The Psychobiology of Depression and Mood (Michelle) Flashcards
How d we put clinical depression into perspective?
- DSM-V criteria are more extreme than the typical fluctuations in mood that we all experience
- Prolonged
- Debilitating
- Prohibit normal functioning
- Not due to bereavement
What is the Stress-Diathesis model?
- Model of depression
- Diathesis means a genetic vulnerability to depression
- Coupled with a stressor increases the likelihood of being diagnosed with depression
What are monoamines?
- Family of neurotransmitters
- Norepinephrine (NE: noradrenaline (NA))
- Serotonin (5-HT)
- Dopamine (DA)
What is the excitatory noradrenergic synapse pathway
- Production of NA
- NA release from vesicles at the synaptic cleft
- Activation of postsynaptic receptors
- Activation of autoreceptors
- Re-uptake unto presynaptic neuron
- Breakdown or storage
What does norepinephrine stimulate in the brain?
- Mood
- Attention
- Motor control
- Emotion
- Energy
What does serotonin stimulate in the brain?
- Mood
- Anxiety
- Appetite
- Sleep
- Sexual function
How do presynaptic autoreceptors work?
- Neurotransmitter activates the receptor by binding to an extracellular site on the receptor
- Neurotransmitter cannot enter the neuron through an autoreceptor
How do re-uptake sites work?
- Neurotransmitter is transported back into the neuron
What are the effects or reserpine on monoamine synapses
- Reserpine causes monoamines to leak out of vesicles
- Monoamines are broken down by monoamine oxidase before it can cross the synapse
- When the presynaptic neurone is activated there is no neurotransmitter available for release
What is the monoamine hypothesis of depression?
- Major depression is due to a decrease in function of the monoamine system
- Low levels of available 5-HT or NA
What is tryptophan?
- Precursor of 5-HT
- Amino acid normally available in the diet
Tryptophan depletion study
Delgado et. al (1990)
- Took depressed patients currently on medication and symptom free
- Made them have a tryptophan-free diet for 2 days but also made them have a drink with a higher concentration of other amino acids e.g. protein
Tryptophan depletion study: Results
Delgado et. al (1990)
- Due to competition across the blood brain barrier the other amino acids are taken into the brain resulting in low levels of tryptophan
- Decrease in 5-HT
- Symptoms of depression re-occurred
- Once tryptophan was returned to the diet, symptoms went away
How do drugs work to increase 5-HT
- Originally monoamine oxidase inhibitors which block the breakdown of 5-HT
- 2nd and 3rd generation were re-uptake inhibitors which leaves more 5-HT in the synaptic gap
What is the time-lag effect of drugs?
- All classes of antidepressant drugs increase 5-HT levels immediately (within hours)
- Clinical response to drug treatment takes 3-5 weeks
What are the differences between NA and 5-HT neurons with chronic drug treatment?
- Some re-uptake inhibitors act at NA synapses as well as serotonin synapses (SNRI)
- For either system, autoreceptors become less responsive
- For 5-HT: decrease in postsynaptic receptors, but they become more sensitive
- For Noradrenalin: decrease in postsynaptic receptors and they become less sensitive
What are the long term effects of drug treatment
- Drugs like prozac rebalance the system
- Restore 5-HT and NA levels to normal through adaptive processes in postsynaptic receptors
- 5-HT receptors increase in sensitivity
- NA receptors decrease in sensitivity
- Both 5-HT and NA: downregulation
What is the stress hypothesis of depression?
- Chronic stress leads to depression
- Because of increased HPA activity there is more cortisol in the body
- Diminished negative feedback through loss of glucocorticoid receptors
What is the role of CRH
- Coordinates the stress response
- Increases NA (locus ceruleus)
- Released in limbic (emotional) brain regions
- Injection of CRH increases fear and anxiety responses in animals
- Too much CRH leads to imbalances noradranergic system, which puts the brake on 5-HT and reduces mood
