Chapter 6: Mood disorders

Question 1

DSM5 criteria for major depressive episode

Answer 1

depressed mood or apathy and at least 4 of the following:
weight/appetite changes
sleep disturbance
psychomotor agitation/retardation
fatigue
feelings of guilt/worthlessness
suicidal ideation

Question 2

DSM5 criteria for manic episode

Answer 2

elevated or irritable mood and at least 3 of the following:
grandiosity
increased goal-directed activity
risk-taking
decreased need for sleep
easily distracted
talkative/pressured speech
flight of ideas/racing thoughts

Question 3

definition of MDD

Answer 3

occurrence of at least 1 major depressive episode

Question 4

definition bipolar 1

Answer 4

occurrence of at least 1 manic episode

Question 5

definition bipolar 2

Answer 5

one+ major depressive episodes and at least one hypomanic episode

Question 6

how can unipolar depression turn into bipolar depression

Answer 6

unipolar progresses to mixed symptoms which progresses to bipolar symptoms which progress to treatment resistance

Question 7

non-euphoric manic symptoms

Answer 7

psychomotor agitation
impulsivity
irritability
racing thoughts

Question 8

neurotransmitters involved in depression

Answer 8

norepinephrine, dopamine, serotonin, GABA, glutamate

Question 9

how is norepinephrine synthesized

Answer 9

tyrosine is transported from blood into brain where tyrosine hydroxylase (TOH) coverts it to DOPA which is then converted into dopamine by DOPA decarboxylase (DDC). Dopamine is converted into norepinephrine by dopamine β-hydroxylase (DBH), which is then packed into synaptic vesicles to await neurotransmission

Question 10

how is the action of norepinephrine terminated

Answer 10

reuptake into presynaptic neuron by NET
destroyed by enzymes

Question 11

enzymes that destroy norepinephrine and whether they are intra or extracellular

Answer 11

MAO (A or B) intracellular (stored in mitochondria)
COMT - extracellular

Question 12

what is the only norepinephrine receptor that can be a presynaptic autoreceptor

Answer 12

a2

Question 13

where are a2 norepinephrine receptors and how do they work

Answer 13

axonic - allows norepinephrine release when not bound by monoamine
somatodendritic - when norepinephrine binds to receptor it shuts off neuronal impulse flow which stops the release of the neurotransmitter

Question 14

what is the principal inhibitory neurotransmitter in the brain

Answer 14

GABA

Question 15

how is GABA synthesized

Answer 15

GAD (glutamic acid decarboxylase) converts glutamate (amino acid) to GABA which is then transported into vesicles to await neurotransmission

Question 16

vesicular transporter for GABA

Answer 16

VIAAT

Question 17

how is the action of GABA terminated

Answer 17

reuptake by GAT
enzyme GABA transaminase converts GABA to an inactive substance

Question 18

major postsynaptic GABA receptors and what type of receptors are they

Answer 18

GABA A - ligand-gated ion channel
GABA B - G protein-linked receptor
GABA C - ligand-gated ion channel

Question 19

GABA A isoform subunits

Answer 19

a
β
γ
ẟ
ɛ
θ
π

Question 20

action of benzodiazepine-sensitive receptors with a a1 subunit

Answer 20

good for sleep, sedative, hypnotic

Question 21

action of benzodiazepine-sensitive receptors with a a2 subunit

Answer 21

good for anxiety

Question 22

“other” GABA A receptor subtypes

Answer 22

synaptic
extrasynaptic
benzo-sensitive
benzo-insensitive

Question 23

what is mediated by synaptic and extrasynaptic GABA A receptors

Answer 23

synaptic - phasic neurotransmission
extrasynaptic - tonic neurotransmission

Question 24

are benzodiazepines PAMs or NAMs
what has to be present for it to work

Answer 24

GABA A PAMs
GABA must be present

Question 25

what counteracts benzodiazepine action

Answer 25

flumazenil

Question 26

selectivity of currently available benzodiazepines

Answer 26

non-selective for GABA A receptors with different a subunits

Question 27

location of benzodiazepine sensitive/insensitive GABA A receptors

Answer 27

sensitive - postsynaptic insensitive - extrasynaptic

Question 28

monoamine hypothesis of depression

Answer 28

depression is d/t a deficiency in monoamine neurotransmission evidence is lacking for this theory

Question 29

monoamine receptor hypothesis of depression

Answer 29

depletion of neurotransmitter causes compensatory upregulation of postsynaptic receptors and this leads to depression

Question 30

if medications cause neurotransmitters to rise immediately, why does it take so long to see clinical effectiveness - hypothetically

Answer 30

it takes awhile for the downregulation of receptors to occur it takes awhile for downstream synthesis of growth factors (BDNF)

Question 31

what is the main function of BDNF

Answer 31

promote growth/development of immature neurons enhance survival/function of adult neurons help maintain synaptic connections

Question 32

what are a few things that may lead to neuronal cell loss

Answer 32

decreased BDNF HPA axis dysregulation neuroinflammation

Question 33

what is the relationship between monoamines and BDNF availability

Answer 33

monoamines can induce signal transduction cascades that lead to the release of BDNF

Question 34

how does dysregulation of the HPA axis lead to depression

Answer 34

when stress causes neurons in the hippocampus to atrophy they no longer inhibit the HPA axis so it becomes overactive leading to elevated levels of glucocorticoid and insensitivity to feedback inhibition

Question 35

how does neuroinflammation lead to loss of synapses and cell death

Answer 35

inflammation activates microglia in the brain to release proinflammatory molecules that attract immune cells which disrupts neurotransmission and causes oxidative stress, mitochondrial dysfunction, HPA axis dysfunction, reduction of neurotrophic factor availability, and epigenetic changes to unwanted gene expression which leads to synapse loss and cell death

Question 36

measurements of circadian rhythm that are altered in depression

Answer 36

-flattening of daily body-temp cycle -elevated cortisol secretion in the day -decreased melatonin secretion at night -reduction in BDNF and neurogenesis

Question 37

what is one of the most common residual symptoms of depression

Answer 37

cognitive dysfunction

Question 38

diffuse dopamine dysfunction drives what type of depressive symptoms

Answer 38

symptoms r/t reduction of positive affect

Question 39

diffuse serotonin dysfunction drives what type of depressive symptoms

Answer 39

increase in negative affect

Question 40

what depressive symptoms are mediated by the PFC

Answer 40

-concentration/interest/pleasure -mental fatigue -guilt, suicidality, worthlessness -mood

Question 41

what depressive symptoms are mediated by the striatum

Answer 41

-mental fatigue -pleasure/interests -fatigue/energy

Question 42

what depressive symptoms are mediated by the hypothalamus

Answer 42

sleep appetite

Question 43

what depressive symptoms are mediated by the amygdala

Answer 43

guilt suicidality worthlessness

Question 44

what depressive symptoms are mediated by the spinal cord

Answer 44

physical fatigue

Question 45

depressive symptoms mediated by the cerebellum

Answer 45

psychomotor

Question 46

manic symptoms mediated by the PFC

Answer 46

-racing thoughts -grandiosity -distractibility -pressure speech -mood -risk-taking

Question 47

manic symptoms mediated by the basal forebrain

Answer 47

decreased need for sleep increased arousal

Question 48

manic symptoms mediated by the striatum

Answer 48

-racing thoughts -grandiosity -increased goal-directed behavior -motor agitation

Question 49

manic symptoms mediated by the thalamus

Answer 49

decreased need for sleep increased arousal

Question 50

manic symptoms mediated by the hypothalamus

Answer 50

decreased need for sleep increased arousal

Question 51

manic symptoms mediated by the amygdala

Answer 51

mood