Depression Flashcards
What are symptoms of depression?
Low mood, irritability, loss of interest in daily activities, sleep disturbed, loss of appetite, difficult to concentrate, low self esteem
What parts of the brain are implicated in depression?
Cingulate cortex, nucleus accumbent, amygdala, prefrontal cortex, hippocampus
When was the monoamine hypothesis?
1965
What is suggested at the moment is implicated in depression?
Monoamines (5HT and NA), BDNF (although not yet be validated) and glutamate
What is the biology of depression?
Stress, increases glutamate, NMDA, increase apoptosis
Stress, increase CRF in hypothalamus, ACTH pituitary, cortisol release from adrenal cortex, increase bad genes transcription
NA, 5HT, BDNF decrease transcription of bad genes and increase beneficial for neurogenesis
What does Reserpine do?
Produces depression and Parkinsonism, depletes stores of monoamine transmitters
What was the first specific antidepressant? what did it prove/ solidify?
Iproniazid (MAOI), monoamine hypothesis
What are the main classes of antidepressants which interfere with MA transmission?
SSRIs, tricyclics, MAOI, MA receptor antagonists
Give an examples of SSRI
Prozac- Fluoxetine
What are side effects of SSRIs?
Few BUT, nausea, diarrhoea, agitation, insomnia, anorgasmia, inhibit metabolism of other drugs
Give an example of TCAs?
Imiprimine
What are side effects of Imiprimine?
Sedation, anticholinergic- dry mouth, constipation, blurred vision, urinary retention, postural hypotension, seizures, impotence, CNS depressant
Give 2 examples of MAOs
Phenylzine- irreversible non competitive inhibitor and moclobemide- MAOa selective
Where is MAOa and MAOb found?
MAOa- CNS, MAOb-CNS and PNS
What are side effects of Phenylzine?
Cheese effect, hypotension, insomnia, weight gain, liver damage
What is the function of the Noradrenergic pathways in the CNS?
Pain, arousal, mood, blood pressure
What are drugs that specifically work on the reuptake of NA?
Reboxetine and Atomextine
Where are alpha 1 and alpha 2 NA receptors? What do they do?
Alpha 1- somatic dendritic region, increase 5HT. Alpha 2 - presynaptic, inhibit 5HT release
What are the functions of the seroternergic pathway in the CNS?
Hallucinations, sleep and wakefullness, mood and emotion, feeding behaviour, sensory pathways and nociception, body temperature, vomitting
What do drugs acting on 5HT treat?
Depression, anxiety migraine, anti-emetic (chemotherapy), antipsychotic
What is the cause of anhedonia?
5HT role in regulating limbic processing from normally pleasurable experiences
Why do SSRIs cause worse symptoms then better?
Weak activation of 5HT receptors causes less 5HT release than as more activation the inhibitory receptors become desensitised and the 5HT release increases
5HT regulates levels of BDNF, activation of 5HT receptors increases cAMP levels which also desensitises inhibitory receptors so are cAMP, PKA, CREW, BDNF
Where is low BDNF specifically observed?
In hippocampus
What other methods are used to treat bipolar?
Lithium, anti epileptic drugs, electroconvulsive therapy
How does Lithium treat bipolar?
Permeates Nav channels, inhibits inositol monophosphatase, AKT signalling and glycogen synthase kinase GSK3 signalling(involved in apoptosis)
What does electroconvulsive therapy do?
Downregulates B receptors and upregualtes 5HT2 sites. Downregulates 5HT1A sites
