Lecture 8 Flashcards
How is depression diagnosed?
Symptoms of low mood need to persist of 2 weeks and abrupt normal life.
How can depression arise?
40% inherited, can arise due to concussions and can’t be narrowed down to a single brain region
What is unipolar depression?
mood swings in one
low mood
anadenia= inability to take pleasure from activities
extreme loss/gain of weight
reactive type (75%)= specific trigger e.g. stressful situations
endogenous= no clear cause
What is bipolar depression?
Low mood alternating with mania
extreme positive feelings characterised with euphoria and aggression or irritability
caused by stressful situations
40% have family with depression but no gene related and no singular brain region
What are the typical symptoms of depression?
libido loss= loss of sex drive anhedonia low mood, aggression, feelings of guilt apathy= extreme loss or gain of weight sleep disturbances= insomnia or excessive sleeping
What are the brain regions effected by depression?
- Mesolimbic dopamine circuit= increase in BDNF
- Decrease in BDNF in the hypothalamus due to cortisol
- Amygdala= associated with fear response
- Ghrelin95 and leptin 96= metabolic hormones released due to hypothalamus activity
- Increased stimulation in nucleus accumbans alleviates depression. Release of dopamine mediates suseptability of social stress
- Limbic system and ventral tegmental area= involved in mood and reward
What is postnatal depression?
Depressed mothers can have depressed babies
occurs 2-8 weeks after birth
brainwaves in the baby can be affected and can grow up to have depression
mother’s behaviour can cause epigenetic changes in the baby
Describe depression and society
Many people don’t get help
counselling and antidepressants are recommended
anti-depressants are important due to change in brain chemistry that can only be reversed by drugs even though cause is gone
How are animal models used to test antidepressants?
- Swim test= swim until they give up and become depressed
- Suspend from tail then give up
- place in confined space
- Stressful situations for several weeks that is unpredictable= they acquire similar brain activity to stressed humans
Give them ADs and they persist to escape stressful situations- more immediate effects for acute stress not chronic
What are the physical causes of depression?
No change in gross anatomy but little evidence in pathology= increase in cortisol
What is the monoamine hypothesis?
Drugs that cause monoamine depletion e.g. reserpine cause depression
How do MOA inhibitors relieve symptoms of depression?
They inhibit the depletion of monoamines- take a while to work as they need to alter transcription
What else is implicated in chemical depression?
BDNF binds to trk B which is controlled by serotonin
glutaminergic neurodegeneration is also implicated
increase in CREB in hippocampus
How are receptors effected in depression?
5HT 1b R= beneficial change in transcription- increase p11 in the cortex- in depression they have reduced signalling and causes apoptosis and loss of synapses
glutamate causes excess activation of NMDARs which results in neurodegeneration
Reserpine
Causes depletion of monoamines which causes depression and Parkinson’s
Iproniazid
first specific MAO inhibitor
How do tricyclic anti-depressants work? e.g. imaprimine
They are involved in the reuptake of NA and 5HT- inhibit their transporters
What do monoamines modulate?
dopamine from ventral tegmental area
5HT from dorsal raphe
NA from local coeruleus
areas known to control awareness, emotion alertness
Moclobemide
MOA inhibitor- more selective for A type in CNS
side effects= increase in sympathetic drive and NA
phenylzine
MAO inhibitor like moclobemide. Irreversible, non-competitive inhibitor
fluoxetine
selective 5HT uptake inhibitors- can be not that effective due to NA component
MA R antagonists
Alpha 2 adreno and 5HT1/2 have been implicated
What is the principle action of ADs?
They inhibit breakdown of monoamines- 5HT>NA>DA
Have side effects= NA depletion from vesicles
What is the cheese effect?
Cheese, wine and other foods contain tyramine- when you have MAOI= more monoamines leaking out of the neurons which results in sympathetic discharge therefore increase in BP
