NROSCI 1030Exam # 4 (Final) Study Guide Lectures: 22 - 25Lecture 22 (4/8): DepressionGeneral 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 anhedoniao Appetite changeso Sleep changeso Psychomotor agitation or retardationo Fatigue/low energyo Inappropriate guilto 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 relapseLecture 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 isdeactivated; 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 toDXM 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 changeStudying Depression- 2 problems with studying depressiono few animal modelso 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); fixedwith 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 Struggleo Sulkingo 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 AChTreatments- 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 intervalbetween