Sunday, November 01, 2009

Rethinking Antidepressants

Thanks to Henry for sending this link.

On cnet news, Elizabeth Armstrong Moore writes about research presented at this month's Neuroscience conference in Chicago:

Depression researcher Eva Redei presented research at the Neuroscience 2009 conference in Chicago this week that calls into question two tenets of depression science: that stressful life events are a major cause of depression, and that an imbalance in neurotransmitters triggers depressive symptoms.

Armstrong goes on to report that the research looks at the overlap of genes in RATS (not peeps) and notes that antidepressants work better for stress then depression and the genetic overlap between the two is minimal (--oh, why isn't Roy writing this, he's so much more eloquent than I am about the genetic stuff).
Armstrong goes on to say:

To test the long-held belief that stress is a major cause of depression, Redei looked for similarities between these two sets of genes. Out of more than 30,000 genes on the microarray, 254 were related to stress and 1,275 to depression. Only 5 were found in both samples.

"This finding is clear evidence that at least in an animal model, chronic stress does not cause the same molecular changes that depression does," Redei says. She is now looking at the genes that differ in the depressed rats so that she can narrow down targets for drug development.

Antidepressants are also often ineffective, Redei says, because they aim to boost the neurotransmitters serotonin, norepinephrine, and dopamine, whose reduced levels have been associated with depression. But this strategy is now also being called into question.

It's sort of news to me that we thought stress "causes" depression. I guess I thought extreme stressors (as opposed to general 'stress') can precipitate depression in those inclined to become depressed. Many people suffer extreme distress without getting major depression and many people with histories of major depression weather severe storms without a recurrence. What is nice about this research is that it challenges us to think in new ways, and I think sometimes research gets hooked around theories that aren't definitely proven and creativity gets stifled. Anything that nudges that can't be bad....


Anonymous said...

I'm tired of the theory that says raising neurotransmitter levels will not affect mood. This is obviously nonsense, as anyone who has used a drug of abuse can tell you that raising neurotransmitters will affect how you feel.

The problem is the assumption that 1) depression is ALWAYS a chemical imbalance and 2) serotonin is ALWAYS implicated in depression

I suspect "imbalanced neurotransmitters" are a cause of only a small minority of depression, and serotonin is rarely the problem. Serotonin numbs a person out, and it is highly effective for stress and anxiety (some types) but it isn't really a mood booster, and some typical symptoms of true depression (lethargy lack of motivation fatigue) often get worse.

I agree with the idea, though, that most antidepressants target stress as opposed to depression. No problem, most cases of depression are actually stress.
Now adays "feeling bad" is depression... much in the way "feeling agitated" has come to be mania. Ridiculous.

Anonymous said...

i've suffered from major depression at least since i was 10. i've found there are triggers for my acute depressive incidents, although i'm unclear whether or not chronic depression is always present at the time the spikes occur.

example: i just found something out about someone i hadn't seen in many years and how they blamed me for something that they were responsible for.

my thoughts have been running around in circles about this since then: anger, guilt, more anger cause it wasn't my fault, more guilt cause i'm just programmed to feel guilty about everything, anger, defeat, ... ad naseum.

(now that i put this down, i realize that, yes, i have had a low-grade chronic depression for many months.)

i have a couple of questions about those thinking circles.

1) is this what i've seen referred to as "ruminating"?

2) when the medical profession uses ECT treatment on depressed people, are they trying to break these circles? (i've heard they shock you till you forget why you're depressed.)

3) is there a better way to talk about these thoughts with other people than to say "i've been talking to people who weren't there"?

moviedoc said...

We all know that when something bad happens it makes us feel bad. Is that not normal? A Major Depressive Episode is an illness, not normal.

The issue of "causality" is complex. Didn't clinkshrink talk about the legal definition from the AAPL mtg?

Kenneth Kendler in Richmond says we should not talk about cause until we elucidate mechanism. I agree 100%.

And yet every day I see expert witnesses say some event (usually with $$$ attached) "caused" a Maj Depressive Episode or treating professionals making the same error. Often the best basis for such a claim is post hoc ergo propter hoc.

Bottom line is we do not have a way of determining what caused a Major Depressive Episode.

Anonymous said...

Maybe this is a stupid question, but how exactly do you determine whether or not a rat is depressed to begin with?

Sarebear said...

I'm all for studying any and all aspects of depression, and antidepressants, and/or challenging possible assumptions that may or may not have been made in the past about how things work.

I am getting just a little tired of the trial and error process; this last "error", much of which I consider to have been UNsupervised by the half-assed psychiatrist I'd been seeing, almost killed me several times; do you know how many times I came a breath from taking all my sedating meds and combining with a plastic bag over my head? In the time I was on that stupid med that I never would have credited before this last week with how long and hard it wore me down and caused types of thoughts and feelings . . . . ME, who was raised pretty much on ideas of choice and accountability, free agency, our own ability to judge and choose, I never would have said before last week that a med could have done that to me for so long, but it did, and I'm angry, because I was essentially unsupervised with a history of an initial dangerous reaction on that med that he never followed up on after the initial pressure cooker intensity cooled down a bit. NEVER. I was left thinking it was ME, all spring and summer and fall.

He's a damn stupid hippie idiot who never answers his phone and I hate him. I hate him for what he did to me and I hate this med for what it did to me and at the moment I despair of ever finding an antidepressant that works . . . . . .

but I also know, as the more rational side of me kicks in, that trial and error is the best our medical system can do, altho I'd hope the next shrink, should I get over my nausea at the idea and find one, a decent one, would give me better care than this last one, because I deserve better care . . .

Don't I?

Hopefully my GP will agree to maintain my mood stabilizer, add, and one other basic med that I've done well on, until a mental health professional can be found.

But studies such as this are essential if we are ever going to get the trial and error part of things down to a little bit more of a scientific process, perhaps . . . . . .

Anonymous said...

Very late to the discussion, but from personal experience, your suggestion that stress does not cause depression but can trigger it is very true.

What I keep asking myself when I read about research like this is, who decided depression was, in itself, an illness? It has felt to me more of a symptom, like pain. The same symptom can have multiple causes, right? You can't find genes for pain, can you?

Along the same lines, I don't really care how SRIs work. What matters is that, for me, they have helped (along with therapy) make the pain go away.

moviedoc said...

As a terminology nut I like what anonymous says: depression is the name of a mood state. Illnesses which generally manifest depressed mood include major depressive disorder and dysthymic disorder among others.