Posted by linkadge on March 14, 2016, at 19:35:00
In reply to Re: methylation hypothesis » linkadge, posted by SLS on March 14, 2016, at 13:21:28
Hi SLS,
From what I read, many antidepressants and mood stabilizers can counteract the effects of the hypermethylation in a certain brain region. For example, in schizophrenia there is a hypermethylation in the prefrontal cortex, which reduces expression of the reelin gene and gad 67. This would be expected to reduce connectivity and gaba levels in the prefrontal cortex. In animal models, valproate can reverse the changes to reelin and gad67.
From what I read, HDAC comes in different forms, depending on the location in the brain.
Some antidepressants can directly reduce the methylation in a widespread manner (ie amitriptyline) others inhibit HDAC which, can reverse some of the effects of the hypermethylation.
In one article I read, a common targets of antidepressants was to induce H7 acetylation in the nucleus accumbens, which functionally blocked the hypermethylation in this region induced by repeated social defeat. Animals that were resistant to the social defeat, didn't exhibit the hypermethylation. I am assuming the hypermethylation, functionally supresses activity of that particular region.
Like you say, hypermethylation of BDNF or the serotonin transporter are also present in some models of depression. This may be why SERT and BDNF are usually diminished in depression.
What I don't know, is whether "methylating agents" would functionally increase gene methylation in a nonspecific fashion.
How does this improve depression? Is it enhanced methylation of certain 'bad regions' aka increasing methylation of stress response systems might reduce stress reactions (?)
But yes, to answer your question, from what I have read, antidepressants and mood stabilizers (including lithium) tend to decrease gene methylation.
Linkage
poster:linkadge
thread:1087015
URL: http://www.dr-bob.org/babble/20160306/msgs/1087140.html