Mood Disorders Flashcards
(45 cards)
How does ketamine exert its antidepressant actions and who said this?
Ketamine is an NMAR antagonist on the GABA interneurone leading to more inhibition of GABA- less GABA release causing less inhibition of the main neurone and so increase in glutamaterelease leading to anti-depressant effects
Aleksanra et al 2017
How else apart from NMDAR antagonism does ketamine exert its anti-depressant effects
Zanos et al showed least amount of escape failures in mouse model with the ketamine metabolite HNK
It is seen to enhance hippocampal fEPSP
Describe the antidepressant actions of tianeptine
In the force swim test samuels et al 2017 found that mouse administered with tianpetine compared to saline spent the lest amount of time immobile
Apart from antiepressant actions what else does tianeptine do?
enhances place recognition memory in mice
enhances hippocampal AMPA receptor dependent synaptic transmission and enhances hippocampal long term potentiation of synaptic strength
What does the tianeptine work on?
the mu and delta opiod receptors and particularly its actions of the delta opiod receptors may underlie its AMPA-modulating properties
Name the different inputs to the nucleus accumbens
medial pre-frontal cortex
basolateral amygdala
ventral tegmentum
hippocampus
Discuss D1and D2 expressing medium spiny neurons
D1 MSN activation reinforces behaviour an is rewarding
D2 MSN- activation inhibits behaviour an is aversive
What does Francis et al say about D1 MSN?
repeated d1 MSN activation reverses the social interaction imapirement
What does covington et al say?
Says that IEG(immediate early genes) markers of neuronal activity are reduced in post mortem brain tissue from depressed patients
Reduced in mouse social defeat stress model of depression
Rescuing depressant affects?
optogenetic burst activation of the mPFC has antidepressant effects
What does Johnston et al say?
Hippocampal activity is abnormally high during loss events in treatment resistant depression
Talk about the optogenetic dissection of the roles of hippocampal versus prefrontal inputs
optogeneti depression of synaptic strength in the hippocampal —-Nac pathway reverses chronic social defeat stress induced depressive symptoms
optogenetic stimulation of vHPC–NAc increases depressive symptoms
optogeneti stimulation of mPFC—NAc decreases the depressive symptoms
Induction of LTD at vHIP—NAc synapses reverses depressive symptoms
Bagot et al 2015
Stats on depression stuff
Whitford et al 2010 says that mental and substance use disorders are the leading cause of years lived with disability
Chang C et al 2011- according to a london based study 32,000 people - 8-15years lost for men and 10-18 lost for women
What is the ICD-10 criteria for depression?
2 out of - depressed mood - loss of interest/anhydonia - anergia \+
3 out of
- reduced concentration
- decreased self esteem
- guilt/unworthiness
- disturbed sleep/appetite
For atleast 2 weeks
Talk about RDoc and the National Institue of Mental Health
RDoc- framework of priorities that the NIMH will fund
the domains are
- negative valence- fear, anxiety, loss etc
- positive valence- reward, habituation, values
- cognitive system- attention, memory
- social system- attachment, communication
-arousal/modulatory- circadian rhythm, sleep/wake cycle
Discuss the disordered appetitive with relation to depression and mania?
previously neutral stimuli becomes rewarding- mania
difficulty identifiying rewarding stimuli , reduced sontact with previously rewarding stimuli and increased aversive stimuli contact—low mood
what does porter et al 2003 say?
severity of depression correlates with impairement in learning and memory
What did the study by johnston et al 2015 show?
failure of hippocampal deactivation during loss events in depression
abnormal hippocampal activity correlates well with severity of cognitive features of depression
Dorsal raphe nucleus- overactive
median raphe nucleus- underactive resulting in overactive hippocampus during loss events
success/reward gan events- blunted striatal pathway
Who talks about increased amygdala activation in depression?
Drevets 1997
What does schmall et al say?
meta analysis - of roughly 9,000 participants , enigma group using neuroimaging showed robust reduction in hippocampal volume
how is the ventral striatum affected in depression?
blunted striatal reward link activation - blunted positive valance system
What did devinski 1999 say?
regions implicated in depression- anterior cingulate and used to be a long establishe treatment only for severe highly resistant depression, involves small bilateral lesions placed in cingulate bundle
What did steele 2008 discover?
basically anterior cingulate gyrus has been implicated in depression especially the more rostral parts
placing a lesion there will help with depression
Discuss the median raphe nucleus and dorsal raphe nucleus
Median raphe nucleus- inhibits consolidation of aversive memories via hippocampus and this is underactive in depression thus causing ruminations
