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Front 1

Depression is associated with

Back 1

1. Low serotonin (mood/low tryptophan/stress obsessional), and low norepinephrine (fatigue), GABA (panic) and dopamine (pleasure)
ii. Impaired glutamate metabolism
iii. Hypothalamic pituitary adrenal axis regulates stress with ACTH and CRH. Stressed people have pathway stimulated for longer periods
iv. Cortisol lead to believe with decreased branching, volume in hippocampus

Front 2

Neurogenesis in people w/ depression

Back 2

i. Neural growth factors are low ie: BDNF (plasticity), NGF, FGF

Front 3

neurogenesis in people with depression may reflect

Back 3

abnormalties in neurogensis or neurotropic factors (NGF, FGF, BDGF)

Front 4

Patients treated with SSRI present

Back 4

iii. Increased BDGF

Front 5

Neurogenesis and stress

Back 5

stress impairs it. Antidepressants promote neurogensis. Takes time for drugs to work, 4 weeks
-vii. Stress impairs neurogenesis and drug to combat is Prozac

Front 6

v. Stress releases cortisol that suppress

Back 6

BDNGF and volume of hippocampus. Causes decrease in dendrtic branching and spines.

Front 7

c. Inheritability of depression

Back 7

i. 2-3x risk for MDD with 1st degree relative
ii. 60% btwn monozygotic twins compared to 20%

Front 8

Genetics ‐ BP

Back 8

First degree relatives 7 times more likely to develop Bipolar disorder
Concordance is 50‐70%form onozygotictwinsand 20% for dizygotic twins
• Notjustonegene,butmanygenesconveyrisk(can be different genes for different people)

Front 9

Why not one gene?

Back 9

Because depression is a heterogeneous disorder that is not just one entity (different subtypes of depression), with different biological, psychological, and social causes

Front 10

Monoamine Hypothesis

Back 10

Posits that affective disorders stem from a deficiency or imbalance in brain monoamines
-Derived from antidepressant treatments that work on serotonin, norepinephrine, and dopamine

Front 11

Serotonin (5HT) relation to suicide, depression, stress

Back 11

-Lowtryptophan,5HT,and5HIAA(metaboliteof5HT)
in postmortem suicide patients
-Decreasedexpressionof5HT2areceptorsin depressed patients
-Polymorphismsof5HT1areceptorswithdecreased affinity for 5HT have been shown to increase risk for depression when stressed

Front 12

depression can be induced by

Back 12

tryptophanrestriction (tryptophan is a precursor to 5HT)

Front 13

Abnormalities in CSF and urinary concentrations of monoaminergic metabolites associated with

Back 13

depression and mania

Front 14

Norepinephrine and Dopamine are thought to be

Back 14

low in depression

Front 15

Impaired glutamate metabolism can produce

Back 15

depressive‐like behaviors in animal models

Front 16

Preliminary trials of riluzole and ketamine show

Back 16

antidepressant efficacy

Front 17

Increaseddopminergicactivityinmania(thought to be why

Back 17

D2 antagonists work in mania)

Front 18

increase calcium influx into cells associated with

Back 18

Bipolar disorder
-Increase in CAMP reponsiveness
ncrease in G proteins, seen in frontal and temporal lobes
• G protein increase seen in untreated mania patients monocytes
• All of these increase neurotransmission
• Excitotoxicity may contribute to neurodegeneration seen in bipolar, and excitability may contribue to manic state

Front 19

GSK‐3B activity in bipolar

Back 19

Evidence of increase

Front 20

GSK 3B thought to increase

Back 20

cell death and causes disturbances in circadian clock

Front 21

VPA and lithium inhibit

Back 21

GSK‐3B

Front 22

General Anxiety, obsessional thoughts related to

Back 22

Serotonin dysfunction

Front 23

Anhedonia, psychomotor retardation associated with

Back 23

Dopamine dysfunction

Front 24

Panic assoiated with

Back 24

Gaba dysfunction

Front 25

fatigue related to

Back 25

Norepineprhine dysfunction

Front 26

New brain cells develop throughout

Back 26

lifespan

Front 27

BDNF

Back 27

Promotes synaptic plasticity, neuronal growth, neuronal spine formation, especially in hippocampus
• Also helps cell survival and resilience
• Reduces apoptosis
• Shown to be low in patient with depression
• Increased BDNF expression in hippocampus of depressed patients treated with antidepressants compared to untreated

Front 28

Evidence for neurogenesis hypothesis

Back 28

Stress impairs adult neurogenesis
• Antidepressants promote neurogenesis
• Prozac has been shown to increase hippocampus synaptogenesis in rats after 5 days treatment
• Postmortem studies show the hippocampi of MDD pts have more neural progenitor cells compared to untreated MDD pts

Front 29

When exposed to chronic or extreme stress, cortisol, ACTH, and CRH levels are at higher levels, and stay elevated for longer periods of time
• Evidence that negative feedback mechanism of cortisol fails when

Back 29

chronically and excessively stressed and CRH is at higher levels and stay elevated for longer periods of time

Front 30

Cortisol and CRH have been shown to cause damage to hippocampal neurons by

Back 30

causing decreased dendritic branching and decrease in pyramidal neuron spines

Front 31

Hippocampal volume decreases associated with

Back 31

depression
• Hippocampus is also involved in regulating HPA, so damage to hippocampus will cause further increases in stress hormones

Front 32

Brain derived Neurotropic growth factor are inibited by

Back 32

Stress and glucocorticoids

Front 33

hippocampus size and depression

Back 33

Decrease in volume of hippocampus is proportional to length of depression

Front 34

When you get the flu, inflammatory cytokines increase which is thought to be responsible for

Back 34

fatigue, fever, muscle aches aka sickness behavior. Overlap with neurovegetative symptoms of depression

Front 35

what cytokines are involved in major depression

Back 35

Elevations in IL‐2, IL‐6, TNF‐α, IFN are

Front 36

Preferred treatment for hepatitis C involves

Back 36

interferon. In the first stages of treatment, fatigue, malaise, anorexia,, and pain can occur (sounds similar to sickness behavior, eh?)
• Later (1‐3 months) 1/3 develop depression. (paxil shown to prevent this depression, but not sickness behavior)
• So elevation of inflammatory molecules can be associated with depression and we can prevent this depression with antidepressants

Front 37

Depression and sleep

Back 37

80% MDD have difficulty maintaining and initiating sleep

Front 38

sleep patterns related to depression

Back 38

-DecreasedREMsleeplatency,increasedREM
sleep times, shifting of REM to first part of night
-Decreasedslowwavesleep
• Increasesleeplatency,increasedwakening
(especially early morning)

Front 39

what can be done to treat sleep and depression

Back 39

Antidepressantsgenerallyreversedepressive changes in sleep architecture (increase REM latency and decrease REM sleep, and put REM more towards later part of night)

Front 40

Decreased need for sleep is a symptom of

Back 40

mania. nsomnia is a known trigger for manic
episodes
• Increase light suppression of melatonin in bipolar patients

Front 41

common treatment for bipolar disorder,

Back 41

Lithium, activate clock genes in cell cultures (Mutations on clock genes associated with
bipolar). Lithium also hasbeenshowntoincreasegreymatter in bipolar patients, moreso in caudate, prefrontal cortex, and hippocampus. This effect is not seen in non bipolar patient

Front 42

Brain Imaging findings in depression

Back 42

Decreased frontal blood flow (~7 %)
• Lower hippocampal volume
• Gray matter volumes decreases in anterior cingular, orbitofrontal cortex
• White matter hyperintensities associated with LLD

Front 43

Characteristics of Depression are relatively consistent across

Back 43

cultures

Front 44

LOSSES that cause sadness are of

Back 44

reproductive
resources
• Money, a mate, reputation, health, relatives, friends....
• These things, in theory, would have increased reproductive success (evolutionarily speaking)

Front 45

Depression is a response to complex problems and functions to minimize disruption of rumination (depression as cognitive adaptation) by:

Back 45

Reducing distracting stimuli (anhedonia)
– Decreasing psychomotor activity to reduce exposure to distracting stimuli

Front 46

Novel Aspects in Modern Life & Depression as an Epidemic

Back 46

Mass Communications (TV, movies, etc): make a more competitive group, while destroying more intimate social networks
• Competition is amongst the billions, not the hundreds
• Your ability to be the ‘best’ at anything has diminished by being compared globally, not just locally
• More awareness of depression

Front 47

Novel Environmental Factors: Disintegration of Communities

Back 47

Modern technology dissolves supportive social groups
• Extended families dissolves as individuals scatter to pursue economic welfare
• The nuclear family: continuously evolves as divorce rates climb, and more people become single parents

Front 48

Bipolarseemstobecorrelatedwithcreativity,artistic talent, and striving for goals
• Hypomaniaattimescanbeassociatedwith

Back 48

ncreased productivity
• increasedpromiscuitymayhavehelpedtopropagate the genes