Depression Flashcards
depression
mental disorder that impairs social/occupational functioning
14.4%
Limbic Brain
cortical barrier between brainstem and cortex
receives ascending information from spinal cord
amygdala
hippocampus
basal ganglia
cingulate gyrus
connections to frontal cortex + hypothalamus
fMRI
shows blood oxygen levels in brain
increase in blood-oxygen = increase in neuronal activity
MDD showed increase in limbic system activation and decrease in striatum activation
amine hypothesis
monoaminergic neurotransmitters: dopamine norepinephrine, serotonin
modulatory role - mood, arousal, attention
depression is the inadequate monoamine neurotransmission - less NT release, fewer receptors, impaired signal transduction
dopamine and NE
synthesis: tyrosine
catalysis: MAO
serotonin
synthesis: tryptophan
catalysis: MAO
reserpine
antihypertensive drug
depletes dopamine and NE neurons by blocking movement of dopamine into vesicle
causes depression-like syndrome
ipronazid
anti-tubercular drug
inhibits monoamine oxidase = increases synaptic concentration of monoamine NTs
alleviates depression
problem with amine hypothesis
drugs don’t work in everyone and only work ok
takes weeks to see clinical effects despite immediate effect in the synapse
glutamatergic hypothesis
depression is caused by reduced glutamatergic signalling in the cortex
decreased glutamate signalling impacts excitatory and inhibitory function
affects long-term potentiation, neurotrophic production, synapse formation, and gene transcription
monoamine targeting antidepressants
MAO inhibitors - block NT breakdown = higher levels in synapse
SSRIs and SNRIs - inhibit serotonin and NE transporters = higher levels in synapse
side effects = nausea, dizziness, weight loss
glutamate targeting antagonists
ketamine: non-competitve NMDA receptor antagonist
causes transient burst of glutamate from blocking of NMDA on GABA (can’t bind = build up) → reset of glutamate and GABA systems
narrow therapeutic window + intravenous administration
psychedelics
emerging therapy
study - blinding is impossible (placebo) + serious side effects
antidepressant effect by synaptic remodelling via intracelullar 5-HT2a receptors
lipophilic drug crosses membrane to stimulate population of receptors inside cortical neurons = neuronal growth