Lecture 8 Flashcards

1
Q

How is depression diagnosed?

A

Symptoms of low mood need to persist of 2 weeks and abrupt normal life.

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2
Q

How can depression arise?

A

40% inherited, can arise due to concussions and can’t be narrowed down to a single brain region

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3
Q

What is unipolar depression?

A

mood swings in one
low mood
anadenia= inability to take pleasure from activities
extreme loss/gain of weight
reactive type (75%)= specific trigger e.g. stressful situations
endogenous= no clear cause

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4
Q

What is bipolar depression?

A

Low mood alternating with mania
extreme positive feelings characterised with euphoria and aggression or irritability
caused by stressful situations
40% have family with depression but no gene related and no singular brain region

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5
Q

What are the typical symptoms of depression?

A
libido loss= loss of sex drive 
anhedonia
low mood, aggression, feelings of guilt 
apathy= extreme loss or gain of weight 
sleep disturbances= insomnia or excessive sleeping
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6
Q

What are the brain regions effected by depression?

A
  1. Mesolimbic dopamine circuit= increase in BDNF
  2. Decrease in BDNF in the hypothalamus due to cortisol
  3. Amygdala= associated with fear response
  4. Ghrelin95 and leptin 96= metabolic hormones released due to hypothalamus activity
  5. Increased stimulation in nucleus accumbans alleviates depression. Release of dopamine mediates suseptability of social stress
  6. Limbic system and ventral tegmental area= involved in mood and reward
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7
Q

What is postnatal depression?

A

Depressed mothers can have depressed babies
occurs 2-8 weeks after birth
brainwaves in the baby can be affected and can grow up to have depression
mother’s behaviour can cause epigenetic changes in the baby

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8
Q

Describe depression and society

A

Many people don’t get help
counselling and antidepressants are recommended
anti-depressants are important due to change in brain chemistry that can only be reversed by drugs even though cause is gone

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9
Q

How are animal models used to test antidepressants?

A
  1. Swim test= swim until they give up and become depressed
  2. Suspend from tail then give up
  3. place in confined space
  4. Stressful situations for several weeks that is unpredictable= they acquire similar brain activity to stressed humans
    Give them ADs and they persist to escape stressful situations- more immediate effects for acute stress not chronic
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10
Q

What are the physical causes of depression?

A

No change in gross anatomy but little evidence in pathology= increase in cortisol

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11
Q

What is the monoamine hypothesis?

A

Drugs that cause monoamine depletion e.g. reserpine cause depression

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12
Q

How do MOA inhibitors relieve symptoms of depression?

A

They inhibit the depletion of monoamines- take a while to work as they need to alter transcription

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13
Q

What else is implicated in chemical depression?

A

BDNF binds to trk B which is controlled by serotonin
glutaminergic neurodegeneration is also implicated
increase in CREB in hippocampus

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14
Q

How are receptors effected in depression?

A

5HT 1b R= beneficial change in transcription- increase p11 in the cortex- in depression they have reduced signalling and causes apoptosis and loss of synapses
glutamate causes excess activation of NMDARs which results in neurodegeneration

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15
Q

Reserpine

A

Causes depletion of monoamines which causes depression and Parkinson’s

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16
Q

Iproniazid

A

first specific MAO inhibitor

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17
Q

How do tricyclic anti-depressants work? e.g. imaprimine

A

They are involved in the reuptake of NA and 5HT- inhibit their transporters

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18
Q

What do monoamines modulate?

A

dopamine from ventral tegmental area
5HT from dorsal raphe
NA from local coeruleus
areas known to control awareness, emotion alertness

19
Q

Moclobemide

A

MOA inhibitor- more selective for A type in CNS

side effects= increase in sympathetic drive and NA

20
Q

phenylzine

A

MAO inhibitor like moclobemide. Irreversible, non-competitive inhibitor

21
Q

fluoxetine

A

selective 5HT uptake inhibitors- can be not that effective due to NA component

22
Q

MA R antagonists

A

Alpha 2 adreno and 5HT1/2 have been implicated

23
Q

What is the principle action of ADs?

A

They inhibit breakdown of monoamines- 5HT>NA>DA

Have side effects= NA depletion from vesicles

24
Q

What is the cheese effect?

A

Cheese, wine and other foods contain tyramine- when you have MAOI= more monoamines leaking out of the neurons which results in sympathetic discharge therefore increase in BP

25
Q

What are type A ADs?

A

reversible e.g. moclobemide

26
Q

TCAs

A

inhibit reuptake of 5HT and NA- preferred over MAOIs
side effects= anticholinergic, adrenergic and histaminergic (sedation)
dangerous overdose- can cause cardiotoxicity due to block of HERG receptors

27
Q

SSRI

A

inhibit uptake of 5HT

28
Q

NARI (reboxetine)

A

Inhibit NA reuptake

29
Q

What is the NA pathway in the CNS?

A

Main source of signalling= amygdala
involved in BP regulation, mood, sensory regulation, pain, arousal/attention, sleep increase, withdrawal and anorexia
Inhibition of reuptake in frontal cortex using NARIs improves mood

30
Q

How do NARIs like reboxetine work to inhibit NA reuptake and how does this effect tyramine?

A
Inhibits MAO (similar to COMT) which is found EC and IC to break down NA. 
NA has a similar structure to tyramine therefore it won't be processed by MAO when inhibited- increase in tyramine which results in it replacing NA in vesicles
31
Q

How can neurons that secrete NA be identified?

A

They express dopamine beta hydroxylase

32
Q

What does 5HT do in the raphe nucleus?

A

They are stimulated by alpha 1Rs and downregulates alpha 2 Rs which is associated with AD therapy

33
Q

What is the role of 5HT?

A
sleep/wakefulness 
hallucinations 
body temperature 
mood/emotion 
sensory pathway/ nociception 
vomiting 
limbic system to feel pleasure
34
Q

What do 5HT drugs treat and what unwanted side effects need to be avoided?

A

treats anxiety, depression, antipsychotic, chemotherapy

high levels in the gut- want to avoid targeting it

35
Q

describe 5HT production

A

tryptophan- 5 hydroxytryptophan- 5HT- 5HIAA

36
Q

Why is there cross signally between 5HT and NA?

A

Because they control each other’s neurotransmission

37
Q

How can serotonergic neurons be identified?

A

They have tryptophan hydroxylase

38
Q

maprotiline

A

NA selective AD

39
Q

reboxetine

A

NA selective AD

40
Q

desipramine

A

NA selective AD

41
Q

Name 3 non-selective ADs

A

amitriptyline, imipramine, clomipramine

42
Q

Fluoxetine, citalopram

A

5HT selective AD

43
Q

What is the neurotrophin hypothesis?

A

Activation of 5HT receptors causes phosphorylation of CREB which activates BDNF which works retrogradely to stabilise synapses- in depression there is a loss of this and synapses are lost (hippocampus)