Session 3 Flashcards
Family/twin/adoption findings?
Unipolar and bipolar depression run in families
More correlation between MZ twins than DZ twins
More correlation with biological parents than adoptive parents
Two main forms of inheritance?
Single major locus with variable penetrance
Quantitative trait loco (many genes involved)
What is linkage?
Co-occurrence with a known disease & known location is measured
What is association?
Co-occurrence of an allele at a particular locus and disease
What are association studies?
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
Association study findings?
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
Role of environment on genetics?
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
Sex differences?
No clear genetic link
Main reasons for sex differences:
- under reporting by men
- environmental factors
- employment status
What is the monoamine hypothesis?
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
Noradrenaline functions in the brain?
Mood
Behaviour
Memory
Where is NA made?
Locus coeruleus in the brainstem, transported to several areas of the cortex
Evidence of NA in depression
AMPT inhibits tyrosine L-DOPA, so less NA - causes depressive symptoms
Antidepressants targeting NA?
NARIs
SNRIs
TCAs
Serotonin role in brain
Sleep
Appetite
Impulse control
Mood
Where is serotonin produced?
Raphe nuclei in the brainstem
Tryptophan - 5-HTP - serotonin - N-acetyl serotonin - melatonin
Evidence for serotonin role in depression
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
Antidepressants targeting serotonin
SSRIs
TCA
SNRIs
Dopamine and mood disorders
Role in Parkinson’s
Release can give a feeling of pleasure (cocaine and amphetamines)
ECT has effect on dopamine system
Main neurotransmitter in schizophrenia
GABA in depression
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
Neurotransmitter changes in mania
NA increased in manic phase
Serotonin findings inconsistent
Antipsychotics block dopamine and have anti-manic properties
Role of mood stabilisers?
Lithium
Positive effect on BDNF transcription
Possible positive effect on serotonin production
How to investigate a genetic link?
Family studies Twin studies Adoption studies Models of transmission Sex differences Linkage/association
