Symptoms of Depression Can’t feel joy – Anhedonia ◦ Usually withdraws from these activities...

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