Monoamine Hypothesis

Question 1

What is depression?

Answer 1

Affective disorder - extreme or inappropriate mood

In DSM - included bipolar disorders, depression vs in DSM-5 - disorders are placed in a different section

Question 2

What is depression called?

Answer 2

Major depressive disorder

Question 3

What is major depressive disorder?

Answer 3

Depressed mood, and or anhedonia (loss of pleasure) plus 5 or more others from the following list for nearly everyday for 2 weeks:
body weight changes
sleep changes
motor retardation
fatigue or loss of energy
worthlessness or guilt
diminished ability to think or concentrate
recurrent thoughts of death or suicide - with or without a plan

Question 4

How common is depression?

Answer 4

5% of the population are depressed at any point in time
30% of the population have had at least 1 episode of depression
30,000 suicides in the USA per year
3 times more likely in women than in men

Question 5

Is it heritable?

Answer 5

Moderate heritability 37%
2-3 times more likely to have depression if our relatives are diagnosed with MDD
Several genes have been linked to depression - different genes may involved GWAS
Concordance rate goes up for MZ twins compared to DZ twins but still a lot of room for environmental factors

Question 6

Why is depression different to others?

Answer 6

The HPA axis is involved

Question 7

What is the monoamine hypothesis?

Answer 7

Depressive symptoms are caused by insufficient activity of the monoaminergic neurons - monoamine agonists should be able to reverse the symptoms

Question 8

Types of monoamines

Answer 8

Dopamine
Norepinephrine
Epinephrine
Serotonin

Question 9

What is the process of reuptake and enzymatic degradation?

Answer 9

1. Vesicles and peptides neurotransmitter are synthesized
2. Transport
3. Storage and synthesis of smaller neurotransmitters
4. Action potential causes calcium ions to enter and triggers NT release
5. Neurotransmitter molecules across synapse
6. NT molecules attach to recepotrs and cause postsynaptic activity
7. Reuptake of molecules
8. NT is broken up by the monoamine oxidase

Question 10

What are the ways that NT are reuptaken?

Answer 10

Reuptake by transporter proteins or broken up by enzyme monoamine oxidase

Question 11

What does MAO’s do?

Answer 11

It is an enzyme which inactivates monoamines - breaks down monoamine so less to be released

Question 12

What is the early evidence pointing towards a chemical imbalance?

Answer 12

Lower levels of the serotonin in the CSF of depressed individuals
lower levels of dopamine metabolites or norepinephrine metabolites in the CFS of depressed individuals
these findings have been small and inconsistent - changes in metabolites may not be the best way of measuring subtle changes in NT function

Question 13

What is reserpine?

Answer 13

Used to treat blood pressure in the mid-20th century - caused depression in patients as a side effect
Blocks the packaging of monoamines into the vesicles so when the neurons are activated no NT is released -dysfunction in monoamines could lead to depression

Question 14

What do effective antidepressants affect?

Answer 14

Serotonin - increase serotonin

mood elevating substances e.g. amphetamines, and ecstasy elevate monamine levels

Question 15

What was the first treatment for depression?

Answer 15

MAO inhibitors - e.g. iproniazid - this inhibits the breakdown of monoamines in the presynaptic terminal, increasing the level taken up to the vesicles

Question 16

What are the side effects of iproniazid?

Answer 16

Cheese effect - cheese like products contain tyramine which is normally deactivated by MAO in the liver. In the presence of MAO inhibitor, tyramine isn’t broken down, results in the stimulation of the sympathetic nervous system and an increase in heart rate and blood pressure - need to be mindful of what they eat, goes hand in had with diet

Question 17

What are other antidepressants?

Answer 17

Tricyclic antidepressants - inhibit the reuptake of 5-HT and NE - indirectly enhancing, increasing monoamine by igniting the reuptake. Effects heart functioning

Selective serotonin reuptake inhibitors were synthesised, with prozac being the first one - block the transporter, so there is more serotonin, only drug children can have
Side effects but not as bad

SNRI’s - serotonin - norepinephrine reuptake inhibitors - less side effects than tricyclic

Question 18

What are the problems with the monoamine hypothesis?

Answer 18

It is too simple - an acute decrease in serotonergic activity in healthy people has no effect on mood, only those with a history of depression

Time course

Question 19

Why is time course a problem with the hypothesis?

Answer 19

Although the SSRIs and SNRIs increase the levels of 5-HT or NE very quickly, the drugs do not relieve the symptoms of depression for several weeks (3-7). Inconsistent with the hypothesis, chemicals are increased very quickly after taking it, but the symptoms aren’t reduced, something other than an increase in activity is responsible for the normalisation of mood

Question 20

Why is the hypothesis too simple?

Answer 20

Reducing serotonin - deleting tryptophan - in healthy people didn’t cause any depression, unless they were susceptible, then they showed the symptoms (differences in the brains of vulnerable people)
Cant just look at chemicals in isolation