Psycho-Babble Medication Thread 713163

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Glucocorticoid receptor hypothesis of depression

Posted by dessbee on December 13, 2006, at 5:14:51

Found some interesting articles about reduced glucocorticoid receptor densisty in mice causes depressionlike behaviors,
HPA axis dysfunction and decrease in BDNF when exposed to stress.

This may be critical in the pathogenesis of depression, since glucocorticoid receptors inhibit release of CRH.

http://www.physiology.emory.edu/FIRST/pdfs/Neigh_Nemeroff_2006.pdf

http://www.biopsychiatry.com/glucocorticoidreceptor.htm

Another study shows how dynamic the glucocorticoid receptor density is.
Neonatal handling resulted in increased hippocampal glucocorticoid receptor density, which implies an increased HPA axis sensitivity.
Results also showed that handling increased BDNF.

http://bmc.ub.uni-potsdam.de/1744-859X-4-8/


 

Re: Glucocorticoid receptor hypothesis of depression » dessbee

Posted by Quintal on December 13, 2006, at 14:57:44

In reply to Glucocorticoid receptor hypothesis of depression, posted by dessbee on December 13, 2006, at 5:14:51

>Another study shows how dynamic the glucocorticoid receptor density is.
Neonatal handling resulted in increased hippocampal glucocorticoid receptor density, which implies an increased HPA axis sensitivity.
Results also showed that handling increased BDNF.
>

So this suggests babies that are handled, massaged and stimulated more have a higher resilience to stress etc?

I think I've read something similar to this before. Interesting. Makes sense that babies that are neglected often develop problems like depression and low stress tolerance as adults.

Q

 

Re: Glucocorticoid receptor hypothesis of depression » Quintal

Posted by Maxime on December 13, 2006, at 22:06:05

In reply to Re: Glucocorticoid receptor hypothesis of depression » dessbee, posted by Quintal on December 13, 2006, at 14:57:44

> >Another study shows how dynamic the glucocorticoid receptor density is.
> Neonatal handling resulted in increased hippocampal glucocorticoid receptor density, which implies an increased HPA axis sensitivity.
> Results also showed that handling increased BDNF.
> >
>
> So this suggests babies that are handled, massaged and stimulated more have a higher resilience to stress etc?
>
> I think I've read something similar to this before. Interesting. Makes sense that babies that are neglected often develop problems like depression and low stress tolerance as adults.
>
> Q

Would explain me.

But people can still respond to touch as a way of healing. It's not too late for some. I've heard it's helpful for anorexia.

Maxime

 

Re: Glucocorticoid receptor hypothesis of depression » Quintal

Posted by dessbee on December 15, 2006, at 8:36:32

In reply to Re: Glucocorticoid receptor hypothesis of depression » dessbee, posted by Quintal on December 13, 2006, at 14:57:44

It is interesting that Glucocorticoid receptor expression/density can be manipulated by handling.
One can also speculate in the possiblity of social inheritence for depression, but I think we have to be careful blaming our parents since by the time we realize that they can be partially blamed it is too late to ask them to fix it. There is also the possibility that they will blame their parents, like a viscous cycle passed on from generation to generation - what comes around goes around.

The studies on poor handling really shows how socially dependent/ineractive we are. When family/society can not provide good handling it may result in poor stress resilience.

But the etiology behind depression is probably more complicated. Many children dealing with poor handling grow up surviving it without depressions. Some children seems more vulnerable to poor handling than others so there must be genetics involved causing a dysfunction in the HPA-axis. This would really show how genetics and environment acts together causing the depression. Maybe when we understand the mechanism that can increase the Glucocorticoid receptor density, we will be able to cure depression at its core. When that day comes maybe we will stop blaming our parents ;-)


 

Re: Glucocorticoid receptor hypothesis of depression

Posted by dessbee on December 15, 2006, at 8:40:30

In reply to Glucocorticoid receptor hypothesis of depression, posted by dessbee on December 13, 2006, at 5:14:51

It is interesting that animal models show that low glucocorticoid receptor density in the forebrain produces depression-like changes in adrenal axis regulation and behavior. Cortisol is a Glucocorticoid receptor agonist and act on these receptors to inhibit CRH release. So low glucocorticoid receptor density makes HPA-axis less sensitive and more cortisol is needed for feedback inhibition. Depression is like a thermostat gone haywire initiating a stress cascade.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=544280

Here are some pictures explaining the HPA-axis:

http://www.biology.ucr.edu/people/faculty/Garland/HPA_axis.jpg

http://cti.itc.virginia.edu/~psyc220/kalat/JK367.fig12.6.HPA_axis.jpg

 

Re: Glucocorticoid receptor hypothesis of depression » dessbee

Posted by Quintal on December 15, 2006, at 10:58:45

In reply to Re: Glucocorticoid receptor hypothesis of depression » Quintal, posted by dessbee on December 15, 2006, at 8:36:32

Not sure what you are referring with regards to parental blame. I've reviewed my original post and there was no suggestion of that as far as I can see.

As you say, the genes and environment are interdependent and work together to determine the stress resilience of the individual. There are children who are eager to blame their parents for their every shortcoming, and likewise I imagine there are many parents who would like to blame genes to excuse the result of their poor parenting ;-)

Q

 

Re: Glucocorticoid receptor hypothesis of depression » Quintal

Posted by dessbee on December 15, 2006, at 11:23:37

In reply to Re: Glucocorticoid receptor hypothesis of depression » dessbee, posted by Quintal on December 15, 2006, at 10:58:45

It strikes me that this hypothesis may explain why psychotherapy may work for some depressions, it is handling on a communicative/emotional level.

I wasn't referring to you blaming parents, I was referring to the possiblity of social inheritence being the cause of depression.


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