Bipolar Flashcards
How does depression in bipolar disorder compare to depression in MDD
similar
Describe the biological theory of mania
what should be noted?
similar to model of monamine dysregulation in depression, but in the opposite direction for mania
this is a very simplistic way of looking at it
What do treatments of mania do?
Reduce or stabilize monoaninergic regulation of circuits associated with symptoms of mania
How big a role does gentics play in bipolar? what is the evidence of this?
larger genetic component
risk in relatives:
monozygotic twin 40-70%;
first degree relative 5-10%;
Unrelated person 0.5-1.5%.
What is the Norepinephrine (NE) Hypothesis of Mania?
Support?
Caution?
Low NE causes depression
High NE causes mania
Evidence for this is that
-> most NE enhancing meds can induce mania
Caution -> because drugs that increase dopamine and serotonin can also cause mania
Which antidepressants have the highest risk of enducing a manic episode?
SNRI
What is the Dopamine (DA) Hypothesis of Mania?
what is the evidence for this?
Some argue that too much dopamine is what’s driving bipolar disorder
- evidence that there are fluctuations in DA levels receptor levels
- people in manic episodes can experience symptoms of psychosis
- D1 receptor blocking antipsychotics also treat mania
What is the GABA Hypothesis of Mania?
Dysregulation of GABA:
- too much activity leads to slowing down brain activity
- too little activity leads to mania and/or anxiety
What is the Kindling Hypothesis of Mania?
repeated subthreshold neuronal stimulation causes action potentials
- the more stimulation you have in that part of the brain the more likley to have seizure, which susequently does damage and reduces the threshold for the next seizure
- > hypothesis borrowed from theories of epilepsy
What is the The “inositol” theory of bipolar disorder?
What supports this hypothesis?
most modern way of looking at bipolar disorder (pulls together the other theories)
inositol is a secondary messenger of NE and DA, and it is produced in response to stressors
- theory is that in bipolar disorder there’s an inability to shut off inositol which puts neurons in the brain in an arousal state which results in the death of neurons
evidence: Lithium seems to inhibit inositol
what proportion of time is spent in depression vs mandia
2/3 = depression
1/3 = mania
What we trying to achieve when treating bipolar disorder
need to treat the acute manic and stabilize ‘treat from above’
need to also treat acute depression and stabilize ‘treat from below’
but also to prevent future acute episodes
What is the proposed mechanism of action of lithium?
- Inhibits enzyme inositol monophosphase -> an enzyme that allows for the production of inositol
- Modulates G proteins, regulates gene expression of growth factors and neuronal plasticity by inhibiting downstream gene expression (prevent cell death)
but our understanding of the mechanisms of action of these drugs is lower than for others
What is Lithium effective for?
Indications
– Mania associated with bipolar disorder
– Maintenance treatment of bipolar disorder
– Bipolar depression and (in lower doses) treatment
resistant depression (but not as good as some of the other medications for this)
What is the main issue with lithium?
it is very toxic and has a narrow therapeutic index
blood levels need to be monitored closely
can result in weight gain, affect lipids and blood glucose + lots of other negative effects
Category D for pregancy (known negative effect)
