What is Serotonin and what is it involved in?
Acts as a neuromodulator influencing the activity of a variety of neurons throughout the brain.
- Appetite
- Working-memory
- Hallucinations
- Mood (key)
- Sleep and Arousal
- Note: Sleep and arousal is modulated in NA too
Where is serotonin synthesized? How is serotonin synthesized and transported?
Raphe Nucleus
- Synthesized in cell body
- Transported to synapses to store
- Rapid release from synapse when ready to fire
How does drug affect serotonin receptors as compared to natural serotonin?
- Serotonin has many subtypes (different location with different effects)
- More than the others
- Drugs are more selective in that they only activate specific receptors.
Synthesis pathway of Serotonin?
- Tyrptophan
- Tryptophan hydroxylase - Synthesize enzyme
- Amino Acid in food
- Tryptophan hydroxylase - Synthesize enzyme
- Serotonin
- Monoamine oxidase - Breakdown enzyme
Some DSM Criteria of Depression (Synptoms - inclusion and exclusion)?
Some facts to know (Gender, Onset, Financial Cost, Genetics)?
DSM
- Do not include symptoms due to a general medical condition, mood-incongruent delusions or hallucinations
- High frequency and sustained depressed mood
- Clinically significant distress
- Not due to the direct physiological effects
- Not accounted for by bereavment [REMOVED]
Facts
- Women > Men
- Adolescent onset
- Huge financial cost (15b)
- Genetic and envornment is important
Grief and Depression: Explain the differences and the argument for grief?
- Grief produces similar symptoms but rarely produces cognitive symptoms of depresion such as self-esteem
- Was argued that it is important not to miss people with clinical depression just because the symptoms were associated with grief. (Should help regardless of the trigger)
- Excluded in the DSM criteria
What is proposed as a risk factor for depression?
Impaired serotonin function
How is serotonin linked to depression? 3 Evidences.
- Depressed patients
- Reduced serotonin receptors
- Correlated with severity
- Genetics
- Gene involved in serotonin transportation linked to increased risk
- Tyrptophan Depletion (TRD) studies
- Given all amino acid without tryptophan (serotonin building block)
- Induce transient depressive symptoms
- Given all amino acid without tryptophan (serotonin building block)
Explain the risk factor of depression and how serotonin is linked to stress.
- Depression 5-6x more likely after stressful events
- Stress increases cortisol
- Serotonin important in managing feedback control of stress
Give an example of a SSRI and how does it function?
Prozac.
Blocks reuptake of serotonin (akin to cocaine on DA).
How long does SSRI take to see an effect? What does it imply?
- Very slow acting, takes weeks for effects
- Reaches brain after 1 hour post-consumption
- Improved mood NOT from direct serotonin increase around synapse
What are some theories explaining SSRI long-latency on mood?
- Altered gene expression
- Shuts pathologically elevated stress response
- Increased neurogenesis levels
Theory of SSRI long-latency on mood: Describe the Altered gene expression.
Altered gene expression
- Leading to slow changes in the action of different processes
- within a neuron (neurotransmitter synthesis or storage)
- or structure of the neuron (synaptic remodeling).
Theory of SSRI on mood: Explain how it Shuts pathologically elevated stress response.
Shuts off a pathologically elevated stress response underlying depressive symptoms, allowing for important neural adaptations.
Theory of SSRI on mood: How does it increase neurogenesis levels?
Increased levels of neurogenesis (birth of new brain cells) change or strengthen important mood related circuits in the brain.
New evidence suggest SSRI’s could promote new brain cell growth treating past damage and may even be “neuroprotective”, protecting against future damage associated with depression.
What does it mean that SSRI is “neuroprotective”?
Protecting against future damage associated with depression
Does SSRI alter personality? How? In clinical and healthy controls.
SSRI (Prozac specifically) alterns mood and personality in both
- Clinical
- Reduce depressive symptoms
- Healthy
- Increase empathy and prosociality
How does MAOI function?
Blocks monoamine oxidase (MAO)
Blocks the breakdown of serotonin
is MAOI safe?
- Can lead to lethal levels of serotonin if ingested orally after eating too much Ttyptophan or Tyramine (amino acid for DA/NA)
- “Cheese Syndrome”
- Used as a last resort under strict conditions.
