• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/48

Click to flip

48 Cards in this Set

  • Front
  • Back
Depression is associated with
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
Neurogenesis in people w/ depression
i. Neural growth factors are low ie: BDNF (plasticity), NGF, FGF
neurogenesis in people with depression may reflect
abnormalties in neurogensis or neurotropic factors (NGF, FGF, BDGF)
Patients treated with SSRI present
iii. Increased BDGF
Neurogenesis and stress
stress impairs it. Antidepressants promote neurogensis. Takes time for drugs to work, 4 weeks
-vii. Stress impairs neurogenesis and drug to combat is Prozac
v. Stress releases cortisol that suppress
BDNGF and volume of hippocampus. Causes decrease in dendrtic branching and spines.
c. Inheritability of depression
i. 2-3x risk for MDD with 1st degree relative
ii. 60% btwn monozygotic twins compared to 20%
Genetics ‐ BP
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)
Why not one gene?
Because depression is a heterogeneous disorder that is not just one entity (different subtypes of depression), with different biological, psychological, and social causes
Monoamine Hypothesis
Posits that affective disorders stem from a deficiency or imbalance in brain monoamines
-Derived from antidepressant treatments that work on serotonin, norepinephrine, and dopamine
Serotonin (5HT) relation to suicide, depression, stress
-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
depression can be induced by
tryptophanrestriction (tryptophan is a precursor to 5HT)
Abnormalities in CSF and urinary concentrations of monoaminergic metabolites associated with
depression and mania
Norepinephrine and Dopamine are thought to be
low in depression
Impaired glutamate metabolism can produce
depressive‐like behaviors in animal models
Preliminary trials of riluzole and ketamine show
antidepressant efficacy
Increaseddopminergicactivityinmania(thought to be why
D2 antagonists work in mania)
increase calcium influx into cells associated with
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
GSK‐3B activity in bipolar
Evidence of increase
GSK 3B thought to increase
cell death and causes disturbances in circadian clock
VPA and lithium inhibit
GSK‐3B
General Anxiety, obsessional thoughts related to
Serotonin dysfunction
Anhedonia, psychomotor retardation associated with
Dopamine dysfunction
Panic assoiated with
Gaba dysfunction
fatigue related to
Norepineprhine dysfunction
New brain cells develop throughout
lifespan
BDNF
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
Evidence for neurogenesis hypothesis
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
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
chronically and excessively stressed and CRH is at higher levels and stay elevated for longer periods of time
Cortisol and CRH have been shown to cause damage to hippocampal neurons by
causing decreased dendritic branching and decrease in pyramidal neuron spines
Hippocampal volume decreases associated with
depression
• Hippocampus is also involved in regulating HPA, so damage to hippocampus will cause further increases in stress hormones
Brain derived Neurotropic growth factor are inibited by
Stress and glucocorticoids
hippocampus size and depression
Decrease in volume of hippocampus is proportional to length of depression
When you get the flu, inflammatory cytokines increase which is thought to be responsible for
fatigue, fever, muscle aches aka sickness behavior. Overlap with neurovegetative symptoms of depression
what cytokines are involved in major depression
Elevations in IL‐2, IL‐6, TNF‐α, IFN are
Preferred treatment for hepatitis C involves
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
Depression and sleep
80% MDD have difficulty maintaining and initiating sleep
sleep patterns related to depression
-DecreasedREMsleeplatency,increasedREM
sleep times, shifting of REM to first part of night
-Decreasedslowwavesleep
• Increasesleeplatency,increasedwakening
(especially early morning)
what can be done to treat sleep and depression
Antidepressantsgenerallyreversedepressive changes in sleep architecture (increase REM latency and decrease REM sleep, and put REM more towards later part of night)
Decreased need for sleep is a symptom of
mania. nsomnia is a known trigger for manic
episodes
• Increase light suppression of melatonin in bipolar patients
common treatment for bipolar disorder,
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
Brain Imaging findings in depression
Decreased frontal blood flow (~7 %)
• Lower hippocampal volume
• Gray matter volumes decreases in anterior cingular, orbitofrontal cortex
• White matter hyperintensities associated with LLD
Characteristics of Depression are relatively consistent across
cultures
LOSSES that cause sadness are of
reproductive
resources
• Money, a mate, reputation, health, relatives, friends....
• These things, in theory, would have increased reproductive success (evolutionarily speaking)
Depression is a response to complex problems and functions to minimize disruption of rumination (depression as cognitive adaptation) by:
Reducing distracting stimuli (anhedonia)
– Decreasing psychomotor activity to reduce exposure to distracting stimuli
Novel Aspects in Modern Life & Depression as an Epidemic
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
Novel Environmental Factors: Disintegration of Communities
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
Bipolarseemstobecorrelatedwithcreativity,artistic talent, and striving for goals
• Hypomaniaattimescanbeassociatedwith
ncreased productivity
• increasedpromiscuitymayhavehelpedtopropagate the genes