Lecture 20 Flashcards by Devon Bode

hippocratic medicine

melancholic - water - glum
choleric - fire - irritable
phlegmatic - earth - slow
sanguine - air - healthy

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psychosurgery during 16th century

excising stone of folly (madness)
(trepanation)

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what amount of US population report symptoms of major psychosis

1/3

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depression more prevalent in

women

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factors that influence likeliness of developing psychiatric disorders

race, age, gender, environment, genetics

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the word schizophrenia means

split mind

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psychosis =

general lack of contact w/ reality

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prevalence of schizophrenia =

1-2 % of population

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schizophrenia accounts for ___ of all admissions to mental hospitals

1/2

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positive symptoms =

abnormal behaviours that are gained
- hallucinations (mainly auditory)
- delusions
- erratic motor behaviour

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paranoid delusions vs persecution delusions

paranoid = people talking about you persecution = people out to get you

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negative symptoms =

loss of functions
- slow thought/speech
- emotional/social withdrawal
- blunted emotions
- chronic, do not respond well to drugs

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Disorganized schizo.

Incoherence, grossly disorganized behaviour, bizarre thinking, and flat or inappropriate emotions

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Catatonic schizo.

Marked by stupor, unresponsiveness, posturing and mutism

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Paranoid schizo.

Preoccupation with delusions; also involves hallucinations that are related to a single theme, especially grandeur or persecution

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Undifferentiated schizo.

don’t fit into any of the above

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Stress-vulnerability hypothesis

combination of environmental stress and inherited susceptibility to cause schizophrenic disorders
- genetics, family environment, psychological trauma, deviant communication, etc.

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_____ activity excessive in schizophrenic brain

dopamine

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______ ventricles evident in schizo.

enlarged

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twins have ____% concordance rate

48% - significant genetic component, but not entirely

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T/f: patients w/ schizo. have perturbed eye behaviour

ture - amygdala?

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structural changes with schizophrenic brain

enlarged cerebral ventricles (especially in males)
smaller hippocampus + amygdala
pyrimidal cells in hippocampus in disarray
loss of gray matter
cotical thinning
thicker corpus callosum
decreased frontal lobe activity
higher dopamine amounts

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DISC1 gene

disrupted in schizophrenia 1
- appears in one schizophrenic family
- mice w/ mutated version develop enlarged ventricles

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T/F: they have trouble w/ wisconsin card sorting task

yes

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drugs can effect

Ca2+ channels, survival of NTs. reuptake/release of NTs, binding NT to receptors, etc

competitive ligand (antagonist)

binds to same receptor site as endogenous transmitter

noncompetitive ligand (antagonist)

binds to a modulatory site on the receptor

agonists

activate receptors, mimic endogenous substance

binding affinity

degree of chemical attraction btwn ligand and receptor

efficacy

the ability of the bound ligand to activate the receptor

dose-response curve

graph of the relationship between drug doses and their effects

ED(50) =

50% effective dose

a drug w/ same effects at lower dose is more

potent

a lower maximal effect =

partial agonist

therapeutic index =

seperation between effective dose and lethal dose - a smaller therapeutic index is a more dangerous drug

LD = lethal dose, LD(50) =

50% of animals that took this dose died

efficacy of drugs is largely ________ in past 50 or so years

unchanged

Amphetamine psychosis

caused by repeated use of amphetamines; resembles schizophrenia with paranoia, delusions and auditory hallucinations

brain area important w/ dopamine + schizophrenia/addiction

VTA

how some antipsychotic (neuroleptic) drugs work for schizo. and amphetamine psychosis

block dopamine D2 receptors

But, dopamine and _____ pathways have large overlap, so maybe its not dopamine

serotonin

mismatch hypothesis of disease

epigenetic alterations done early in life that alter gene expression may get the expected environment wrong, therefore are now maladaptive and can increase risk of disease

bee fed royal jelly as larvae (vs. beebread) =

queen bee, even though genetically identical

royal jelly silences _____, allows queen bee fertile genes to be activated

Dnmt3

Dnmt3 is ______ in normal bees, silencing queen genes

active

queen bee example shows

how nutrition affects epigenetic (postnatal) methylation and affect outcomes

tail kinking nutritional effect

methy donor groups in diet = increased 5mC at Axin(Fu) = silenced cryptic promoter expression = decreased tail kinking - mid-gestation effect - not early embryonic

agouti mice, methyl donor depleted diet (BPA)

more tumorgenic offspring, obese, yellow coat, diabetic

IAP (agouti mice)

retrotransposon, inserts into genome near other genes, affects gene transcription and phenotype - normally silenced via methylation - metastability renders them susceptible to nutritional influences - is transcribed, reverse transcriptase produces double stranded copy, inserted into DNA

Wild type agouti mice have

brown fur bc of agouti (A) expression

Banded fur =

brown, agouti (A)

non-banded fur =

yellow, non-agouti

A(vy/a) mom + methyl supplements =

more brown coat offspring, + IAP methylation

The A(vy) metastable epiallele results from

the insertion of an IAP upstream of the transcription start site of the Agouti (A) gene

normal, banded mice _______ agouti (A) gene

express

IAP inserted just before agouti gene =

continually produce yellow phaeomelanin, making yellow, non banded mice. - can be partially silenced with the degree of methylation on cryptic promoter region, this is how we get mottled mice.

lower methylation (agouti mice)

more yellow

yellow coat = non cyclical = ectopic

yes

pseudo-agouti = cyclical = only in hair follicles

yes

w/ control diet, most offspring coats are

slightly mottled

high maternal methylation =

pseudo-agouti, brown, lean, healthier

low A(vy) DNA Methylation =

yellow

high agouti (A) expression =

brown

high A(vy) expression =

yellow

Avy = A (agouti) +

IAP, upstream

cryptic promoter LTR (of IAP) expressed =

yellow

cryptic promoter LTR (of IAP) highly methylated =

pseudo-agouti - suppression associated w/ metylation

more BPA in moms diet (agouti mice) =

more yellow

BPA + methyl donors (agouti mice) =

same as control diet (mostly slightly mottled)