Online Courses and CE: We offer a series of online educational programs for professionals and the public. Visit us here for previews and discounts on our online programs.

Follow PsychologySalon on Facebook: Become a fan of the PsychologySalon page; updates will appear in your news feed.

Looking for a therapist? We have eleven registered psychologists in our clinic, and we are accepting new clients. For information, visit

Friday, 4 November 2011

Medications: What is the Monamine Hypothesis?

(This is part of a series of posts on the basics of psychopharmacology that I’m posting so that I can refer people back to it.  Here's the first of the series on neurons, and here's one on signal transmission from neuron to neuron.  )

Monoamines are neurotransmitters that, naturally, have a single (mono) amino group as part of their chemical structure. When it comes to brain-based neurotransmitters, there are several monoamines:

Serotonin, or 5-HT
Epinephrine (or adrenaline)
Norepinephrine (or noradrenaline)

When neurons release a monoamine into the gap between neurons, the chemical crosses and binds to the receptor sites on the next neuron, potentially resulting in the next neuron firing. A naturally-occurring substance called monoamine oxidase (MAO) sits in this gap, however, and begins breaking down some of the neurotransmitter before it can cross.

In the 1950s it was discovered that MAO inhibitors, which prevent the action of MAO, were effective in reducing clinical depression. By reducing the action of MAO, more neurotransmitter might be able to cross the gap and bind to the next neurons.

This was exciting. The results suggested that the problem in depression might be a deficiency in one or more of the monoamines. Here’s the reasoning: If there isn’t enough, say, serotonin available, then less will be released into the gap. MAO will then break it down and not enough will get to the next neuron in line. Stopping MAO means that the small amount of serotonin is able to stay in the gap long enough to trigger the next neuron.

Subsequent studies suggested that certain drugs which affected mainly serotonin (5-HT) and norepinephrine systems also worked against depression. These drugs came to be known as the tricyclic antidepressants, and included imipramine and amitriptyline. They operate by reducing reuptake – the process whereby the sending neuron gathers back some of the transmitter before it crosses to the next cell.

The result of these two lines of evidence was the monoamine hypothesis, which (in a nutshell) states that depression is caused by a deficiency of serotonin and/or norepinephrine, and can be corrected by medications which enable these deficient amounts of serotonin to last long enough in the gap between neurons to pass the signal along.

What is a good hypothesis?

Hypotheses are particularly useful if they meet two primary criteria:

1. They point the way toward useful action.
2. They generate testable questions.

Note that a hypothesis doesn’t have to be true to be good.  “The moon is made of green cheese” is a reasonably good hypothesis, because we can build a spacecraft, visit the moon, collect a sample, and see if it really is green cheese.

The statement “Depression is caused by an imbalance in undiscovered and unmeasurable energy fields”, for example, fails both tests. It’s unclear what to do about these imbalances, and the lack of measurability makes it hard to test the idea. The very fact that we can’t detect the fields or anomalies in question makes the hypothesis useless – the product of imagination rather than observation.

So is the monoamine hypothesis a good one?

The monoamine hypothesis, by contrast to the ideas above, is admirable. It generates a number of ideas that can be tested.  For example:

  • Depressed individuals should, on average, show differences in serotonin levels or function relative to nondepressed individuals.
  • People should generally have lower levels of serotonin or serotonin function when they are depressed than when they are not depressed.
  • Medications that correct these differences should correct the depression to at least some extent, compared to measures (like placebo treatments) that work primarily by belief and expectancy.
  • If we take nondepressed volunteers and take measures to produce these differences associated with depression (like feeding them a diet that will produce a serotonin deficiency), we should see an upswing in depressive symptoms.
  • Measures, such as drugs, that produce opposite effects on serotonin function should have opposite (or at least different) effects on mood.

We can quibble with any of these hypotheses and find possible exceptions to them, but on the whole they are reasonably sound. If we go out and test them and find support for none of these ideas, then we can reasonably say that the monoamine hypothesis has not been supported and is probably best tossed on the junkheap of scientific history.

You can guess, I think, where this is going eventually.

No comments:

Post a Comment