities start at a high decrease and increase again during the day depressed individuals have a consistently high level of cortisol activity throughout the day DXM dextromethasone test synthetic glucocorticoid it bottoms out high cortisol levels depressed patients have no response to DXM possibly because all the receptor to DXM have been desensitized when they recover from a depressive incident the DXM response is re established this is known as a state dependent variable Trait dependent variable ex how the PFC reacts in schizophrenics Wisconsin card test schoziphrenics are not able to figure it out no change in PFC activity when the rules change Studying Depression 2 problems with studying depression o few animal models o therapeutic drugs have multiple actions however these drugs are effective across a population Animal model of Kluver Bucy Syndrome amygdala lesion in monkeys caused an immediate drop in social hierarchy drop in emotional reactivity looking monkey in the eye form of aggression drop in social interaction the monkeys would self isolate themselves this was partially reversed with imipramine IMI first antidepressant Probe inserted into amygdala to stimulate it you see a sham rage no cause for it fixed with antidepressants Problem with lesioning amygdala people with depression don t have a giant lesion PFC temporal lobe spared unlike with lesioning Harlow isolated infant monkey pit of despair no interaction with mom greatly emotionally crippled too intense not simulating depression well too extreme Harlow also did 6 weeks of bonding followed by depression stages of response were o Struggle o Sulking o decreased reaction to startle also exhibited social isolation when returning to group of monkeys Learned helplessness model Seligman floor was a mesh which shocked animals inescapable shock this was done to test for chronic antidepressant treatment good model for learned helplessness Social defeat model Nestler put smaller mouse in a cage with a bigger bully mouse the smaller mouse is beat up everyday then the mouse is put through a series of tests some mice were more resistant to this bullying than others Forced swim test you put a mouse in a giant beaker of water the length of time of swimming is affected by a single dose of antidepressants Tail suspension test how long he fights is used as a test for antidepressant effects Sucrose preference test for anhedonia give water deprived mice sucrose and water measure how long they drink the solution Tryptophan depletion this sends people into a deep depression not used as a model as it can t be fixed Sx look a lot like depression Genetically linked disease you need something that is consistent over a lot of generations like social defeat test The best data we have is to mimic the Sx and see if the Tx works 1950 reserpine caused clinical depression in 15 of people depletes NE DA and 5 HT alpha MPT much less potent than reserpine didn t cause clinical depression as reliably it only affected NE DA and ACh Treatments Electroconvulsive Shock Therapy ECT or ECS mostly for people who have catatonic depression it is 90 effective for people who use it it is much faster than drugs which take 3 4 weeks to be effective patients usually get 6 treatments with a 2 day interval between treatments most people see complete remission ECT leads to huge increase in monoamines it is usually done one side of brain at a time unilaterally side effects memory loss Iproniozid caused drop in depression in TB patients it was found to be an MAOI causes a big upswing in extracellular monoamines Imipramine has a structure like flourazine it is a tricyclic antidepressant