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Re: More evidence of inflammation and depression. » SLS

Posted by SLS on January 2, 2013, at 19:06:43

In reply to Re: More evidence of inflammation and depression. » Emme_V2, posted by SLS on January 2, 2013, at 17:46:40

> Hi Emme_V2
>
> When you have a chance, can you excise and quote the passages that you believe are proof of directionality?
>
> I still don't see it.

Perhaps I haven't made myself clear. I believe that, once established, major depressive disorder (MDD) can produce inflammation, which then contributes to the the worsening and persistence of the disease. It should be expected that there will be findings that describe the mechanics behind inflammation producing depression, otherwise my scenario wouldn't work. So far, everyone has been focusing on how inflammation might cause depression. I haven't seen any efforts made to evaluate how depression might cause inflammation. Depression causes cell damage and cell death through excitotoxicity, why would these events not provoke an immune response? They in fact, do. Microglial activation is the mechanism involved here, as this provokes the release of proinflammatory cytokines. What's more, intact neurons have a suppressive effect on inflammatory processes. Dead neurons provoke them.

I think there is an interplay between depression and inflammation. Each does not exist in a vacuum, and their contributions to the evolution of MDD are not mutually exclusive. It will take elegant study designs to tease out cause and effect. Such a study might look like this:

http://onlinelibrary.wiley.com/doi/10.1111/j.1528-1157.1998.tb01911.x/abstract

"Conclusions: In the kindling model of epilepsy, neither DNA fragmentation nor immune responses were detected. The result indicates that epileptic seizures do not depend on the immune responses. In the KA-treated model of epilepsy, immune responses were closely related to DNA fragmentation, suggesting an association of immune responses with neuronal death. We therefore suggest that immune responses play an important role in the neuronal death process induces by KA"

Robert M. Post and others have suggested that the progression of MDD and BD operate according to a kindling model. It is no mistake that I use this study to demonstrate directionality. Seizures do not depend on inflammation, but they do cause cytotoxicity and cell death. Cell death then provokes inflammatory responses. Inflammatory processes provoked by microglial release of cytokines causes even more cell death. My guess is that a resultant sclerotic scaring of tissue focally makes the epilepsy worse.

For now, I suspect that the induction of MDD does not require inflammation.

Does inflammation promote depression? Yes.

Must inflammation exist before MDD evolves? My guess is no.


- Scott


Some see things as they are and ask why.
I dream of things that never were and ask why not.

- George Bernard Shaw

 

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