Archive for: August, 2010

Back to Basics 3: Depression post 5, The Serotonin Theory of Depression

Aug 25 2010 Published by under Uncategorized

...and why it's probably wrong.

Ok, the serotonin theory of depression may not be wrong. But it is definitely incomplete. One might ask why we use serotonergic drugs to treat depression if the theory behind it is wrong. A good question, but to this I say: because it worked.


This is post four of my series on depression. For previous posts on the etiology of depression, the pharmacotherapies for depression, and how depression is evaulated in the lab, please play link hopscotch! I've also got a very recent post on the serotonin system which can give you some more background.

The original antidepressants, the monoamine oxidase inhibitors and tricyclic antidepressants, were originally used to treat other diseases, such as tuberculosis and psychosis, and found to be effective for depression as a sideline. Did people know how they worked? Nope, but they appeared to work (though only in a subset of the population), and so they came into use. Some people might get up in arms about this, and yell about how we shouldn't use drugs unless we know how they work. But if we spent our lives doing that, no one would have ever made asprin. Or morphine. Heck, no one would have patented Ritalin. We know THAT Ritalin works, and we know what Ritalin does in the brain, but do we know why Ritalin calms down people with ADHD when it's really a stimulant? Not really, no. But it's still out there, because it works.

And the serotonin-based antidepressants do work in some people. Only in about 60% of patients at best, and at their best, they only perform 30% better than placebo. But the modern selective serotonin reuptake inhibitors (SSRIs) still work in a set of depressed patients, and they do so with far fewer side effects than pre-existing drugs. And what can I say, we haven't really got anything better yet. Except cocaine. That's a GREAT antidepressant, but it obviously has some issues.
So where did this serotonin theory of depression come from? And why is it flawed?

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Back to Basics 3: Depression post 4, the SEROTONIN SYSTEM

Yeah, today's a big day, there's a LOT I've written on depression, but do not fret, we will get through it all!!!

You can't get through a whole day on depression without talking about some serotonin a little!

Hang on to your hats:



Oh yeah, she went there. Photo courtesy of The Loom blog from Discover. Sci might have to get one of these...

To begin with, I will admit that I do not know everything there is to know about serotonin. I am able to readily admit this because NO ONE knows everything there is to know about serotonin. This is not just because we haven't figured it all out yet, but also because the serotonin system is completely, insanely complicated. You perform a pubmed search for "serotonin system review" and you get 176 PAGES of citations, all of them on things like "the serotonin system and anxiety", "the serotonin system and cardiovascular effects", "the serotonin system and gastrointestinal effects", and the list goes on. To do a complete review of all that is currently known about the serotonin system would take hundreds of pages and probably thousands of citations. This is partially because serotonin not only does tons of things, but it does lots of stuff that has very little relation to any of the other stuff that is also doing. You can't really make any sweeping generalizations about serotonin, there are always exceptions to the rule.

So what I'm going to go into here will be what I know about serotonin, as general as I can make it, and not covering even a quarter of what there is out there. But it will hopefully give you an idea of what people are talking about when they talk about serotonin drugs, serotonin effects, etc.

So here we go.

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Back to Basics 3: Depression post 3

Welcome to depression post three, part of Back to Basics week at Neurotic Physiology!

Previously I covered the symptoms and etiology of depression, and some of the most common antidepressant medications and how they work. Now I'd like to go into some of the research behind it. After all, it's not like we just grab a depressed person and say "here, take this and call me in the morning". Every new drug that comes out on the market has to go through rigorous clinical testing to determine whether or not it works, and just as important, whether or not it is safe. And even then, drug companies and the FDA make mistakes.

This post (to save me writing another 2,000 words at a time) is going to focus on the way we study depression (along with other psychiatric disorders) using animal behavioral models, particularly rodent models. But of course, you can't put a mouse on a couch and ask it how it feels about its mother. What researchers have found is that there are ways of studying the efficacy of traditional antidepressants. So rodent tests for depression are not so much tests for depression so much as they are screening for possible antidepressant therapies.

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Back to Basics 3: Depression post 2

Aug 25 2010 Published by under Uncategorized

In my previous depression post, I talked about the symptoms and characterization of depression. In this one, I want to talk about what's out there to treat it.

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Back to Basics 3: Depression post 1

Aug 25 2010 Published by under Basic Science Posts, Behavioral Neuro, Neuroscience

Welcome to day 3 of Back of Basics Week! And it's Wednesday. Hump Day. The boring, most depressing day of the week (except possibly for Monday). What better day to get some basics on depression?

So here's the first one, the first in a trio of posts on clinical depression:

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Back to Basics 2: Neuroanatomy, part 3!!

Aug 24 2010 Published by under Basic Science Posts, Neuroanatomy

Welcome to part 3 of Sci's basic posts on Neuroanatomy, part of Back to Basics week!

Apparently everyone is very impressed by how hot my brain is (see parts one and two), but unfortunately, we're almost out of pics. Today we're covering the rest of the bits of my brain that look really awesome, which really boils down to all the ones you wouldn't be able to see if you were just looking at the outside. And it turns out that Sci has a LOVELY basal ganglia. She is thrilled by this, the basal ganglia is her favoritest part of the brain.

First, a note: those cross-hairs that you've been seeing all the time are features of the analysis program, apparently, and can't get taken out. Blah. But we shall forge ahead!


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Back to Basics 2: Neuroanatomy part 2!

Aug 24 2010 Published by under Basic Science Posts, Neuroanatomy

Welcome to basics week at Neurotic Physiology! This post covers part two of brain neuroanatomy, using Sci's OWN BRAIN as reference. Yes, I am awesome. I know.

Ok, so I thought I would be able to do this brain stuff in TWO entries, but I think it might have to be three. After all, the brain is a wondrous, glorious world of awesome, and MY brain in particular is especially nice. Last time I talked about the outer features of the brain and the division of the brain into traditional lobes of form and function. So today I'm going to give a brief intro to things with arcane sounding names, like dura mater and the choroid plexus, and talk about why it's ok that your brain is full of holes.

So let's begin!

The Maters


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Back to Basics 2: Neuroanatomy. Let's get started.

Aug 24 2010 Published by under Basic Science Posts, Neuroanatomy

As part of my Back to Basics week, one thing you'll want is an introduction to NEUROANATOMY. The brain ain't just a pile of unorganized grey matter, no indeed. In fact, it's really highly organized. Let's get started.

Some of you may recall that I got my brain scanned in an MRI for the sake of science. Well, my lovely fellow grad student was nice enough to send me some of my baseline pictures! I think I have a lovely brain (see my profile pic? I'm totally hot, right?), and so I thought I would share some of it with you. Besides, I blog a lot about basic (and not so basic) neuroanatomy, and so we can use hot pics of Sci's brain to give you some insight into areas of the brain that are popular in science today.

And just to scratch the surface:
Picture 10.png

I'll be dividing these posts into three parts, the first with general features and terms, and the second and third for some of the interior features that happened to come out really well on my scan.

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Back to Basics 1: Neurotransmission!

Aug 23 2010 Published by under Basic Science Posts, Neuroscience, Uncategorized

First in our back to basics series, a very important topic indeed. Neurotransmission is at the basis of everything you read about MRI, neural circuitry, how areas of the brain communicate...basically a LOT of neuroscience requires that you know something about neurotransmission.

I suppose I thought for a while that if I was talking about dopamine and serotonin and GABA and things enough, people would just kind of "get" neurotransmission. And most people do. But it's still a good thing to cover, partially because it's kind of mind boggling to think about (well, Sci finds it mind-boggling), and partially because it helps you understand why changes in receptors, changes in transporters, or changes in release will have different effects. This comes in very handy when talking about various psychiatric and addictive drugs of which I am very fond. And so, your general post today: Neurotransmission.

And also, I get to DRAW!!! w00t.

The synapse. Do not be fooled by its commonplace appearance. Like so many things, it is not what is on the outside, but what is on the inside that counts. 🙂

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24 responses so far

Back to Basics!

Aug 23 2010 Published by under Basic Science Posts, Uncategorized

Sci is so excited you guys. I am taking a VACATION. It's the first time in...more than three years, I think, where I am going someplace I have never been and using the time to do exactly what I want to do. NO WORK will be coming with me.

As much as I feel I've earned it, as a good little new post-doc, I can't shake the feeling that if I were REALLY devoted to science, I wouldn't be taking a week off. But you know what, screw that noise. I am kicking the guilt. I didn't even get a break between dissertation and post-doc, and I surely do need one.

So YAY! Mr. S and I are taking a WHOLE WEEK to fly to an undisclosed location far from our current undisclosed location. It's gonna be a good time.

And in the meantime, I decided to do a series of reposts. I get a lot of comments from friends of the blog that, even though I try REALLY REALLY hard to be simple on the blog and talk to people without much science-knowledge, I get complaints that I go right over people's heads. I'm very sorry, and I'm trying to be better. But there also comes a point where you're gonna have to meet me halfway. A lot of these subjects require a TON of background knowledge about things like neurotransmission, etc. So over time, I have been building up a series of basic posts about these things, and I try to link to them when I'm writing about more complicated stuff to get you started. So next time I'm going over your head, remember to click the links! They might help you out a lot.

And in the interest of helping you out even more, thus begins GOING BACK TO BASICS week at Neurotic Physiology. I will be reposting my basics about neurotransmission, dopamine, serotonin, depression, and drugs of abuse, to give you a little more idea of where I'm coming from. Please comment with questions, and when I get back I can answer them, or do entire other posts to clarify. And if you have another idea for basics posts that I might cover, please let me know!

And now...back to basics week! Keep checking in, there are a lot of these! And I do my best to be my usual entertaining self.

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