6 - Depression Flashcards by Maisie Lygo

what is the correct term for a sustained period of depression?

major depressive episode

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MDEs are seen principally in what 3 psychiatric diagnoses?

major depressive disorder
bipolar disorder
schizophrenia

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what questionnaire can help diagnose MDE?

patient health questionnaire (PHQ-9)

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what are the diagnostic criteria for MDE?

5 or more in same 2 week period that represent change from normal:
* anhedonia or depressed mood - MUST
* causes significant distress/impairment of function
* not part of bipolar
* not due to direct physiological effects of substances
* not better acocunted for by bereavement

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what are somatic delusions?

fixed false beleifs about pts body, eg. “my body is rotting/hollow/empty”

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depression is the leading cause of disability in both males and females. who is the burden of depression higher in?

burden of depression is 50% higher in females than males
leading cause of burden in females in high-, middle-, and low-income contries

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what are the two types of monoamines relevant in depression?

Noadrenaline - catecholamine
serotonin - indoleamines

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what is the general structure of catecholamines?

benzene ring
2 hydroxyl side groups
amine chain

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what is the general structure of indoleamines?

bicyclic ring of benzene
fused with pyrrole
amine side chain

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how is noradrenaline synthesised?

tyrosine
hydolysed by tyrosine hydroxylase (TH) into dopamine
decarboxylysed by DBH (dopamine beta-hydroxylase) into noradrenaline

methyl group added = adrenaline

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how is serotonin synthesised?

tryptophan
hydryolysed by tyrptophan hydroylase into 5-hydroxytryptophan
converted into 5-HT by L-AADC

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what is tyrosine?

non-essential large neutral amino acid (LNAA)

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how is tyrosine transported across the blood brain barrier?

active transport

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where is tyrosine converted into NAdr?

neuronal cell bodies in pons
particularly locus ceruleus

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what is tryptophan?

dietary essential, large neutral amino acid (LNAA)

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where is tryptophan converted into 5-HT?

neuronal cell bodies in raphe nuclei (chain of brainstem nuclei)
particularly dorsal and medial raphe

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how are the signals of 5-HT terminated?

5-HT reuptake transporter (SERT)
monoamine oxidase (MAO-A) degrades 5-HT in synapse and also some that has been reuptaken

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how are NAdr signals terminated?

NAdr reuptake transporter
MAO-A
COMT (catechol-O-methyl transferase

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describe the enzymatic degradation of 5HT?

broken down by monoamine oxidase
into 5-HIAA (hydroxyindole acetic acid)

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describe the enzymatic degradation of NAdr?

MAO and COMT degrade it
into vanillylmandelic acid and 3-methoxy-4-hydroxy-phenylglycol

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what are the 3 types of adrenergic receptors that NAdr acts on?

alpha1
M2
N1-3

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which noradrenergic receptor is most relevant to depression?

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which 5-HT receptor in the only one that isn’t coupled with a G-protein?

5-HT3 - ligand gated ion channel

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serotonin stimulate nuronal firing at all 5HT receptors, apart from which 2?

5HT1 and 5HT5

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NAdr stimulation at alpha2 auto and heteroreceptors on NAdr and 5HT neurons result in what?

* decreased cell firing * reducing serotonin release

NAdr stimulation at alpha1 adreno-heteroreceptors on 5HT cell bodies result in what?

increased 5HT cell firing

how does NAdr regulate serotonin?

* NAdr released from cell body and binds to receptors * if alpha2 auto or hetero on NAdr/5HT neuron, decreases cell firing and 5HT release * if alpha 1 adrenoreceptor on 5HT cell body, increased 5HT release

drugs that deplete monoamines cause what?

depression

antidepressants increase what neurotransmitters?

5HT and NAdr

what was the first anti-depressant?

* iproniazid (developed for TB) * monoamine oxidase inhibitor

give an example of a VMAT blocker that causes depression as a side effect?

* reserpine * antihypertensive +antipsychotic in 50s * depletes MOA by blocking VMAT

what does VMAT stand for?

vesicular monoamine transporter

what does VMAT do?

transports free cytoplasmic NAdr, 5HT, DA in presynaptic nerve terminal into storage vesicles

how does reserpine lead to depression?

* reserpine irreversibly blocks VMAT * cytoplasmic monoamines cannot re-enter vesicles * instead degraded by MAO and COMT * leads to long-lasting depletion * takes days-weeks to replenish new VMAT

how is rapid tryptophan depletion achieved?

drinking mixture of LNAAs devoid of tryptophan

iproniazid was developed for TB - what other property does it have?

antidepressant as it is a monoamine oxidase inhibitor

what type of MAOIs are used in antidepressive therapies?

MAOA

what type of MAOIs are used in parkinson's disease?

MAOB - increases dopamine

how do MAOIs work?

* inhibit monoamine oxidase * neuronal and synaptic levels of monoamines increases

list an irreversible MAO-A inhibitor?

phenelzine

name a reversible MAOAI?

moclobomide

what is important about diet when taking MAOA inhibitors?

can't metabolise other monoamines eg. dietary tyramine (red wine, cheese, marmite) - could result in hypertensive diet

what is the levels of monoamine oxidase A activity in depressed pts?

high - leads to chronically low synaptic 5HT and NA

how does imipramine work in depression?

* reversibly blocks SERT and NAT * increases synaptic 5HT and NA by reducting degradation

list 3 tricyclic ADs

desipramine amitriptyline clomipramine

desipramine, amitryptyline, clomipramine are all what type of antidepressant?

tricyclic

list 3 SSRIs

fluoxetine paroxetine flucoxamine sertraline citalopram

fluoxetine, paroxetine, flucoxamine, sertraline, citalopram - what type of antidepressant are these?

SSRIs

what are SNRIs?

serotonin and noradrenaline reuptake inhibitors

list 2 SNRIs

venlafaxine duloxetine

venlafaxine and duloxetine are examples of what type of antidepressant?

SNRIs

what does each antidepressant block?

tricyclics and SNRIs - SERT and NAT SSRIs block only SERT

what is the common outcome of all antidepressants?

increase synaptic 5-HT levels

mirtazapine is a new AD that is dual acting by blocking only a single receptor type - what is its mechanism of action?

* adrenergic alpha2 receptor antagonist (blocks) * blocks negative feedback which tends to reduce NAdr release * net effect is increased NAdr release * also blocks negative feedback that reduces 5HT release * net effect is increased 5HT

what is the kindling hypothesis of depression?

* depressive episodes become more easily triggered over time

as the number of depressive episodes increases, future episodes are predicted more by what?

the number of prior episodes, rather than by life stress

the ventral neural system is important for what?

identification of emotional significance of stimuli and production of affective states

what is the dorsal neural system important for?

integration of emotional inputs and the performance of excutive functions

how are the dorsal neural system and ventral system abnormal is MDE?

dorsal neural system - underactive ventral system - overactive

in MDE the dorsal neural system is underactive - what symptoms are associated with this?

* DLPFC and dorsal ACC - apathy, deficits in attention and working memory * **hippocampus - impaired memory consolidation**

in MDEs the ventral system is overactive - what symptoms are associated with this?

* ehanced sensitivity to pain * ventral ACC - depressed mood * **amygdala - preferential processing of negative stimuli compared to positive**

what functional changes happen in the amygdala in MDD?

* overactive when shown sad stimuli * underactive when shown positive stimuli

what is the role of the amygdala?

* modulates visual and attentional processing, particularly facial expression

what structural changes occur in the amygdala during depression?

enlargement

MDD is associated with what bias?

negative cognitive bias

what reverses the negative cognitive bias in depressed pts?

elevated 5HT

what is the most efficient treatment for MDD?

combined antidepressants and CBT

longer durations in which depressive episodes go untreated is associated with what? what can be the result of this?

* reductions in hippocampal volumes * associated with treatment resistance

what stress hormone is consistently high in pts with MDD?

cortisol

consistently high cortisol cannot be supressed by dexamethasone in pts with MDD - what does this suggest?

* their is dysfunction in the HPA axis * drive is coming from hypothalamus

how does chronic stress alter the HPA axis, leading to increased physical illness symptoms and increased risk of inflammatory disorders?

* hypothalamus releases CRH * pituitary releases excessive ACTH (adrenocorticotrophic) * adrenal cortex = excessive glucocorticoid release * increased glucocorticoids dysregulates amygdala function * increased adrenal activity = increased sympathetic tone = increased release of IL 1 and IL6 * IL1 + IL6 + glucocorticoids = increases MAO = decreases 5HT, NA, DA + neurotrophic factors * decreased neurotrophic factors = decreased neurogenesis and hippocampal volume * dysregulation - maintains abnormal levels * increases physical symptoms and inflammatory risk

how does smoking relate to depression management?

ceasing smoking is as effective as starting AD treatment

what is BDNF?

growth factor that is downregulated in depression affecting structural and functional processes within the limbic system, especially hippocampus

what are the NICE guidelines for treatment of mild depression?

* only consider antidepressants if there is history of depresison * offer low-intensity psychosocial intervention- CBT, group physical activity programme

what are the NICE guidelines for management of moderate or severe depression?

* combination of antidepressant medication and CBT

what are the NICE guidelines for antidepressant step-wise appraoch?

* SSRI * change to venlafaxine, mirtazapine, escitalopram or vortioxetine * add augmenting agent eg. 2nd gen antipsychotic or lithium * change antidepressant to tricyclic - amitriptyline or clomipramine * change to MAOI eg. phenelzine

what antidepressants are more effective than others?

agomelatine amitriptyline escitalopram mirtazapine venlafaxine paroxetine

what are the least effective antidepressants?

fluoxetine reboxetine fluvoxamine trazodone

how long should ADs be continued after full recovery from MDE to prevent relapse?

9 months

how do CBT and ADs compare for: * acute efficacy? * long-lasting protective effect after course ends>

acute efficacy - similar long-lasting protection - CBT is better

what are the guidelines for treatment-resistant depression?

* check diagnosis + alcohol and/or drug misuse * antidepressant trials, bupropion * ECT * neurosurgery - bilateral cingulotomy, deep brain stimulation, vagus nerve stimulation

what is the most effective AD treatment? what is a drawback of this?

* electroconvulsive therapy * relapse risk is very high

6 - Depression Flashcards

(84 cards)