Science on depression?
August 20, 2013 7:57 AM   Subscribe

What do scientists currently understand about depression? How, broadly, is this problem formulated as a subject of study? What are various scientists' opinions on the existing treatments, such as medical versus nonmedical approaches? What is the degree of consensus on these various issues, e.g. different schools of thought? What areas or aspects of it are still being poorly addressed?

I am interested in scientific resources on depression—i.e., necessarily theoretical and empirical understanding of critical, fundamental issues. While public and institutional policies and recommendations of the medical/pharmaceutical establishment are contributing voices, these depend on scientific evidence and insight. What is the best literature is available for non-experts to understand better this most common form of mental problem?
posted by polymodus to Science & Nature (10 answers total) 29 users marked this as a favorite
I'm not super well-versed in the latest research, but one of the best recent articles in the popular press I've read was this one in the NYTimes by Siddhartha Mukherjee (who is the author of the book The Emperor of all Maladies).
posted by Asparagus at 8:47 AM on August 20, 2013 [2 favorites]

This is a hard question to answer.

As far as I know, the science on MDDs (major depression disorders) is a bit all over the place, because depression is a human phenomenon and human trials are difficult to gather concrete data from in general. It's problematic to get congruous data from humans, generally because of the wildly differing variables, and particularly in depression because of the inability to adequately/accurately measure brain chemicals.

I do know that they have linked depression into lack of serotonin in the brain. And that most anti-depressants are actually reuptake inhibitors for serotonin, and work by increasing levels. Studies show that SSRIs have often worked in helping people with depression.

But I also know that some studies have shown that things such as Omega 3s may benefit those with MDDs-- but not if they have anxiety.

The consensus is that, scientifically, we know very little about what causes depression, and a lot of theories are not proven. Even studies that have correlations, have studies that have conflicting opinions. For example, the serotonin theory is challenged by findings that elevated serotonin levels occur in certain people with MDDs. So not only do we have two conflicting theories, we have a situation where an SSRI (an anti-depressant that elevates serotonin) actually may be contributing to the thing it is supposed to be helping.

The best start, for a non-expert, is probably to look the biology of depression entry at Wikipedia. It addresses a lot of the critical fundamentals and scientific theories behind depression, and gives a good understanding of genetic, chemical, and environmetal factors believed to cause depression.
posted by Dimes at 8:48 AM on August 20, 2013 [2 favorites]

The short answer is that we know very little. We know the symptoms. We know it can be a deadly disease.

The best way to grasp just how confusing it is I think is to look at treatments.

We are kind of sure it has something to do with chemicals in the brain. Selective Serotonin Reuptake Inhibitors seemed to be effective, like zoloft or prozac. But, as it turns out, sometimes Dopamine or Norepinephrine reuptake inhibitors are sometimes the most effective for some people. Some drugs target, for example, norepinephrine and serotonin - SNRIs like Cymbalta or Effexor. Some target only norepinephrine, like Strattera. Some target Dopmaine and Norepinephrine, like Wellbutrin. Some, in fact, block monoamine oxidase, the enzyme that breaks down monoamines in the synaptic cleft, and target all three in a non reputake-inhibition way.

In fact, it seems that depending on the case, any monoamine neurotransmitter might be boosted to treat depression. Of course, there are time, as mentioned above, where elevated serotonin levels seem to be maybe be the cause of a person's depression.

A lot of experts in the field still hold that electroconvulsive therapy ("shock therapy") is still one of the most effective methods for treatment-resistant depression. But the studies are conflicting.

Cognitive Behavioral Therapies work to actually shift thought patterns - actually rewiring parts of the brain through practice so that different synapse networks become habitual instead of intrusive or depressed thought-producing networks.

There's a lot of promising experiments being down with drugs like Ketamine and MDMA that seem promising. Drugs like MDMA produce increased serotonin from several nuclei and ongoing treatment with MDMA may prove more effective than SSRIs.

So the short answer is we don't actually know much, except more brain chemicals seem to help it.
posted by Lutoslawski at 12:13 PM on August 20, 2013

Andrew Solomon's The Noonday Demon is as good a place as any to start.
posted by munyeca at 2:25 PM on August 20, 2013 [2 favorites]

The root of depression is not well understood. Re: the idea that more brain chemicals seem to help it, there is some evidence for that, though there's also the argument that when people respond to SSRIs they are having placebo responses (for more on that, read Irving Kirsch, who wrote "The Emperor's New Drugs."

The Harper's essay "Manufacturing Depression" speaks to some of your questions as well, though also from an SSRI-skeptical point of view.
posted by feets at 3:30 PM on August 20, 2013 [1 favorite]

For example, the serotonin theory is challenged by findings that elevated serotonin levels occur in certain people with MDDs. So not only do we have two conflicting theories, we have a situation where an SSRI (an anti-depressant that elevates serotonin) actually may be contributing to the thing it is supposed to be helping.

I think the theory is that some people have trouble with fluctuating levels. That's why tienapine (or something like that) also works for some depression. It's a SSR-Enhancer, so it does the opposite. Instead of bringing the level up and keeping it there, it brings it down and keeps it there.

The big problem with depression (and lots of other diseases) is that the organics and the cognitive processes work with or against each other. A bad attitude can make depression more likely, and also harder to cure. But that's not necessarily a cause, just a complicating factor, or something that moves the margins a bit.
posted by gjc at 5:11 PM on August 20, 2013

One hour with Robert Sapolsky discussing depression. I highly recommend it.
posted by ovvl at 7:03 PM on August 20, 2013 [5 favorites]

Two discoveries in the 1950's were hugely influential in shaping the current scientific understanding of depression.

Reserpine, an antihypertensive that depletes monoamine levels, was found to increase rates of depression and suicidality. Iproniazid, a tuberculosis drug that inhibits monoamine degradation, was found to decrease rates of depression and suicidality.

Together, these two discoveries suggested that depression resulted from deficiencies in monoamine transmission—particularly that of serotonin and norepinephrine. It's hard to overstate how revolutionary this shift in thinking was at the time; the idea that a condition like depression might have its origins in biochemistry, and that it might be treatable using medication.

The monoamine hypothesis has been the reigning theory for half a century now, supported by a whole aresenal of compounds that have been found to alleviate depression by increasing synaptic levels of serotonin (as well as sometimes norepinephrine and/or dopamine).

However, there are many problems with this theory. To begin with, the drugs alter monoamine transmission almost immediately, but symptom relief generally takes several weeks to manifest. It was found that this timecourse coincided with alterations in the levels of monoamine receptors—basically, the brain adapting to the proximal effects of the drugs. But it is not really clear why exactly this should alleviate the symptoms of depression.

And the fact is that, most of the time, it doesn't. The efficacy of antidepressants is really quite low. Generally, rates of remission are in the range of about ~30%. Better than placebo, but not by much. So clearly there are other factors involved. Various things seem to affect rates of depression—genetics, diet, sleep, social environment, etc—but none of them are sufficient to explain why some people develop depression and others do not. And while antidepressants aren't particularly effective, alternative interventions haven't proven themselves to be significantly better in randomized clinical trials.

An exception would be ECT. It is far and away the most effective form of treatment for depression. The benefits, however, are relatively short-lived, and both its adverse effect profile and its social stigma have made it undesirable for most patients. The mechanism of action for ECT is even more mysterious than that of antidepressants; the resulting seizure causes a whole mess of biochemical changes in the brain, and it's not at all obvious which ones are important, or why.
posted by dephlogisticated at 7:18 PM on August 20, 2013 [2 favorites]

I enjoyed Peter Kramer's book Against Depression; it's not as scientific as you're asking for, but it covers a lot of ground and has copious endnote references to scientific literature.
posted by hattifattener at 9:15 PM on August 20, 2013 [1 favorite]
posted by theora55 at 8:56 AM on August 22, 2013

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