depression
DESCRIPTION
Depression. Depression. Known as a Mood/Affective Disorder Affect = emotions Major Types Bipolar Unipolar Seasonal Affective Disorder. Depression. Unipolar (major depression) Most common affective disorder 19 million Americans/year (17%) - PowerPoint PPT PresentationTRANSCRIPT
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DepressionDepression
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DepressionDepression•Known as a Mood/Affective Disorder
Affect = emotions
Major Types
•Bipolar
•Unipolar
•Seasonal Affective Disorder
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DepressionUnipolar (major depression)
•Most common affective disorder
•19 million Americans/year (17%)•11 million clinical & major depression•15% parasuicide•Good news…Most effectively treated
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DepressionUnipolar (major depression)
Problems with diagnosis?
Both a mental disorder & normal mood state
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Depression
Reactive-Exogenous triggered by an obvious event
Endogenous No trigger No obvious event
Duration & Intensity
Problems with diagnosis
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•Anhedonia (experience pleasure)•Weight gain or loss•Hypersomnia, insomnia• Fatigue, loss of energy• feelings of worthlessness guilty• difficulty concentrating
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Clinical Depression
(5 symptoms)
(2 symptoms)
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MOOD
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Cognitio
n
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Physical
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3
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Genetic Risk Concordance rate of 68% (monozygotic) Concordance rate of 15% (dizygotic) Family member = 10 tx more likely
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Theories of Depression(Biological)
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Most Dominant Theory of Depression
Monoamine Hypothesis of Depression
Depression is associated with an under activity at serotonergic and noradrenergic synapses
(Indolamines & catecholamines)
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Evidence in SupportCSF of depressed pt suicidal low levels of 5HIAA Post Mortem brains from depressed pt (prefontal) above avg # of 5HT & Norepi receptors upregulation
Post Mortem Suicide• low 5HT• low Norepi
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Evidence in Support- Tryptophan depletion in depressed pt (Delgado, 1990)
Put on Low Trypto. Diet (salad, corn, gelatin)
Then, amino acid cocktail (no trypto.)…so hi other amino acids
Trypto. Dropped! = relapse -Healthy…no effect of diet or cocktail…PET shows prefrontal cortex trypto less
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Evidence in Support-Antidepressants Work!..so, monoamineagonists
-Monoamine Antagonist = depression ex: Reserpine (Rauwolfia serpentina) 100’s years ago used to - calm insanity- treat hi BP = 15% got depressed
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Evidence Refuting the Monoamine Hypothesis
-Antidepressants Work…in 80% of the clinical population…what’s up with the other 20%???
-“Lag Time” time it takes a drug to work in the brain vs the time we see a behavioral effect 3 to 4 weeks to see behave effect…although in the brain
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Evidence Refuting the Monoamine Hypothesis
Neurogenesis Theory of Depression
Dentate Gyrus: Hippocampus
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Section of the dentate gyrus of the hippocampus, showing newly formed cells. These are the darker cells in the subgranular zone (SGZ), and they have been labelled with 5-bromo-2-deoxyuridine (BrdU), an analogue of thymidine.
The histogram shows that various antidepressant treatments increase the number of new labelled cells. The treatments tested include electroconvulsive shock (ECS), the MAOI tranylcypromine (TCP), the SSRI fluoxetine (FLU), and the selective norepinephrine reuptake inhibitor reboxetine (REB).
Santerelli et al, 2003, Science
Antidepressant increase neurogenesis in hippocampus
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Evidence Refuting the Monoamine Hypothesis
Neurogenesis Theory of Depression
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proliferation
survival
Exercise….
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Treatment – BiochemicalTherapies
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Antidepressants•Monoamine Oxidase Inhibitors (MAOIs)
•Tricyclics
•Selective Monoamine Reuptake Inhibitors (SSRIs)
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MonoaminesCatecholamines: Norepinephrine
Indolamines: Serotonin
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•Monoamine Oxidase Inhibitors (MAOIs)
- MAOIs block the enzyme monoamine oxidase… - MAO breaks down monoamines into inactive metabolites
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MAOIs:•Iproniazid (eye-pron-eye-a-zid)•First antidepressant (1957)
- originally marketed as rocket fuel - TX for TB
A flop!…serendipity intervened
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MAOIs:•Isocarboxazid•Phenelzine•Tranylcypromine
•Side effects:• hypertension (BP): headaches, sweating, nausea, vomiting
•Side effects represent drug interactiondrug X food
Tyramine – cheese, wine, licorice, raisins MAO breaks down tyramine= too much intracranial hemorrage (stroke)
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MAOIs:•“Cheese Effect”
Pharmacist G.E.F. Rowe wife was being treated with MAOIheadaches after eating cheese
Blackwell et al found that cheese causes a large increase in BP without MAO
increase in tyramine indirectly acts on sympathetic release of Norepi
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Tricyclics
Called tricyclics because chemical structureIncludes 3-ring structure – 2 benzene rings &1 central seven membered ring
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Tricyclicsworks by preventing presynaptic
reuptake
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Tricyclics 1st tricyclic: Imipramine (Tofranil)
serendipity!
- Synthesized in 1948 as an antihistamine
- Used in Schizophrenia – no help with psychosis but less depressed
Side effects: (safer than MAOI)- block histamine receptors: produces drowsiness- block acetylcholine receptors: dry mouth, difficulty urinating- Na+ Channels: heart irregularities
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Tricyclics Appear to work better with:
- Early morning awakenings- Loss of appetite- Weight loss- Morning depression heightened
Contraindicated for Bipolar depression can trigger the mania
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Second Generation: Selective Serotonin Reuptake Inhibitors (SSRIs) “Atypical” Antidepressants
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SSRIs: Block Reuptake
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SSRIs
-Just Like the tricyclics but selective to block serotonin uptake
Fluoxetine (Prozac) -first on the market in 1980s -most prescribed -not more effective in tx depression
* fewer dangerous side effects* effective in a wide range of
affective problems lack of self-esteem, fear of failure, OCD, Binge eating & purging (Bulimia)
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SSRIs (Sertraline:Zoloft, Paroxetine:Paxil (Fluvoxamine: Luvox, Citalopram:Celexa)
Side Effects:SSRIs do not effect:MAO – little risk of hypertensionDo not worry about food interaction
However side effect: nervousness 25% nausea-10% nausea (Prozac & Zoloft) Priapism (trazadone) - protracted & painful penile erection
Social anxiety disorder, PTSD, Panic disorder, OCD)ALSO: Selective Norepi Reuptake Inhibitors (Reboxetine)