If low serotonin levels aren't responsible for depression, what is?
September 30th,2010 by Ann
We've all seen the commercials. There's a sad little white marshmallow, a person in a darkened room unable to attend the party, or unable to enjoy a beautiful day. And then a voice shouts out that here is hope. That depression of yours is a result of imbalances in chemicals in your brain and, if you can correct those chemicals, you will feel better. Easy!
It's not that these commercials sell you a pack of lies. Most antidepressants do increase the levels of chemical messengers in the brain called neurotransmitters. A specific type of neurotransmitter, the monoamines, appear to be the chemicals of choice for these drugs. Scientists once thought that simply increasing the amount of monoamines in the brain would treat the symptoms of depression. And that meant, of course, that depression itself must be caused by low levels of monoamines, particularly serotonin.
For years, scientists have tried to find drugs that increase these serotonin levels in the brain safely, and tried to find evidence that decreases in monoamines are responsible for depression itself.
Well, after much searching, we did find a lot of very interesting things. But some things just didn't add up.
The first problem was one of time. If low serotonin levels were really what made you feel depressed, then increasing levels of serotonin should alleviate the symptoms right away. But antidepressants don't work immediately, and in fact can take more than a month to alleviate symptoms. Strike one.
The second problem was one of whether the drugs actually worked. Serotonin-specific antidepressant drugs don't work on everyone. In fact, new estimates show that the current antidepressants on the market only work in about 60% of patients. If low serotonin levels were really responsible for depression, then increasing serotonin should have worked on more than 60% of patients. Strike two.
The final problem is one of evidence. If low serotonin levels were responsible for depressed mood, then we should be able to induce depression in people by decreasing serotonin, and we should find low levels of serotonin in patients with depression. But neither of those things exist. Decreasing serotonin in humans can lower your mood, but it doesn't always work. And studies looking for low serotonin in depressed patients have been inconclusive. It appears that even though antidepressants increase serotonin, a lack of serotonin doesn't cause depression (kind of like aspirin treats a headache, but headaches are not caused by a lack of aspirin). Strike three. Serotonin is out.
So what's in? After all, antidepressants do work in some patients. It's instructive to look at other things these drugs are doing in the brain.
Antidepressants increase levels of neurotransmitters in the brain, but they also increase neurogenesis, the birth of new cells in the brain. Throughout your life, you will grow new neurons in an area of the brain called the hippocampus. And if you take antidepressants for several weeks, you will get increased neurogenesis.
These new neurons correspond to changes in animal behaviours that are associated with long-term antidepressant treatment. The behaviours are novelty-induced hypophagia, which measures how much of a tasty food an animal will eat in a novel environment and reflects aspects of anxiety and anhedonia (the inability to experience pleasure); and the tail suspension test, which measures behavioural despair.
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