Depression

Question 0

Depression neurocircuitry

Answer 0

May share anxiety neurocircuitry
Orbital and pfc
Amygdala
Ventral striatum
Hippocampus
Hypothalamus
Cingulate gyrus

Question 1

What is depression

Answer 1

Sad mood, loss of interest, abnormalities of sleep, appetite, energy
Frequently comorbid with anxiety disorders
Associated neuroendocrine disruption,
excessive CRF release

Question 2

Role of serotonin

Answer 2

Made from l typtophan
Metabolised by monoamine oxidase
Made in raphe nuclei
1abdefR activated by triptans
2abcR activated by hallucinogenic drugs
3-7 ionotroohic, blocked by ODANSERON LIKE ANTIMEMTICS

Question 3

Role of noradrenaline

Answer 3

Tyrosine to dopamine to na
Made in locus coeruleus
Alpha and beta are metabotrophic

Question 4

Role of dopamine

Answer 4

Made in ventral midbrain, 
Sub nigra= movement
Ventral tegmentum area= reward, novelty, motivation
Innervates striatum, limbic and pfc.
Metabotrophic
1= excit galphas
2= inhib galphai

Question 5

Tricyclic drugs

Answer 5

AMITYPTYLINE, IMIPRAMINE, CLOMIPRAMINE
inhibit serotonin and na reuptake
Block mAch, dry mouth, no tears
Histamine= drowsy
Alplha 1 adrenic= vasodilation, hypotension

Question 6

Drug drug interactions with tricyclic drugs

Answer 6

+ adrenergic vasoconstrictors = arrhythmia
+ barbituates =’severe respiratory depresion
+ acetominophen = reduces tca metabolism leads to toxicity.

Question 7

SSRIs

Answer 7

CITALOPRAM
FLUOXETINE
FLUVOXAMINE
PAROTEXETINE
SERTRALINE
selectively inhibit 5ht transporter, sexual dysfunction, weightgain
Decrease metabolism of codeine, benzos

Question 8

NRIs

Answer 8

REBOXETINE
ATOMOXETINE
inhibit na uptake

Question 9

Atypical antagonist

Answer 9

BUPROPRION
poorly understood mechanism
Inhibits da reuptake, minimally occupies dat
MITRAZAPINE
antagonist at alpha 2 5ht2a and 3rs 
Mechanism unknown

Question 10

SNRIs

Answer 10

VENLAFAXINE, DULOEXTINE
inhibit 5ht and na uptake
Used for ptsd

Question 11

Monoamine oxidase inhibitor

Answer 11

IDRONIAZID
inhibits breakdown of monoamines,
Maob breaks down 5ht and histamine
TRANYLCYPROMINE, PHENELEZINE, 
Tyramine containing foods cause adrenic storms with maois, keeps na in synapse for longer

Question 12

Problems with monoamine antidepressants

Answer 12

Probably dont work by known mechanism
Only half patients respond to them
Clinical benefit seen after 7-8 weeks

Question 13

Antidepressants are bad with what?

Answer 13

St johns wort (hyperforin)
Induces drug metabolising enzymes
Amount of active ingredient varies between different preparations

Question 14

Animal models of depression

Answer 14

Models of stress not depression,
Swim, tail
Observe social isolation and decrease grooming
Reversed with antidepressants?

In vivo models are difficult

Question 15

Monoamine hypothesis

Answer 15

Reduced levels of monoamine causes depression
Antidepressants dont work by their “known” mechanism
Half patients respond to treatment
Effects of monoamine transport is immediate, several weeks to see benefit.
Low tryptophan diet does not produce depression in healthy people

Question 16

Chemical hypothesis

Answer 16

Depression caused by impaired function of particular receptors/channels
Genetic studies
Pathways altered by maois and ssris

Question 17

Network hypothesis

Answer 17

Explains why antidepressants may take weeks to work when effect on nts is immediate

Depression due to long term malfunctions in neural network
Long term alterations in mants, leads to impaired network
Ma’s play a role in neuronal growth and development

Question 18

For network hypothesis

Answer 18

Alterations in ma function early postnatal in animal cause permanent organisational and behavioural disturbances, not seen in adults

Increase new neurone production in hippocampus

Sprouting of axons and dendrites

Question 19

Against network hypothesis

Answer 19

Very low tryptophan levels causes depressive symptoms

Question 20

ECT

Answer 20

Muscle relaxant administered 
25-45s convulsion
Safe
May have ltm defects
Most effective antidepressant, stimulates neurogenesis

Question 21

Deep brain stimulation

Answer 21

Of subgenual cingulate cortex
Used when all else fails
Dont know how it works, atp release?

Question 22

Future treatments?

Answer 22

Multi-modal serotonergics
Triple uptake inhibitors
Neurokinin r antagonists
Nmda antagonists, may induce bdnf
Crf receptor antagonists

Question 23

What is agomelatine?

Answer 23

Melatonin r agonist
Increase dopamine and na in pfc
Sleep phase shifts in depression
No weight gain
But melatonin not a great antidepressant

Question 24

Bipolar

Answer 24

Mood stabilisers:
Lithium carbonate ( inhibits release of da and na)
Carbamazepine ( anticonvulsant blocks na+ channels interacts with adenosine r)
Valproate na (anticonvulsant, increases gaba, blocks na channels)
Antidepressants
Antipyschotics and benzodiazepines