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anxiety disorders (6).docx

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McMaster University
Richard B Day

October 26 , 2012 Psych 2AP3: Abnormal Psychology – Major Disorders Anxiety Disorders (6) HPA and Anxiety - HPA axis: responsible for generating our hormonal response to stress: glucocorticoid steroid hormones, mobilizes glucose, damps down activity of immune system, if this activation remains too high for too long can be impacted negatively, can be damaged, high blood pressure, liver damage - HPA function altered in anxiety (and depression) - Antidepressants supress HPA activity - Young stressed macaques show anxiety-, depression-like symptoms as adults, plus changes in HPA: tends to be heightened, lower activation threshold - Early experiences shape HPA reactivity, passed on epigenetically: permanently change HPA system, epigenetics in animal studies - CRH receptor genes involved? Mice lacking CRH-R1 show reduced anxiety, mice w/o CRH-R2 gene show increased anxiety: not sure if humans vary in these genes Neurotransmitters and Anxiety - monoamines serotonin, norepinephrine: drugs targeting these alleviate anxiety - increased epinephrine, reduced inhibitory GABA in anxiety disorders: GABA is primarily inhibitory - social phobia also shows dysfunction in serotonin, dopamine systems: lower D2 binding in caudate, putamen in animals – lack of exploration, lower social status - but are these causes or effects? Genetic Factors in Anxiety - parents with anxiety = children 3-5 times more likely to have anxiety: even if they don’t meet the criteria they are described as have higher anxiety than most, you can learn these tendencies (not because you have a genetic predisposition) - 41% MZ concordance rate for anxiety reaction; 4% in DZ - No one gene responsible for more than 5% of variability in anxiety: a lot of genes involved in anxiety - Heritability coefficient ~70%, probably an over estimate - 5 – 15 loci involved Candidate Genes in Anxiety - 5HT1A receptor (serotonin):  mice lacking 5-HT1A receptor show increased anxiety: serotonin can’t attach to this receptor because it isn’t there, increase anxiety  delay expression of 5-HT1A receptor for 4 weeks = adults with increased anxiety reactions: not primarily about adult brain activity  human studies suggest link between 5-HT1A receptor and anxiety, depression  we want to raise the amount of serotonin in
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