Chapter 6: Mood disorders Flashcards
DSM5 criteria for major depressive episode
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
DSM5 criteria for manic episode
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
definition of MDD
occurrence of at least 1 major depressive episode
definition bipolar 1
occurrence of at least 1 manic episode
definition bipolar 2
one+ major depressive episodes and at least one hypomanic episode
how can unipolar depression turn into bipolar depression
unipolar progresses to mixed symptoms which progresses to bipolar symptoms which progress to treatment resistance
non-euphoric manic symptoms
psychomotor agitation
impulsivity
irritability
racing thoughts
neurotransmitters involved in depression
norepinephrine, dopamine, serotonin, GABA, glutamate
how is norepinephrine synthesized
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
how is the action of norepinephrine terminated
reuptake into presynaptic neuron by NET
destroyed by enzymes
enzymes that destroy norepinephrine and whether they are intra or extracellular
MAO (A or B) intracellular (stored in mitochondria)
COMT - extracellular
what is the only norepinephrine receptor that can be a presynaptic autoreceptor
a2
where are a2 norepinephrine receptors and how do they work
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
what is the principal inhibitory neurotransmitter in the brain
GABA
how is GABA synthesized
GAD (glutamic acid decarboxylase) converts glutamate (amino acid) to GABA which is then transported into vesicles to await neurotransmission
vesicular transporter for GABA
VIAAT
how is the action of GABA terminated
reuptake by GAT
enzyme GABA transaminase converts GABA to an inactive substance
major postsynaptic GABA receptors and what type of receptors are they
GABA A - ligand-gated ion channel
GABA B - G protein-linked receptor
GABA C - ligand-gated ion channel
GABA A isoform subunits
a
β
γ
ẟ
ɛ
θ
π
action of benzodiazepine-sensitive receptors with a a1 subunit
good for sleep, sedative, hypnotic
action of benzodiazepine-sensitive receptors with a a2 subunit
good for anxiety
“other” GABA A receptor subtypes
synaptic
extrasynaptic
benzo-sensitive
benzo-insensitive
what is mediated by synaptic and extrasynaptic GABA A receptors
synaptic - phasic neurotransmission
extrasynaptic - tonic neurotransmission
are benzodiazepines PAMs or NAMs
what has to be present for it to work
GABA A PAMs
GABA must be present
what counteracts benzodiazepine action
flumazenil
selectivity of currently available benzodiazepines
non-selective for GABA A receptors with different a subunits
location of benzodiazepine sensitive/insensitive GABA A receptors
sensitive - postsynaptic
insensitive - extrasynaptic
monoamine hypothesis of depression
depression is d/t a deficiency in monoamine neurotransmission
evidence is lacking for this theory
monoamine receptor hypothesis of depression
depletion of neurotransmitter causes compensatory upregulation of postsynaptic receptors and this leads to depression
if medications cause neurotransmitters to rise immediately, why does it take so long to see clinical effectiveness - hypothetically
it takes awhile for the downregulation of receptors to occur
it takes awhile for downstream synthesis of growth factors (BDNF)
what is the main function of BDNF
promote growth/development of immature neurons
enhance survival/function of adult neurons
help maintain synaptic connections
what are a few things that may lead to neuronal cell loss
decreased BDNF
HPA axis dysregulation
neuroinflammation
what is the relationship between monoamines and BDNF availability
monoamines can induce signal transduction cascades that lead to the release of BDNF
how does dysregulation of the HPA axis lead to depression
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
how does neuroinflammation lead to loss of synapses and cell death
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
measurements of circadian rhythm that are altered in depression
-flattening of daily body-temp cycle
-elevated cortisol secretion in the day
-decreased melatonin secretion at night
-reduction in BDNF and neurogenesis
what is one of the most common residual symptoms of depression
cognitive dysfunction
diffuse dopamine dysfunction drives what type of depressive symptoms
symptoms r/t reduction of positive affect
diffuse serotonin dysfunction drives what type of depressive symptoms
increase in negative affect
what depressive symptoms are mediated by the PFC
-concentration/interest/pleasure
-mental fatigue
-guilt, suicidality, worthlessness
-mood
what depressive symptoms are mediated by the striatum
-mental fatigue
-pleasure/interests
-fatigue/energy
what depressive symptoms are mediated by the hypothalamus
sleep
appetite
what depressive symptoms are mediated by the amygdala
guilt
suicidality
worthlessness
what depressive symptoms are mediated by the spinal cord
physical fatigue
depressive symptoms mediated by the cerebellum
psychomotor
manic symptoms mediated by the PFC
-racing thoughts
-grandiosity
-distractibility
-pressure speech
-mood
-risk-taking
manic symptoms mediated by the basal forebrain
decreased need for sleep
increased arousal
manic symptoms mediated by the striatum
-racing thoughts
-grandiosity
-increased goal-directed behavior
-motor agitation
manic symptoms mediated by the thalamus
decreased need for sleep
increased arousal
manic symptoms mediated by the hypothalamus
decreased need for sleep
increased arousal
manic symptoms mediated by the amygdala
mood
