Depression Flashcards Preview

Physioloogy and pharmacology > Depression > Flashcards

Flashcards in Depression Deck (21)
Loading flashcards...
1

What are the two types of depression

Unipolar - low mood -
reactive depression - something triggers it - stressful event
Bipolar - alternation between low and over exuberant moods

2

What regions of the brain are implicated in depression

Cingulate nucleus
Nucleus accumbens - limbic system control of emotion
Hippocampus
Amygdala - involved in the processing of fearful emotions
Peripheral hormonal aspect - increased levels of cortisol (stress hormone)
BDNF - brain derived neurotrophic factor

3

What are symptoms of depression

Low mood, apathy, loss or gain of weight, low self esteem, loss of appetite/libido

4

What is postnatal depression

Occurs in women shortly after birth - children of depressed mothers are more likely to become depressed themselves in later life

5

What is the monoamine theory of depression

proposed in 1965 - suggests depression results from functionally deficient monoaminergic transmission is the CNS
Based on the ability of MAO inhibitors to increase this transmission and drugs such as reserpine to deplete stores of monoamine neurotransmitters and therefore cause depression

6

What is the action of MAO inhibitors

MAO-A found in the CNS
Rapid and sustained increase in 5-HT (and noradrenaline/adrenaline) act by inhibiting uptake of noradrenaline/5-HT by monoaminergic nerve terminals

7

What are some side effects of MAOIs

Exaggerated effects in the peripheral nervous system
Tyramine acts as a catecholamine/monoamine releasing agent - also displaces stored monoamines from presynaptic vesicles - MAO-A breaks down dietary tyramine - if in conjunction with MAOIs - foods high in tyramine are ingested - a hypertensive crisis occurs (vasoconstriction)

8

What is the action of tricyclic antidepressants

Inhibit reuptake of 5-HT and noradrenaline
Tend to affect mAchRs - side effects related to mAchR antagonism
-dry mouth
-Blurred vision
-Constipation

9

What is the action of SSRIs (Specific serotonin reuptake inhibitors)

Inhibit 5-HT reuptake - less side effects and toxicity than TCAs, some patients - SSRI's aren't effective - need to control noradrenaline levels as well

10

What is the action of SNRIs

Specifically inhibit noradrenaline reuptake

11

What is the process of noradrenaline synthesis

Tyrosine - DOPA - dopamine - noradrenaline - adrenaline

12

What is the action of noradrenaline

Binds to alpha and beta adrenoceptors - Alpha2 adrenoceptors in the CNS - this is a negative feedback system so prevents further release of noradrenaline - Noradrenaline action terminated by COMT (catechol-o-methyl transferase)

13

Where are the majority of 5-HT neurons cell bodies found

In the raphe nucleus

14

What are serotonin functions

Hallucinations, mood, feeding behaviour, body temp, vomiting

15

What role does serotonin have on the limbic system

Regulates limbic processing - Decreased serotonin leads to anhedonia - inability to gain pleasure from pleasurable activities

16

How is serotonin synthesised

Tryptophan precursor -present in chocolate
Rate limiting enzyme is tryptophan hydroxylase - produces 5-Hydroxytryptophan - subject to transcriptional regulation
serotonin synthesis in the cytoplasm
Termination of action through reuptake
Breakdown by MAO

17

Why have SSRIs got a slow mechanism of action

Due to need to desensitise somatodendritic 5HT1A receptors
5HT1A is an inhibitory Gi coupled receptor
Acute increase leads to increased activation and a decrease in firing and 5-HT release - negative feedback

18

What happens to 5HT1A when there is a chronic increase in serotonin

Internalisation and degradation of the receptor. Loss of negative feedback inhibition so more action potential firing can occur

19

How do neurotrophins affect depression

Serotonergic neurons regulate production of BDNF - BDNF stabilizes synaptic connections between an active neuron and a dendritic spine
Decreased 5-HT means decreased BDNF - means reduced synaptic stability
These changes are regionally specific - dependent on area - changes in behaviour not necessarily related to depression

20

How is BDNF synthesised

Expression controlled by levels of the CREB transcription factor - which is activated by cAMP, PKA etc - phosphorylation of CREB increases its translocation to the nucleus and its regulation of BDNF transcription

21

What is electroconvulsive therapy

Very effective antidepressant - Downregulates beta receptors and upregulates 5-HT2 receptor sites