Depression

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Depression
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Depression

• Known as a Mood/Affective Disorder
• Affect emotions
• Major Types
• Bipolar
• Unipolar
• Seasonal Affective Disorder

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Depression

• Unipolar (major depression)
• Most common affective disorder
• 19 million Americans/year (17)
• 11 million clinical major depression
• 15 parasuicide
• Good newsMost effectively treated

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Depression
Unipolar (major depression) Problems with
diagnosis?
Both a mental disorder normal mood state
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Depression
Problems with diagnosis
Reactive-Exogenous triggered by an obvious event
Endogenous No trigger No obvious event
Duration Intensity
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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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Cognition
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Physical
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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 Support

• CSF 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
• -Healthyno effect of diet or cocktail
• PET shows prefrontal cortex trypto less

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Evidence in Support

• Antidepressants Work!..so, monoamine
• agonists
• Monoamine Antagonist depression
• ex Reserpine (Rauwolfia serpentina)
• 100s years ago used to
• calm insanity
• treat hi BP 15 got depressed

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Evidence Refuting the Monoamine Hypothesis

• Antidepressants Workin 80 of the
• clinical population
• whats 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
• effectalthough in the brain

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Evidence Refuting the Monoamine Hypothesis
Neurogenesis Theory of Depression
Dentate Gyrus Hippocampus
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Antidepressant increase neurogenesis in
hippocampus
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
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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 Biochemical Therapies
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Antidepressants

• Monoamine Oxidase Inhibitors (MAOIs)
• Tricyclics
• Selective Monoamine Reuptake
• Inhibitors (SSRIs)

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Monoamines

• Catecholamines 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 interaction
• drug 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 MAOI
• headaches 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
structure Includes 3-ring structure 2 benzene
rings 1 central seven membered ring
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Tricyclics
works by preventing presynaptic reuptake
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Tricyclics
1st tricyclic Imipramine (Tofranil) serend
ipity! - 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 (SertralineZoloft, ParoxetinePaxil
• (Fluvoxamine Luvox, CitalopramCelexa)
• Side Effects
• SSRIs do not effect
• MAO little risk of hypertension
• Do 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)