25 - Depression Flashcards
(17 cards)
How many out of 9 symptoms in a 2 week period do you need to be diagnosed with depression?
5
What is emotion?
subjective feelings (anger, fear, sadness, jealousy) - Limbic system
What is motivation?
Behaviour that is purposeful and goal directed - Mesocortiolimbic dopamine system
What is the limbic brain?
Cortical border circling the brainstem
includes amygdala (emotion), hippocampus, basal ganglia, cingulate gyrus with connections to the frontal cortex and hypothalamus
Major depression disorder is associated with:
increased engagement of limbic regions (amygdala) and decreased engagement of regions involved in motivation (striatum) compared to healthy controls
What is the amine hypothesis of depression?
depression is associated with inadequate monoaminergic neurotransmission (dopamine, norepinephrine, serotonin)
Explain ipronazid
It was discovered that ipronazid alleviated depression in 1950. But it was later discovered that this drug inhibited monoamine oxidase (MAO) the enzyme responsible for the breakdown of monoamines. This led to increased synaptic concentration of monoamine neurotransmitters
What is the glutamatergic hypothesis of depression?
Depression associated with reduction glutamatergic signaling in the cortex. Loss of glutamatergic signaling impacts both excitatory and inhibitory function leading to reduced signal to noise
Loss of glutamatergic signaling also impacts long-term potentiation, neurotropic production (BDNF (neuron synthesis and growth)), synapse formation, gene transcription (brain remodeling)
What is the issue with reserpine?
It is a antihypertensive drug. 15% of people who took reserpine developed a syndrome indistinguishable from naturally occurring depression
Reserpine depletes neurons of dopamine and norepinephrine transmitters
How do MAO inhibitors work?
increase synaptic levels of monoamine NT (particularly norepinephrine and serotonin)
MAO is an enzyme involved in breakdown of amine NT
these drugs must be taken with a low tyramine diet to avoid tyramine cheese reaction
What is tyramine?
naturally found in certain foods, such as aged cheese
What can eating a meal rich in tyramine while taking a MAO inhibitor cause?
Acute hypertension reaction caused by tyramine binding to adrenergic receptors on blood vessels and in the heart AVOID TYRAMINE CHEESE REACTION
SERT: serotonin
NET: noradrenaline transporters
What do transporters do?
What are drug selective for SERT called? What are drugs that inhibit both NET and SET called?
Move NT from synapse to intracellular space.
selective serotonin reuptake inhibitors (SSRIs)
serotonin norepinephrine reuptake inhibitors (SNRI)
SSRI and SNRI are GOOD
SSRI good for serotonin
SNRI good for serotonin and noradrenaline
What are limitation of MAO antidepressants?
drugs that restore monoaminergic levels are moderately effect
MAOIs, SSRIs, and SNRIs take several seeks before clinical effect is seen, despite immediate effects on synaptic NT levels
MAOIs, SSRIs, and SNRIs affect serotonin and noradrenaline levels throughout the body. This leads to side effects such as nausea, indigestion, dizziness, dry mouth, weight loss, etc.
What is ketamine?
Glutamate antidepressant
INCREASINGS BDNF
noncompetitive NMDA receptor antagonist on GABA interneuron
dissociative anesthetic with hallucinogenic properties
recently been demonstrated to have potential as an anti-depressant medication
Describe Depression and Ketamine
Depression is associated with reduction in glutamatergic signaling in the cortex.
Ketamine causes a transient burst in glutamate (resulting from blockage of NMDA receptors on GABA interneurons)
glutamate causes synaptic remodeling and resetting of glutamate and GABA systems
PROBLEM: narrow therapeutic index
Can classical psychedelics improve symptoms of depression?
yes
bind to TRKB (BDNF receptor, increases neuron synthesis)
