Neurotransmitter changes in disease

[elegantorchid]

Hi I'm reviewing psychiatry pathology right now in FA and I'm somewhat confused with the NT changes. They don't really make much sense to me. I never really dug into it during school year but I figured now is the time to make sense of stuff.

Can anyone make sense of the chart on page 503 of FA2014? Some of the disorders and their associated NT changes make sense but others not so much.


Parkinson Disease: increase 5-HT
What does 5-HT have to do with Parkinsons? I view 5-HT as sort of a happy/calming NT hence using SSRI with depression.

Huntington Disease: decrease ACh
ACh helps you move so I would have expected that to increase not decrease.

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[sadaca]

Yea I was wondering too esp the serotonin for parkinsons

 

[oingoboingo]

I am not sure about the Parkinson's situation, but for Huntington's - lose Ach signaling in the caudate which is inhibitory - so get less motor inhibition. Yes? No?

 

[elegantorchid]

ah great ok. well now we just have to explain the reasoning behind serotonin.

In general I seem to get the impression that medications for CNS stuff doesn't make much sense based on their mechanisms of action which is really annoying.

 

[aussiemedico]

I had the same question on this page in FA... any luck with the serotonin in Parkinson's? also, why is acetylcholine increased in Parkinson's?

Regarding Huntington's and ACh, I think that they're alluding more to the later stages of the disease... Robbins says that small/medium neurones are affected first, particularly the medium GABAergic striatal cells. As the disease progresses, ACh cells are lost which leads to the dementia and behavioural disturbances (notice that in both Huntington's and Alzheimer's you have less ACh... some have even proposed using acetylcholinesterase inhibitors as symptomatic treatment in Huntington's although there isn't evidence for it at this point).

 

[notbobtrustme]

unless you want to get nitty gritty, don't worry about it. Just memorize the table and realize some things just are.

FWIW, there's only a few questions in Uworld that touch on this and the questions are all answerable from that single chart in FA. After doing a couple NBMEs, I think there was exactly 1 question on this topic and it was answerable straight from that table.

 

[aussiemedico]

I just like understanding why things are the way they are so that they're easier to remember :/ If anyone has any ideas, please let me know. Thanks!

 

[aussiemedico]

One of my pharmacist friends just helped me out with this... from Rang and Dale re PD and ACh:

"For more than a century, until levodopa was discovered, atropine and related drugs were the main form of treatment for PD. Muscarinic acetylcholine receptors exert an inhibitory effect on dopaminergic nerve terminals, suppression of which compensate for a lack of dopamine. "

Also, regarding both acetylcholine and serotonin in PD, apparently newer atypical antipsychotics have fewer extrapyramidal symptoms because they have both anti-muscarinic and anti-serotonergic effects, which leads to less inhibition and of striatal dopaminergic cells. This would likely be the mechanism involved in PD as well!