Lecture 25 - Antidepressants

Question 1

a recurring and debilitating mental disorder that impairs social and/or occupational functioning

Answer 1

depression

Question 2

subjective feelings regulated by the limbic system

Answer 2

emotions

Question 3

behaviour that is purposeful and goal directed and is regulated by the mesocorticolimbic dopamine system

Answer 3

motivation

Question 4

an evolutionarily ‘old’ neocortex that includes the amygdala, hippocampus, basal ganglia, and cingulate gyrus with connections to the frontal cortex and hypothalamus

Answer 4

the limbic brain

Question 5

major depressive disorder is associated with increased engagement of ____ and decreased engagement of ____ compared to healthy controls

Answer 5

limbic regions (amygdala), regions involving motivation (striatum)

Question 6

changes in brain activity reflect changes in:

Answer 6

neurotransmitter release and/or postsynaptic response

Question 7

dopamine, norepinephrine, and serotonin are collectively known as the:

Answer 7

monoaminergic neurotransmitters

Question 8

have a ‘modulatory’ role in the brain, and are involved in mood, arousal, and attention

Answer 8

monoamineergic neurotransmitters

Question 9

what is the amine hypothesis of depression

Answer 9

alterations in the monoaminergic neurotransmitters are associated with mood disorders

Question 10

depression is associated with inadequate monoamine neurotransmission in the brain. this may be due to:

Answer 10

• less neurotransmitter release
• fewer receptors
• impaired signal transduction

Question 11

where did the amine hypothesis of depression originate?

Answer 11

from observations that manipulation of the monoaminergic system influences depression symptoms

Question 12

15% of patients who receive long term treatment with the antihypertensive drug ______ developed a syndrome indistinguishable from naturally occuring depression

Answer 12

reserpine

Question 13

what does reserpine do?

Answer 13

depletes neurons of dopamine and norepinephrine transmitters

Question 14

in the 1950s, it was noted that the anti-tubercular drug, ______, alleviated depression

Answer 14

ipronazid

Question 15

what does ipronazid do?

Answer 15

inhibits monoamine oxidase (MAO)

Question 16

what are the three major issue with the amine hypothesis of depression?

Answer 16

• drugs that restore monoamineric levels are only moderately effective in 30-50% of patients
• inconclusive evidence that serotonin and noradrenergic systems are disrupted in depression
• antidepressants take several weeks before a clinical effect is seen

Question 17

what is the glutamatergic hypothesis of depression?

Answer 17

depression is associated with a reduction of glutamatergic signalling in the cortex

Question 18

a loss of glutamatergic signalling impacts both excitatory and inhibitory functions leading to:

Answer 18

reduced signal to noise

Question 19

monoamine antidepressants increase synaptic levels of:

Answer 19

monoamine neurotransmitters (particularly norepinephrine and serotonin)

Question 20

an enzyme involved in the breakdown of amine neurotransmitters (serotonin, noradrenaline, and dopamine)

Answer 20

monoamine oxidase (MAO)

Question 21

what is the effect of blocking amine neurotransmitter breakdown?

Answer 21

increase synaptic levels of amine neurotransmitters and can improve mood

Question 22

what is an example of a monoamine oxidase (MAO) inhibitor?

Answer 22

ipronazid

Question 23

why must monoamine oxidase (MAO) inhibitors taken with a low tyramine diet?

Answer 23

to avoid the “tyramine cheese reaction”

Question 24

a sympathomimetic monoamine that acts like noradrenaline, is found naturally in aged cheese, and is degraded by monoamine oxidase (MAO)

Answer 24

tyramine

Question 25

eating a meal rich in tyramine while taking a monoamine oxidase (MAO) inhibitor can lead to _____ caused by tyramine binding to _____ on the blood vessels and in the heart

Answer 25

acute hypertension reactions, adrenergic receptors

Question 26

what do selective reuptake inhibitors do?

Answer 26

inhibits the serotonin (SERT) or noradrenaline transporters (NET) which move the neurotransmitter from the synapse to the intracellular space

Question 27

blocking transporters increases the extracellular concentration of:

Answer 27

neurotransmitters

Question 28

drugs that are selective for serotonin transporters (SERT) are called:

Answer 28

selective serotonin reuptake inhibitors (SSRIs)

Question 29

drugs that inhibit both serotonin transporters (SERT) and norepinephrine transporters (NET) are called:

Answer 29

serotonin norepinephrine reuptake inhibitors (SNRIs)

Question 30

what is an example of an SSRI?

Answer 30

fluoxetine (prozac)

Question 31

how effective are drugs that restore monoaminergic levels in patients with depression?

Answer 31

only moderately effective in 30-50% of patients

Question 32

how long does is take for a clinical effect to be seen when taking MAOIs, SSRIs, and/or SNRIs?

Answer 32

takes several weeks (despite immediate effects on synaptic neurotransmitter levels)

Question 33

what are some common side effects of taking MAOIs, SSRIs, and/or SNRIs?

Answer 33

nausea, indegestion, dizziness, dry mouth, weight loss, etc

Question 34

consciuous states (our thoughts, emotions, and experiences) emerge not from individual brain regions or neurotransmitters, but from:

Answer 34

coordinated activity across a network

Question 35

mood disorders are a result of:

Answer 35

inappropriate coupling between brain regions

Question 36

conscious states are a(n) ______ of the brain

Answer 36

'emergent property' (cannot be wholly explained by their individual parts)

Question 37

true or false: drugs that disrupt or reset neuronal activity on a global scale may be effective at treating depression

Answer 37

true

Question 38

what is ketamine?

Answer 38

a noncompetitive NMDA receptor antagonist that acts as a dissociative anesthetic with halluconigenic properties

Question 39

ketamine has recently been shown to have potential as an:

Answer 39

antidepressant medication

Question 40

depression is associated with a reduction in _____ in the cortex

Answer 40

glutamatergic signalling

Question 41

ketamine causes a transient burst in _____ resulting from blockage of NMDA receptors on _____

Answer 41

glutamate, GABA interneurons

Question 42

the supposed 'glutamate burst' from ketamine causes:

Answer 42

synaptic remodelling and resetting of glutamate and GABA systems

Question 43

can ketamine have long term effects due to other downstream signalling effects (ex: BDNF release, gene transcription)?

Answer 43

yes

Question 44

what are the limitations of using ketamine as an antidepressant?

Answer 44

- very narrow therapeutic index - must be administered intravenously in a hospital setting

Question 45

true or false: there is emerging evidence that classical psychedelics can improve symptoms of depression

Answer 45

true

Question 46

a recent high quality study shows that two doses of _____ improves mental health significantly better than SSRIs

Answer 46

psilocybin

Question 47

what are the caveats to studies involving psychedelic treatment of depression?

Answer 47

- blinding is nearly impossible (results may reflect placebo) - may have serious side effects (ie: suicidal ideation, anxiety, negative trips)

Question 48

emerging evidence shows that psychedelics (and SSRIs) bind to the _____ receptor, which initiates _____ to "reset" cortical networks

Answer 48

BDNF, neuroplasticity