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
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
Animal testsAnimal tests
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)
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
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
Physiological causesPhysiological causes
Serotonin Serotonin + Norepinephrine + + Norepinephrine + DopamineDopamine
Brain Derived Neurotrophic Brain Derived Neurotrophic FactorFactor(BDNF)(BDNF)“brain food”Neuropeptide
Brain Derived Neurotrophic Brain Derived Neurotrophic FactorFactor(BDNF)(BDNF)In depressed individuals
◦Dereased Hippocampus Prefrontal Cortex
◦Increased Ventral Tegmental Area Nucleus Accumbans
HHypothalamic – ypothalamic – PPituitary – ituitary – AAdrenaldrenal
axisaxisSystem which controls stress
responses
GeneticGeneticDepression is heritableAll the mentioned systems have
mutationsHaving genetics that make you
prone to depression doesn’t mean you will have it….
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.”
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
Methyl
Group
DNA methyl
Transferase
DNA Demethylase?
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
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
Methyl groups
Acetyl groups
Histone Deacetylase
(HDAC)
Histone Demethylase
(HDM)
Histone Acetyltransfer
ase (HAT)
Histone Methyltransfer
ase (HMT)
The End
was that so bad?
Active DNA demethylation.
Wolffe A P et al. PNAS 1999;96:5894-5896
©1999 by National Academy of Sciences