It’s All in the Nerves: How to Really Treat Depression

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Exercise, Prozac and electroconvulsive therapy (ECT) may ultimately relieve depression in the same way.

That’s what the latest research, conducted on mice, suggests, and the scientists are encouraged that similar processes are at work in the human brain as well. According to the findings, published in the journals Cell Stem Cell and Molecular Psychiatry, all of these therapies can spur the growth of brain cells. And it seems that such neurogenesis, which perhaps results from changes in levels of brain chemicals like serotonin, can lift the symptoms of depression.

Since the mid-1990s, researchers have been piecing together a theory of depression that accounts for the seemingly disparate triggers of the mental illness, as well as the variety of treatments that seem to counteract the negative mood.

And so far, this is what they believe: extreme or uncontrollable stress, particularly early in life, can lead to excessive release of the neurotransmitter glutamate in the brain.  At these high levels, glutamate can damage or even kill certain cells in the hippocampus, a region known for its role in memory.  This can lead to a thinning of the neural network in this area, which contributes to depression for reasons that are not yet clear. But antidepressant treatments all seem to promote the birth of new brain cells in that part of the brain.

Moreover, “It’s not just growth of new nerve cells [in this region],” says Bruce McEwen, professor of neuroscience at Rockefeller University, “There’s also plasticity of nerve cells all over the brain  that is ongoing and can be facilitated or blocked.”  These changes may start in the hippocampus, where new cells can be born, but older cells can be revitalized elsewhere as well, perhaps even changing the circuit of nerve activity that keeps people stuck in depressive thoughts and feelings.

MOREAntidepressants: Are They Effective or Just a Placebo?

Now, Hongjun Song, professor of neurology and neuroscience at Johns Hopkins University, documents how disparate treatments, from exercise to antidepressants that manipulate serotonin levels, and even electrical stimulation of certain brain regions, can ultimately trigger this nerve growth that fights depression.

The brain must maintain a delicate balance, with complex chains of signals keeping various opposing processes in check.  One protein that stymies the growth of brain cells, sFRP3, is useful in controlling cell growth from getting out of hand, but could be harmful if it hampers necessary growth. Working with mice, Song and his colleagues showed that antidepressant medications, ECT and exercise all affect levels of sFRP3.

“If you treat with different classes of antidepressants or ECT, they all lead to changes in expression of sFRP3,” says Song, who studied Prozac (fluoxetine), a selective serotonin reuptake inhibitor (SSRI) and imipramine, an antidepressant in another class of drugs called tricyclics, which regulate multiple neurotransmitters.  The research showed that these drugs reduced levels of sFRP3 levels in the hippocampus, which allowed new cells and connections to grow.

To further confirm the effect of sFRP3 on depression, Song and his colleagues also genetically engineered mice without the sFRP3 protein; these animals were less likely to show depressive responses when they were forced to swim until exhaustion, an indication that they were less prone to experiencing the negative mood state.

The research also found that in human patients, genes associated with the protein affected how long it took depressed people to respond to medication. Taken together, the latest data suggests that presence of elevated levels of sFRP3 protein may increase vulnerability to depression by preventing new nerve cells from growing in the hippocampal region. Similarly, mice given ECT, and those that exercised regularly, also showed lower levels of sFRP3.

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So how do things as different as ECT, drugs and exercise change the same protein? They all affected a single type of cell in the hippocampus, known as granule cells.  “What matters is that you want to activate [these] granule cells,” says Song. “If the animals do running, that leads to firing of those neurons,” he says, explaining that all of the other treatments did so as well.

Further studies are needed to confirm whether consistently high levels of the protein increase the likelihood of depression in human patients, but if that’s the case, then activating granule cells, by way of suppressing the release of sFRP3, might be a promising new way of treating depression. So far, “no drugs are known [to affect it directly],” says Song, “The next step is trying to find an approach where we can modulate the function of sFRP3 as an antidepressant.”

47 comments
souzou_no
souzou_no

@TIME @TIMEHealthland clean up your act, get rid of bad habits and toxic relationships including shrinks, go on a "walkabout"find ur bliss

rlanzara
rlanzara

RT %s How to really treat depression | %sdux (v%san%sl%si%sogy

Tiffenii
Tiffenii

@docrocktex26 met a teenaged mom today suffering from depression AND anxiety. The doctor gave this child Xanax! My jaw dropped!

Peace_2_All
Peace_2_All

Interesting new development.  Let's hope that scientists' can now turn this into something useable and effective for the this debilitating disease.

Peace...

docrocktex26
docrocktex26

@Tiffenii Argh!!!! Physicians who inappropriately (read recklessly) prescribe Xanax are the bane of my existence. Don't even get me started.

Tiffenii
Tiffenii

@docrocktex26 well it's sad because even she was telling me she is scared to take it. That is all that she was prescribed!! Sad

Kbarmike
Kbarmike

%s lithium is naturally in the soil everywhere,it's absorbed slowly&steady,not only relieves stress, but pain,muscle aches! %s :)

Kbarmike
Kbarmike

@ASSTnews farmers, they absorb the lithium that in the soil naturally, that an they're busy 16-18hrs a day! :)

docrocktex26
docrocktex26

@Tiffenii That's great! Thank you for your advocacy, the only way we can effect change is to educate ppl on the issue; starting w\/doctors.

Tiffenii
Tiffenii

@docrocktex26 exactly! I just did a TV interview last month about teens abusing prescription drugs with Xanax being at the forefront.

docrocktex26
docrocktex26

@Tiffenii Frustrating b\/c it's not the standard of depression care for psychiatrists, but ppl more commonly see their GP for treatment.

docrocktex26
docrocktex26

@Tiffenii I see it far too often, it's a major problem and it's an absolute mess to clean up once it's been created.