Session 3

Question 1

Family/twin/adoption findings?

Answer 1

Unipolar and bipolar depression run in families
More correlation between MZ twins than DZ twins
More correlation with biological parents than adoptive parents

Question 2

Two main forms of inheritance?

Answer 2

Single major locus with variable penetrance

Quantitative trait loco (many genes involved)

Question 3

What is linkage?

Answer 3

Co-occurrence with a known disease & known location is measured

Question 4

What is association?

Answer 4

Co-occurrence of an allele at a particular locus and disease

Question 5

What are association studies?

Answer 5

Examination of many common genetic variants in different individuals to see if variant is associated with a trait.
Two stage process:
1. Systematic polymorphism detection
2. Association studies of disease comparison

Question 6

Association study findings?

Answer 6

Serotonin gene (chromosome 17) and BDNF (chromosome 11) have been implicated
Only genetic load of copy number variants has been significant, but not BDNF or serotonin transport itself

NO CLEAR POSITIVE FINDINGS

Question 7

Role of environment on genetics?

Answer 7

Can change a person’s sensitivity to traumatic events
Can have effect on people’s environment (encounter more accidents and life events)

Childhood maltreatment can cause epibenthic changes

Question 8

Sex differences?

Answer 8

No clear genetic link

Main reasons for sex differences:

• under reporting by men
• environmental factors
• employment status

Question 9

What is the monoamine hypothesis?

Answer 9

Depression is caused by the under activity in the brain of monoamines such as dopamine, serotonin, and noradrenaline

Tested by:

1) biochemistry of neurotransmitters in patients with mood disorders
2) effect of selective drugs on neurotransmitter systems and on mood
3) pharmacological properties of antidepressants

Question 10

Noradrenaline functions in the brain?

Answer 10

Mood
Behaviour
Memory

Question 11

Where is NA made?

Answer 11

Locus coeruleus in the brainstem, transported to several areas of the cortex

Question 12

Evidence of NA in depression

Answer 12

AMPT inhibits tyrosine L-DOPA, so less NA - causes depressive symptoms

Question 13

Antidepressants targeting NA?

Answer 13

NARIs
SNRIs
TCAs

Question 14

Serotonin role in brain

Answer 14

Sleep
Appetite
Impulse control
Mood

Question 15

Where is serotonin produced?

Answer 15

Raphe nuclei in the brainstem

Tryptophan - 5-HTP - serotonin - N-acetyl serotonin - melatonin

Question 16

Evidence for serotonin role in depression

Answer 16

Depletion of serotonin metabolites in depression
Tryptophan depletion causes depression
PET scan: reduced receptor binding in depression
SPET scan: decreased 5HT reuptake sites in the brain

Question 17

Antidepressants targeting serotonin

Answer 17

SSRIs
TCA
SNRIs

Question 18

Dopamine and mood disorders

Answer 18

Role in Parkinson’s
Release can give a feeling of pleasure (cocaine and amphetamines)
ECT has effect on dopamine system
Main neurotransmitter in schizophrenia

Question 19

GABA in depression

Answer 19

Most important inhibitory neurotransmitter in the brain
Low in major depression
A and B receptors
If activated membrane permeability for chloride increases, inhibitory effect on neurone

Question 20

Neurotransmitter changes in mania

Answer 20

NA increased in manic phase
Serotonin findings inconsistent
Antipsychotics block dopamine and have anti-manic properties

Question 21

Role of mood stabilisers?

Answer 21

Lithium
Positive effect on BDNF transcription
Possible positive effect on serotonin production

Question 22

How to investigate a genetic link?

Answer 22

Family studies
Twin studies
Adoption studies
Models of transmission
Sex differences
Linkage/association