depression pathophysiology Flashcards
what are the 5 theories for the aetiology of depression
monoamine
neuroendocrine
inflammatory
structural
neoplasticity and neurogenesis
what is the monoamine theory of depression
functional deficit of monoamine neurotransmitters in the brain
what is the evidence for the monoamine theory for depression
TCAs - block monoamine uptake and enhance mood
methyldopa - inhibits NA synthesis and reduces mood
what is the neuroendocrine theory for depression
increased cortisol levels, impaired glucocorticoid induced feedback control
CRH injection mimics depression
what are the inflammatory mechanisms theory of depression
cytokines can cause behavioural changes and depressive moods - IL2 and IF-gamma
what is the theory for structural changes in depression
neuronal cell loss, decrease in grey matter volume in pre-frontal cortex and hippocampus
what is the neurogenesis theory for depression
BDNF controls neurogenesis , less BDNF = less devlopment = depression
how does stress lead to depression
release of glutamate = excitotoxicity = neuronal cell death
what are the the drug targets for treating depression
SERT and NET
what is SERT
serotonin reuptake transporter
12 transmembrane domains
C and N termini intracellular
Substrate binding is external or internal
what are the acute consequences of acute increased 5HT
increased synaptic serotonin - binds to 5HT1A to inhibit serotonin release
what are the effects of chronic raised 5HT
prolonged serotonin release induces 5HT1A desensitisation
what role does NA play in the release of 5HT
acts on excitatory alpha 1 to enhance serotonin release
alpha 2 receptors downregulated by antidepressants - antagonists can enhance 5HT release (mirtazapine)
what are the 7 types of serotonin receptors
1A-E - G alpha i
2A-C - G alpha Q
4-7 - G alpha S
what are monoamine inhibitors
inhibits MAO to inhibit neurotransmitter breakdown - so more NA/5HT in nerve terminals
