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Can epigenetics help beat depression?

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From The Scientist :

Antidepressant Exerts Epigenetic Changes

“Depression is considered a stress-related disease and it has been known for a while that stress can change long-term behavior, probably by reprogramming gene activity,” said study coauthor Theo Rein of Max Planck. Several groups previously demonstrated that environmental factors could influence epigenetic changes associated with psychiatric disorders, including depression. Different classes of antidepressant drugs have also been found to induce epigenetic changes in both animal brain cells and in clinical studies. “In depression, we’ve seen alterations in gene expression that coincide with DNA methylation and other epigenetic changes,” explained Rein.

The present study builds on previous work suggesting that the activity of a protein chaperone called FKBP51—which is known to regulate the glucocorticoid receptor implicated in stress responses—is necessary for the efficacy of the antidepressant paroxetine. The researchers have now provided evidence that this drug can reduce the activity of DNMT1, a DNA methyltransferase that globally adds methyl groups throughout the genome.

Abel would like to know what effects, if any, these epigenetic alterations may have on behavior. What happens in the brain regions crucial for depression and the action of mood-altering drugs also remains to be explored. In an email to The Scientist, Joanne Ryan, a research fellow at the Murdoch Childrens Research Institute who studies psychiatric epigenetics, wrote: “The findings here are using human peripheral blood cells which are unlikely to reflect epigenetic mechanisms occurring in different brain regions.” More.

See also: Epigenetic change: Lamarck, wake up, you’re wanted in the conference room!

Here’s the Editor’s summary:

Antidepressants chaperone DNA methylation

Epigenetic changes are associated with depression. Some depressed patients have increased DNA methylation and decreased expression of the gene encoding BDNF, a secreted factor important for synaptic plasticity. Rein et al. found that some antidepressants inhibit epigenetic changes by causing a switch in chaperone binding to the DNA methyltransferase DNMT1. The chaperones FKBP51 and FKBP52 competed for binding to CDK5, a kinase that activates DNMT1. The authors found that cells from depressed patients or cultured mouse astrocytes exposed to the antidepressant paroxetine favored the FKBP51-CDK5 interaction, resulting in reduced activity of DNMT1 and DNA methylation, and increased the expression of BDNF. These effects of paroxetine on patient blood cells isolated before therapy correlated with a positive clinical response to antidepressants, suggesting that a simple blood test may aid in personalizing treatment for depression. (paywall) – N.C. Gassen et al., “Chaperoning epigenetics: FKBP51 decreases the activity of DNMT1, and mediates epigenetic effects of the antidepressant paroxetine,” Science Signaling, doi:10.1126/scisignal.aac7695, 2015

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3 Replies to “Can epigenetics help beat depression?

  1. 1
    Jack Jones says:

    Denyse, I am going to someday buy the book “The Spiritual Brain” that you coauthored, I have too many books to get through at the moment but I liked what I heard about it.

  2. 2
    Robert Byers says:

    I don’t agree depression is mysterious or based on chemicals in the brain. I see it as simply in a spectrum of memory malfunction by way of the triggering mechanism.
    I don’t think its accurate to say things change in the brain at all like in this study.
    Its about thoughts and not hard wiring.

  3. 3
    EDTA says:

    Just ran across an interesting study. The graphic here is particularly revealing. Seems depression may be a combination of numerous downward spirals, which is why it is so danged hard to beat…

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