Symptoms of Depression Can’t feel joy – Anhedonia ◦ Usually withdraws from these activities...
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Symptoms of DepressionSymptoms of DepressionCan’t feel joy – Anhedonia
◦Usually withdraws from these activities
Too little / Too much sleep◦Fatigue
Cognitive problems◦Can’t concentrate
Feelings of guilt or worthlessnessSuicide
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People in the US who..People in the US who..Currently have major depression
◦1 in 20
Will have major depression in their life◦1 in 5
www.cdc.gov/nchs
Kessler 2005
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Animal testsAnimal tests
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Learned Helplessness ModelsLearned Helplessness Models(how long did it take them to stop (how long did it take them to stop
moving?)moving?)
Forced Swim Test
Tail SuspensionTest
(Sleepy, not dead)
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Motivation / Reward ModelsMotivation / Reward Models(Doing less of what you used to do)(Doing less of what you used to do)
Sucrose Preferenc
e
Social Avoidanc
e
Sexual Preferenc
e
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Brain structure changeBrain structure changeDecrease in size of
◦Hippocampus Cognition & learning
◦Pre Frontal Cortex?
Emotional control Decision making
Amygdala (mixed results) Emotional learning Most don’t see any change
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Physiological causesPhysiological causes
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Serotonin Serotonin + Norepinephrine + + Norepinephrine + DopamineDopamine
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Brain Derived Neurotrophic Brain Derived Neurotrophic FactorFactor(BDNF)(BDNF)“brain food”Neuropeptide
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Brain Derived Neurotrophic Brain Derived Neurotrophic FactorFactor(BDNF)(BDNF)In depressed individuals
◦Dereased Hippocampus Prefrontal Cortex
◦Increased Ventral Tegmental Area Nucleus Accumbans
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HHypothalamic – ypothalamic – PPituitary – ituitary – AAdrenaldrenal
axisaxisSystem which controls stress
responses
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GeneticGeneticDepression is heritableAll the mentioned systems have
mutationsHaving genetics that make you
prone to depression doesn’t mean you will have it….
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EpigeneticsEpigenetics ‘the study of
changes in genome function that occur without a change in DNA sequence‘
“DNA is just a tape carrying information, and a tape is no good without a player. Epigenetics is about the tape player.”
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What will you find in the What will you find in the papers?papers?DNA
◦Methylation On the Cytosine at CpG sites Inhibits gene expression
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Methyl
Group
DNA methyl
Transferase
DNA Demethylase?
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What will you find in the What will you find in the papers?papers?Proteins
◦Methyl cytosine binding protein (MeCP) Bind methylated cytosine Further repression
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What will you find in the What will you find in the papers?papers?Histones
◦Acetylation Increases expression
◦Methylation Usually decreases expression
Lysine 4 – activates Lysine 9 – inhibits Lysine 27 - inhibits
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Methyl groups
Acetyl groups
Histone Deacetylase
(HDAC)
Histone Demethylase
(HDM)
Histone Acetyltransfer
ase (HAT)
Histone Methyltransfer
ase (HMT)
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The End
was that so bad?
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Active DNA demethylation.
Wolffe A P et al. PNAS 1999;96:5894-5896
©1999 by National Academy of Sciences