Depression Flashcards
(35 cards)
1
Q
What are the two major forms of depression?
A
- Unipolar depression: Low level mood affecting QOL, treated with antidepressants and CBT
- Dysthymia –> low level chronic depression
- Major depressive disorder –> clinical depression and atypical depression
- Bipolar depression: Recurrent cycles of mania and depression, treated with antipsychotics
- Cyclothymia –> periods of mild elation and mild depression, low level bipolar
- Bipolar disorder
2
Q
What is the ICD 10 definition of Bipolar Disorder?
A
- Disorder characterised by 2 or more ep’s in which patient’s mood and activity levels are significantly disturbed
- Disturbance consisting of:
- Elevation of mood/ activity –> hypomania and mania
- Depression of mood/ activity –> Depression
3
Q
What are the two key symptoms of depression
A
- Persistent sadness/ low mood
- Marked loss of interest and pleasure
If one or both of these key symptoms are present look for additional symptoms, need 2/3 more for the diagnosis of clinical depression
4
Q
List:
Key symptoms of depression
Other symptoms looked for
A
- Key symptoms:
- persistent sadness/ low mood
- marked loss pleasure/ interest
- Others:
- ↓ ↑ sleep/ appetite/ weight
- fatigue/ lethargy
- inability to concentrate
- indecisiveness
- feelings of guilt or worthlessness
- suicidal ideation
- decreased movement
- agitation
5
Q
What are the 3 major grades of depression
A
- mild:
- key symptoms, and few if any more symptoms above the 5 required to make diagnosis
- mild impact on functioning
- moderate:
- inbetween mild and severe
- severe:
- most if not all symptoms of depression above that of the 5 required for diagnosis
- major impact on functioning
- can occur with psychotic symptoms
6
Q
What are the diagnostic criteria for depression?
ICD 10
DSM V
A
- ICD 10 –> 2 of the key symptoms plus 4 more
- DSM V –> at least 1 of the 2 key symptoms and at least 5 or more symptoms, occurring everyday for at least 2 weeks for diagnosis of mild depression
- or occuring for more than 2 years for chronic depression
7
Q
What is the circuitry involved in depression?
A
- balance between the postive reward pathway and the negative/stress emotions produced by the amygdala
- change in volume: ↑ amygdala volume ↓ hippocampal volume
- Postive reward p/w –> VTA –> Nucleus accumbens –> prefrontal cortex (+ve emotion)
- Negative emotions –> amygdala
- Amygdala and prefrontal cortex linked via uncinate fasciculus
8
Q
What are some of the electrophysiological changes in depression?
A
- ↓ activity in prefrontal cortex and hippocampus
- ↑ activity in amygdala and hypothalamus
- ↑ hypothalmic pituitary adrenal axis –> increased cortisol and stress response
9
Q
What are 4 theories that could help explain the pathophysiology of depression?
A
- Monoamine transmitter theory –> excess of 5HT/ NA leads to mania, defecit leads to depression
- Neurohormonal theory –> overactivity of the HPA axis, excess CRH from hypothalamus leading to excess Cortisol and stress response
- Autoimmune theory –> immune dysfunction (from stress and infections) altering the inflammatory response, alters metabolism of neurones, altering neuronal circuitry.
- Circadian theory –> changes in circadian rhythm enhancing HPA axis
10
Q
What is the monoamine theory of depression?
A
- main biochemical theory based on altered concentrations of 5HT and NA
- Depression –> defecit
- Mania –> elevation
11
Q
What is the neurohormonal theory of depression?
A
- This theory ties into the monoamine theory
- The hypothalamus is responsible for the release of CRH (Corticotropin releasing hormone) which controls the release of ACTH (adrenocorticotropic hormone) –> controls release of cortisol (stress hormone).
- Altered 5HT/ NA inputs into the hypothalamus can alter the secretion of CRH from hypothalamic parvocellular neurons
- ↑ concentrations of CRH seen in brains of depressed patients, ↑ HPA axis and stress behaviour
- Also increase R expression for CRH in amygdala
12
Q
what is the autoimmune theory of depression?
What is the link between inflammation and depression?
A
- Autoimmune theory –> the idea that changes in inflammatory response (either caused by stress or infections) leads to altered neuronal activity and pathways.
- Inflammation links to depression as there is the idea that inflammatory mediators produced in the brain itself leads to:
- microglial activation
- cell dysfunction and death
13
Q
What is the circadian theory of depression?
A
- Changes in circadian pattern feed into the HPA axis, increasing stress response
14
Q
Where is serotonin mainly produced in the brain?
What are its actions?
A
- Serotonin mainly produced in the Raphe nuclei in the brainstem
- Raphe nuclei run all the way down midline of the brainstem, 5HT is cycled up to the brain, w/in brainstem and down the spinal cord
- Serotonin also produced in the ENS
- Main actions of 5HT:
- Modulate the pain pathway
- appetite, nausea, vomiting, GI function
- mood/ agitation/ anxiety/ OCD
- sexual function and insomnia
15
Q
Where is NA produced?
Where is it circulated?
What are its main actions?
A
- NA produced in nucleus coeruleus and lateral tegmental area (LTA)
- Circulates up to cerebrum and thalamus, around brainstem, down to cerebellum and spinal cord
- Main actions:
- BP and HR
- Energy homeostasis
- Muscle action
- Attention/ agitation/ depression/ emotion
- bladder function
16
Q
What is the interaction between 5HT and NA?
How does this affect release?
A
- NA and 5HT projections from brainstem to cortex run closely alongside each other and interact strongly
- interaction dependent on the expression of adrenergic R subtypes (a1 or a2) presynaptically on dendrites and the presynaptic terminal at synapse of 5HT neuron.
- Accelerator response –> release of NA and binding to alpha 1 at dendrite increases 5HT release
- Dampening response –> release of NA and binding to alpha 2 receptor on presynaptic terminal at synapse inhibits 5HT release
17
Q
What is the Gut brain axis?
How might it be involved in depression?
A
- Describes the interaction between the gut microflora, the gut epithelium, the circulation and the brain. There is bidirectional communication between the gut and the brain via the Enteric NS, autonomic NS, neurohormonal system and circulation.
- When we are born the gut is colonised by commensural bacteria.
- These form the gut microbiota which is required for healthy gut epithelial barrier. Inflammation can damage the microbiota and lead to a leaky gut epithelial barrier.
- This allows inflammatory mediators/ NTs/ fatty acids to cross the epithelial barrier and enter the circulation
- Carried to the brain, where it can alter neuronal activity at regions of cerebral vasculature damage or leaky sites of the BBB (i.e hypothalamus).
- 5HT also produced by the gut, altered gut function alters the amount of 5HT available
18
Q
What are the changes seen at the neuronal level in depression?
A
- Normally dendrites covered in many BOUTONs which are terminal club shaped projections occuring at synapses and often are a site of NT store.
- Each dendrite often covered in multiple boutons on each branch of dendrite, therefore many connections can be made in one area
- In depression there is reduced number of bouton and reduced number of arborizations of dendrites
- ↓ connections between neurons –> leads to receptor overexpression
- Defecit in synapse number and R overexpression
- this can be reversed by GF’s (BDGF) and by antidepressants
19
Q
what are the treatment options for depression?
A
- CBT
- Pharmacological:
- SSRI’s
- TCA’s
- MAOI’s (type A depression, B parkinson’s)
- atypical
- Brain stimulation:
- ECT –> electroconvulsive therapy (gold standard)
- TMS —> transcranial magnetic stimulation
- tDCS —> transcranial direct current stimulation
20
Q
What is TMS?
What are its advantages?
A
- Transcranial magnetic stimulation:
- alternating magnetic fields are used to stimulate neurons in the brain, targeted at limbic system and prefrontal cortex
- can alter LTP and LTD
- can affect NT’s and affect neuronal plasticity
- Advantages:
- less stigma than ECT
- Good for severely depressed patients not responding to pharma
21
Q
What is tDCS?
A
- tDCS —> transcranial direct current stimulation
- slow, low level electrical current applied for 20-30 mins, patient awake and alert
- low and slow approach to alter cortical activity
22
Q
What is ECT?
What are its advantages and disadvantages?
A
- Electroconvulsive therapy –> gold standard for severe depression, 50% patients respond
- short sharp jolt to the brain
- huge stigma but can be very effective
- side effects: muscle ache and memory loss
23
Q
Name two SSRI’s
What is the MOA?
What are potential problems?
A
-
SSRI’S —> SeaRch to lean and sit in a low pram:
- Sertraline
- Citalopram
- MOA: inhibits reuptake of Serotonin by inhibiting the serotonin transporter (SERT), increasing 5HT at the synapse
- Problems: Slow onset of action due to negative feedback via 5HT1A receptors on presynaptic terminals that need to desensitise to the increase in 5HT.
- Can be disheartening for patients
24
Q
Name two SSRI’s
What are the side effects?
A
- Citalopram and sertraline
- Side effects:
- increased bleeding
- nausea
- insomnia
- sexual dysfunction
25
What is the serotonin reaction?
* serotonin reaction is a reaction to medications that elevate 5HT (e.g. SSRI'S, MAOI'S) and symptoms can be severe:
* hyperthermia and aggression
* tremor and rigidity
* cardiovascular collapse -\> tachycardia and HTN
* diarrhoea
26
Name three atypical antidepressants that also inhibit reuptake
What are their MOA's?
* NRI --\> Noradrenaline reuptake inhibitor
* reboxitine
* SNRI --\> Serotonin and NA reuptake inhibitor
* venlafaxine
* DNRI --\> dopamine and NA reuptake inhibitor
* Buproprion
27
Name an atypical antidepressant that helps to reset the neurone?
* **Buspirone = 5HT1A R partial agonist**
* By acting as a partial agonist to the 5HT1A receptor this reduces the activity of 5HT neurons, allowing the neuron to slow down and reset
* Increases the amount of NT in the synaptic terminal and can allow post synaptic receptor density to reset
* Stronger response next time the neuron fires
28
What pharmacological treatment alters sleep pattern?
* Agomelatine = melatonin agonist
* Enhances slow wave sleep
* very effective in some forms of depression but NICE have not approved
29
Which atypical antidepressant treatment alters 5HT /NA interaction?
* **Mirtazapine = alpha 2 adrenoreceptor antagonist** (two a's therefore alpha 2 adrenorecptor block)
* Alpha 1 normally accelerates 5HT release, Alpha 2 receptors dampen response and slow 5HT release.
* Therefore alpha 1 agonism and alpha 2 antagonism will enhance 5HT release
30
What are the 5 main actions of TCA's?
* 5HT and NA reuptake inhibitors --\> mainly NA
* A1 adrenoreceptor antagonism
* H1 receptor antagonism
* M1 receptor antagonism
31
Name two TCA's
What are the side effects?
What should you be aware of in these patients?
* The Norti CAT Trypt Ami
* Nortriptyline
* Amitryptyline
* Side effects linked to a1 adreno R, H1 histamine and M1 Ach R antagonism:
* Ach R: dry mouth, blurred vision, constipation, urinary retention
* A1 AdrenoR: postural hypotension, cardiac dysrhythmia
* Histamine: Sedation, confusion, drowsiness
* Mania
* TCA's rely on CYP enzymes for their metabolism and elimination, therefore there are multiple interactions from aspirin to alcohol.
32
What antidepressant drug inhibits breakdown of NT?
What is its mechanism of action?
Why should we be careful with this drug?
* Moclobemide --\> Reversible MAOI (type a in depression)
* Increases 5HT and NA by inhibiting its breakdown
* WARNING: never give with another SSRI/ TCA as multiple drug reactions
33
What are the side effects of moclobemide?
* Postural hypotension
* restlessness
* insomnia
* convulsions in OD
* Atropine like effects --\> dry mouth, blurred vision, constipation, urinary retention
* increased appetite and weight gain
34
What is the cheese reaction?
* Cheese reaction is caused by excessive tyramine
* Tyramine is contained in cheese and is normally broken down by MAO in gut and liver before reaching the circulation
* MOA-I's prevent breakdown of tyramine
* Tyramine = sympathomimetic --\> leads to:
* hypertension and headache
* severe cases intracranial haemorrhage
35
What is lithium used for?
* Lithuim is a mood stabiliser used in the treatment of Bipolar disorder or as an adjunct to antidepressants for resistant recurrent unipolar depression
