Week 17 - The biology of depression Flashcards
What regions of the brain are most associated with depression?
- Prefrontal cortex
- Hippocampus
- Amygdala
Other than the prefrontal cortex, amygdala and hippocampus, what other regions of the brain are relevant to mood?
- Hypothalamus
- Nucleus accumbens
What is the hippocampus important for?
The organisation and retrieval of memories, and the formation and storage of certain kinds of conscious memory such as recollection of facts, associations and events
What type of receptors are expressed in the hippocampus?
Glucocorticoid
As well as the hypothalamus, what two other regions of the brain are involved in regulating the stress response?
- Hippocampus
- Prefrontal cortex
What is the prefrontal cortex important for?
- Reasoning
- Concentrating on the task in hand
- Planning
- Decision making
- Moderating behaviour / regulating mood states
What is the amygdala concerned with?
- Emotion
- Motivation
What substance does the amygdala secrete in order to stimulate the hypothalamus?
CRF - corticotropin-releasing factor
What is the nucleus accumbens known as?
The ‘motivation and reward centre’ of the brain
Feelings of reward will activate which type of pathway in the nucleus accumbens?
Dopaminergic pathways
Dopaminergic pathways in the nucleus accumbens are activated by what type of feelings?
Feelings of reward
What type of behaviour does the release of dopamine in the nucleus accumbens drive?
Reward-seeking behaviour
In people with depression, is the nucleus accumbens more or less active in response to reward?
Less active
What structural change in the hippocampus is noted in people experiencing major depression?
Reduced grey matter volume
What structural change in the prefrontal cortex is noted in people experiencing major depression?
Decreased grey matter volume
What structural change in the amygdala is noted in people experiencing major depression?
Reduced grey matter volume
What functional change is noted in the hippocampus in people experiencing major depression?
Decreased activity
What functional change is noted in the prefrontal cortex in people experiencing major depression?
Decreased activity
What functional change is noted in the amygdala in people experiencing major depression?
Increased activity in response to sad thoughts
What functional change is noted in the nucleus accumbens in people experiencing major depression?
Decreased activity in response to reward
Name two dopaminergic pathways which mediate the effect of reward
- Mesolimbic
- Mesocortical
Which brain regions associated with the HPA axis are also altered in depression?
- Hippocampus
- Prefrontal cortex
- Amygdala
What do high levels of cortisol suggest?
Hyperactivity in the HPA axis of those who are experiencing depression
Do high levels of cortisol cause depression?
No, but the are correlated
High concentrations of cortisol for a prolonged period of time can weaken neurons in which two brain regions?
- Hippocampus
- Prefrontal cortex
Which three regions of the brain are associated with the default mode network (DMN)?
- Medial prefrontal cortex
- Medial parietal cortex
- Medial temporal lobes
What is the function of the default mode network (DMN)?
It is associated with mind-wandering or stimulus-independent thought
When is the DMN (default mode network) active?
During rest, rather than when cognitive tasks are being performed
In those who are experiencing major depression, what effect has been found on the default mode network during periods of rumination?
Regions of the DMN show greater activity than when healthy people ruminate
In which decade were antidepressant medications first discovered?
The 1950s
What is meant by the term monoamine hypothesis of mood disorders?
The hypothesis that depression results from low levels of monoamines (eg serotonin) being available for neurotransmission
What effect does resperine have on the monoamine transmitters serotonin, noradrenalin and dopamine?
It depletes them
What effect does isoniazid have on the enzyme monoamine oxidase?
It inhibits it
When an action potential arrives at the presynaptic side of the synapse, what neurotransmitter is released from the axon terminal into the synaptic cleft?
Serotonin or noradrenaline
What is the name of the enzyme which breaks down serotonin and noradrenaline when they have been taken back into the presynaptic axon terminal?
Monoamine oxidases
What are the three classes of antidepressant medications (ADMs)?
- MAOI (monoamine oxidase) inhibitors
- Tricyclics
- SSRIs
What effect does the inhibition of monoamine reuptake have on monamine transmission?
Neurotranmission will be enhanced as there will be more monoamine in the synaptic cleft
How does the action of MAOIs differ from SSRIs and tricyclics?
MAOIs prevent monoamine oxidase from breaking down monoamine neurotransmitters. Tricyclics and SSRIs prevent monoamine from being taken back into the presynaptic neuron so more monoamine will remain within the synapse
How do MAOI antidepressants work?
They inhibit the activity of monoamine oxidase by preventing the breakdown of monoamine neurotransmitters
Why do MAOI antidepressants work?
The prevention of monoamine neurotransmitter from being broken down means that more neurotransmitter is available to be released at the synapse, where it triggers an action potential
Why are MAOI antidepressants rarely used now?
Because there are a lot of associated side effects and they interact with a lot of other drugs
How do tricyclic antidepressants work?
They act as reuptake inhibitors and block serotonin and noradrenaline reuptake
Why do tricyclic antidepressants work?
As a result of reuptake of serotonin and noradrenaline uptake being blocked, the amount of monoamine in the synapse increases, which can compensate for people with low levels of monoamines
How do SSRI antidepressants work?
They increase the amount of neurotransmitter in the synapse by preventing reuptake
Why do SSRI antidepressants work?
Because uptake is inhibited there is more serotonin available in the synapse
Can monoamine metabolites be detected in CSF?
Yes
Are levels of monoamine metabolites higher or lower in the CSF of people experiencing serious depression and suicidal behaviour?
Lower
What do low levels of serotonin metabolites in the CSF suggest about serotonin levels in the brain?
That levels of serotonin in the brain are low
Which amino acid commonly found in the diet is used for the manufacture of serotonin?
Tryptophan
In what kind of foods is tryptophan found?
Protein-rich foods such as meat, eggs, cheese and soybeans
What function does brain-derived neurotrophic factor have an important role in regulating?
Neurogenesis (the creation of new neurons)
What is the neurotrophic hypothesis?
The hypothesis that reduced brain BDNF levels predispose to depression and that increase in BDNF levels produces an antidepressant action
What has been found from clinical studies investigating BDNF and depression?
That levels of BDNF are decreased in the blood of people experiencing depression but not taking ADMs
Which pathway is hyperactivated by chronic stress to increase cortisol levels in people experiencing depression?
High levels of cortisol are caused by hyperactivation of the HPA axis
A single, intravenous infusion of a low dose of ketamine has been shown to produce what effect?
Antidepressant effects in people experiencing major depressive disorder
Which is the major excitatory neurotransmitter in the brain?
Glutamate
What are ionotropic receptors associated with?
Ion channels in the cell membrane
How many types of ionic glutamate receptors are there?
Three
What are metabotropic receptors?
They are ‘messenger’ molecules which activate particular biological reactions within the cell
Glutamate signalling has a critical role in modulating levels of what?
BDNF (brain-derived neurotrophic factor)
Research in animal models suggests that ketamine exerts its antidepressant effect how?
By increasing BDNF levels
What are cytokines?
Inflammatory proteins in the blood
How do inflammatory proteins such as cytokines enter the brain?
By crossing the blood-brain barrier
What effect can cytokines have once they have passed into the brain?
They can reduce the availability of monoamine neurotransmitters and increase levels of glutamate
