Psyc 4130 1nd Edition Lecture 34 Outline of Last Lecture I Disorders of Affect II Bipolar Disorder III Depression IV Diagnostic Criteria Highlights V Signs and Symptoms VI Common Comorbidities VII Monoamine Hypothesis VIII Evidence for MA Hypothesis IX Resolving Lagtime Issues X BDNF XI MAR BDNF Signaling Cascade XII MA AutoR Overexpression Outline of Current Lecture I Tigerring MDD II Autoreceptor Downregulation III Heritability IV 5 HTT Polymorphisms V Counterintuitive Case of 5 HTT VI 5 HTT and Depression VII Anatomy of MMD VIII MAOIs IX Cheese Effect X TCAs XI TCA Overdose XII 2nd Generation Current Lecture Triggering MDD Relentlessly elevated levels of cortisol lead to hippocampal desentization atrophy and amygdalar sensitization Common endpoint Decreased MA activity Autoreceptor Downregulation RX may lead to autoreceptor downregulation These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute In turn the signaling cascade leading to monoamine synthesis is normalized Other interventions can do this as well o White box therapy exercise o Figure 16 21 exercise and neurogenesis o Electroshock therapy ECD o sgACC Figure 16 19 20 Subgenual ACC Heritability Close relatives of people with severe disorders are ten TIMES more likely to be affected Nearly 70 concordance rate for MZ twins vs 13 for DZ RORA gene involved in circadian rhythm regulation has strongest association with MDD 5 HTT Polymorphisms Responsible for reuptake promoter region for 5 HTT The allele for the promoter region for 5 HTT comes in two forms long and short Promoter regions are upstream regulatory DNA which control Individuals with one or two short alleles display greater amygdala activation when viewing pictures of fearful or angry faces Counterintuitive Case of 5 HTT Short alleles code for transporter that is less effective in removing 5 HT from synapse What happens to 5 HT levels over time This is the type associated with depression Too much synaptic 5 HT during development may tend to predispose people to depression later in life Abnormal sleep patterns reduced motivation et cetera 5 HTT and Depression A longitudinal study conducted by Caspi and colleagues 2003 followed 847 people for more than twenty years beginning at age three Recorded major negative life events e g child abuse deaths of family members romantic disasters major illnesses employment crises et cetera MDD and suicide go up as a function of the number of negative events Expected But this association was much stronger in people with two short alleles for the 5 HTT promoter Gene X environment INTERACTION MDD sufferers with two long alleles are more likely to respond to SSRIs and drug efficacy is more likely to last And they even respond better to PLACEBO Anatomy of MDD Overactive amygdala Drevets 1992 and Links 1996 showed that MDD is associated with increased regional blood flow and metabolism in the amygdala Abercrombie 1998 showed a positive correlation between depression severity and amygdala activation Underactive medial PFC The subgenual ACC is overractive in depressed patients Drevets et al 1997 This same region is hyper responsive during dipolar mania The dorsal ACC not the subgenual and amygdala are reciprocally connected and mutually inhibitory dACC inhibition of the amygdala is stronger in individuals with two long alleles for 5 HTT It s suggested that the dACC is in essence providing the amygdala with a reality check o Amygdala in freak out panic mode dorsal ACC is like chill out inhibits it The reality check bounces in MDD leading to escalating MAOIs MAOIs were first deployed in the late 1950s The first MAOI iproniazid was being used to treat tuberculosis when it was serendipitously discovered to have mood elevating effects MAO is an enzyme that acts in the presynaptic axon terminal to deaminate DA NE and 5 HT MAOIs block this activity typically irreversibly It takes several weeks to biomanufacture more MAO Cheese Effect Foods containing large amounts of a derivative of tyrosine while on a MAOI may lead to hypertensive crisis Common culprits Cheese wine most dairy products e g yogurt pickled smoked or marinated meats sour cream soy sauce teriyaki sauce tofu avocados bananas pineapple peanuts raspberries yeast et cetera TCAs Tricyclic Antidepressants Introduced in 1950s Mechanism of Action RI of and How do they work TCA Overdose Toxic effects are observed at about 10 times the normal therapeutic dose May include severe hypertension cardiac arrythmias abnormal electrical activity of the heart seizure and death nd 2 Generation Thirty years after the introduction of the TCAs a reuptake inhibitor that selectively engage 5 HTT was deployed following a decade of drug research 1986 saw the deployment of prozac first SSRI fluoxetine
View Full Document
Unlocking...