Neurobiology of Depression- Craviso Flashcards
What areas of the brain are involved with regulation of mood and emotion expression, reward processing, attention, motivation, stress response, and neuro-vegetative function?
- hypothalamus
- hippocampus
- cingulate gyrus
- amygdala
- prefrontal cortex
- ventral striatum
What makes up the limbic system?
Hippocampus
Hypothalamus
Amygdala
Is the a diagnostic blood or brain test for depression?
no
What are some neuro-imaging techniques to check for depression (not diagnosis it)?
PET-check brain blood flow, tissue metabolis, biochemical activity
MRI- spatial images of brain
In depressed patients what happend to their gray matter?
In depressed patients what happened to their cell counts and cell markers?
decreased in hippocampus, cingulate gyrus, amygdala, prefrontal cortex, ventral striatum
In addition to decreased gray matter volume and cell counts, what else do depressed patients have decreased amounts of?
-reduced number of synapses and gial cells, reduced neuronal size
In depressed peope their is an increase in (Blank) especially in the orbital and medial prefrontal cortex and the amygdala.
blood flow
Where do you see an abnormality in the brain of depressed patients and correlates positively with depression severity?
anterior cingulate cortex subgenual area
In major depression and even in response to scripts that induce transient sadness you will see increased activity in the (BlanK) but activity will return to normal with successful pharm treatment
ACC (anterior cingulate cortex)
In depressed patients, did they have elevated or depressed metabolism in the rostral anterior cingulate cortex?
Is it better or worse to have more metabolic activity?
elevated
better-> indicates better response to treatment
What did reserpine, a blood pressure med, also do?
induce depression
What did iproniazid, a drug used to treat TB, also do?
induce signif mood-elevation
How does reserpine work?
inhibits vesicular storage of biogenic amines (NE, dopamine serotonin) resuting in their metabolism by monoamine oxidase.
I.e got rid of NE, dopamine and 5HT
What is the major consequence of reserpine?
depletes neuronal stores of biogenic amines
What does iproniazid do?
inhibits intraneuronal monoamine oxidase
What is the consequence of iproniazid?
increase levels of biogenic amines
What is the monoamine hypothesis of depression?
depression viewe as a deficit of biogenic monoamines (particularly norepinephrine and serotonin)
Where does the serotonergic system begin and where does it project to?
raphe nuclei-> project to the cortices, cerebellar cortex, limbic system, spinal cord, nucleus accumbens, neocortex, cingulate gyrus, deep cerebellar nuclei
Where does the noradrenergic system begin and where does it project to?
locus ceruleus and lateral tegmental NA cell system-> project to thalamus, cingulat gyrus, limbic system, neocortex, cerebellar cotex, spinal cord
Is the monoamine hypothesis of depression accurate?
sort of, it is too simplistic … a single drug cannot restore balance among all the interacting neuronal networks involved… this is proved by the delayed effects of antidepressants
About (blank) percent of patients respond in the short-term to antidepressants; total remission of systoms around (blank)
60-70%
50%
So why do antidepressants work if they monoamine hypothesis isnt accurate?
because the antidepressants eventally change the structure of the CNS make new synapses and such which is what treats the patient… i,e its what the monoamines can do, not the lack of the monoamines themselves.
Most clinicaly used antidepressant drugs rapidly increase (Blank) levels whereas therapeutic effects are delayed by (blanK)
biogenic amine
several weeks
What are antidepressant effects likely due to?
adaptive changes in the CNS that take time to develop
What are the adaptive changes identified with antidepressants that increase biogenic monoamines?
long-term enhancement of monoamine neurotransmission
What is the long-term enhancement of monoamine transmission due to?
- desensitization of autoreceptors on monamine nerve terminals (reduces negative feedback and therefore increases release of monoamines)
- increased activity of certain post-synaptic monoamine receptors
What is the neurotrophic hypothesis of depression?
depression is associated w/ loss of neurotrophic support
How do you treat depression if you believe in the neurotrophic hypothesis?
antidepressant that increase neurogenesis and synaptic connectivity in cortical areas such as the hippocampus (neural plasticity/ changes in neural network connectivity)
What can antidepressants do other than increase biogenic amine levels?
cause an increase in nerve growth factor expression (i.e BDNF)-> critical in regulation of neural plasticity, resilience and neurogenesis
What does increasing BDNF result in?
long term adaptive changes that result in synaptogenesis
T or F
Depression and stress are interrelated
Which hypothesis does this support?
T
neurotrophic hypothesis
How is stress and depression related?
stress results in increased cortisol levels which results in atrophy of neurons in the hippocampus
Chronic stress decreases (blank)
BDNF
In a depressed state, you will have increased glucocorticoids that will inhibit (blank) and result in decrease synaptogenesis and result in neuron atrophy
BDNF
In the treated state of depression you have increase in (Blank) inducing synaptogenesis.
BDNF
What does LTP do?
increases sensitivity of post-synaptic neurons to glutamate-> eventually results in synaptogenesis
How can you speed of synaptogenesis?
with electro therapy
GABA B presynpatically gets bound by Gaba and (blank) calcium influx which results in decreased release of GABA
decreases
What do the GABA receptors do postsynaptically
Postsynaptically GABA B receptors will bind GABA and let potassium out or reduce calcium influx and hyperpolarize membrane along with GABA A which will give Cl- ions to hyperpolarize membrane.
What drug can super fast speed up synaptogenesis?
ketamine
How does ketamine work?
in mysterious ways, it is an NMDA glutamate receptor antagonist that somehow increases glutamate neurotransmission
A single dose of ketmine delivered via IV infusion alleviated depressive symptoms within (Blank)
hours
Ketamine reduced (blank) ideation
suicidal
Ketamine was found to be effective for patients who failed to respond to (blank) or more conventional antidepressants (refractory depression)
2
Ketamine is effective for (blank) disorder
bipolar
How long do the effects of ketamine last?
days to weeks
WHere does ketamine bind in the NMDA receptor?
inside and works as an antagonist
What are the clinical manifestations of ketamine use?
dissociative symptoms and anesthesia
SOOO how ketamine promote synaptogenesis if it is a NMDA inhibitor?
dont really know, proposed to rapidly and transiently increase glutamate neurotransmission, possibly by inhibition of tonically active GABA-ergic interneurons
Ketamine has an LTP-like effect due to a rapid increase in (blank) levels and (blank) receptors
BDNF
AMPA
Ketamine rapidly causes (blank)
synaptogenesis
How should you give ketamine and why?
IV cuz it has poor bioavailability when taken orally.
Ketamine needs to be researched more and does have some potential for abuse but its positive effects on (Blank) has had a meaningful impact on the future development of novel therapeutics for depression
depression
Mental disorders are (blank) disorders- so less specific neurotransmitters, more about synaptogenesis and neuroplasticity.
circuit
What is the non-pharmacological way to treat depression and induce synaptogenesis?
Deep brain stimulation
What is deep brain stimulation?
electric stimulation “quiets” the overactive region-alters excitability by affecting neural networks (synaptogenesis/neural plasticity)
What is ECT?
intentionally triggers a brief seizure
Why does DBS only work for a small amount of time?
because as the natural progression of the disease continues you lose neurons to perform DBS on
DBS is approved by the FDA to treat severe (blank)
OCD
What is in clinical trials to assess other ways of stimulation to treat depression?
transcranial magnetic stimulation (TMS) -non-invasive
