Friday, April 06, 2007

VEGF: the New antidepressant


Vascular Endothelial Growth Factor (VEGF) stimulates the growth of new capillaries. In the brain, VEGF also stimulates the growth of new brain cells. A recent PNAS article, by Jennifer L. Warner-Schmidt and Ronald S. Duman from Yale, demonstrates that VEGF is a middle-man in the antidepressant response mechanism (better abstract here).

They show in rats that:


  • VEGF goes up with ECT, with an sSRI (fluoxetine/Prozac), and with an sNRI (desipramine/Norpramine)

  • This increase in VEGF is associated with new neuronal growth in the hippocampus

  • Treatment with ECT, fluoxetine, or desipramine is associated with new neuronal growth in the hippocampus

  • Injecting VEGF is associated with an antidepressant response in animal models of depression

  • Blockade of the VEGF receptor with Flk-1 blocks the growth of new neurons in the hippocampus (in all 4 experimental arms--ECT, fluoxetine, desipramine, or VEGF injection)

  • Blockade of the VEGF receptor blocks the behavioral response to ECT, fluoxetine, or desipramine in animal models of depression
This study adds to the weight of evidence that one of the end results for antidepressant treatment is stimulating new brain cell growth. It is not clear whether this is related or not to these drugs' effects on serotonin or norepinephrine, but it appears it may be possible to bypass neurotransmitter mechanisms (and avoid their subsequent side effects) and go directly to neurogenesis. This may lead to some entirely new treatments for depression and bipolar disorder down the road (way down the road).

10 comments:

Parked said...

Sounds like this might be in some trials in the near future. I know quite a bit about new treatments and trials. You are right that this might be an option many years from now. A long, slow process is ahead. And when the word "speculate" is in any article, the process of getting it from an idea to the patient takes even more time.

Midwife with a Knife said...

Stupid question: Do depressed people have reduced number of neurons or neuronal death in their hippocampusus (hippocampi?)

patientanonymous said...

I like seeing stuff like this. It gives me hope about neuronal regrowth and neuroplasticity. You're right, it may be a long way down the road but at least people are still looking and not giving up.

Sarebear said...

Cool BEANS!

Wait, beans are a legume, not a veg.

Cool CARROTS! (Happy Easter!)

Or, as my dd has taken to saying w/no disrespect intended . . .

Happy Keister!

Roy said...

Midwife (no question is stupid)...
European J Neurosci 2001: No difference in postmortem hippocampi of depr and nondepr humans.

J Neurosci 1999: Duration of depression correlated with hippocampal volume loss.

Biol Psychiatr 2004: Reduced hippocampal volume, and increased cell density, in depressed subjects.

Uhh, I don't know the answer but these are places to start. Let us know if someone can synthesize the latest poop.

Sarebear said...

If you want synthesized poop, try some of those journals and such made out of processed Elephant dung.

Yeah, OT. I think this (not the dung, but the subject of the post) is interesting, although I still feel FAT everytime I see the hippo part in there. Lol.

Midwife with a Knife said...

Ah, thanks Roy. Trust me, there are stupid questions. (Such as, from my brother, "My auto emergency kit comes wiht flares; can you help me think of something fun to do with them? Um... how about keeping them in your car in case you need them?")

It looks like the answer is "Maybe not, but maybe...". :) I was just thinking that if the hippocampus in people with depression is normal, then making more neurons grow there may have unforseen negative long-term effects. But if, the hippocampus is not-quite-normal, then additional neuronal growth might be exactly what people need.

Or maybe the actual lesion is somewhere else, and making people grow more hippocampal neurons (hipponeurons?) allows their brains to compensate in different ways.

Sarebear said...

Hey, MWWK, I'm now picture hippo-neurons hippity hopping around in my brain . . . .

Dancing hipponeurons . . . ala the dancing hippoballet in Fantasia . . .

Woohoo, it's like being high, without the drugs (never done drugs, but when describing one particularly manic episode, my ologist said I was high; when I described that I quit feeling guilty about feeling so frickin' AWESOME and just laid back and enjoyed it and floated away.)

Anonymous said...

Isn't VEGF associated with cancer? As in increased levels are associated with certain cancers and a lot of the biological *mab drugs aim to block VEGF?

Anonymous said...

As a newly diagnosed cancer patient, I am very interested in the question about antidepressants VEGF and cancer. I have been taking Cymbalta for the last 4 years and now I suddenly have cancer, liver hemangiomas, and a proliferation of non-cancerous colon polyps--all conditions driven by VEGF.
Has anybody seen research that directly looked at whether Cymbalta or other antidepressant usage could fuel cancer angiogenesis?

VEGF and anti-depressants
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1838655

liver hemangiomas
http://www.ncbi.nlm.nih.gov/pubmed/18814928

intestinal polyps
http://mcr.aacrjournals.org/content/5/12/1296/F6.expansion

breast cancer
http://www.researchvegf.com/researchvegf/tumors/breast/index.m