Depression - A Chemical Imbalance or Something More?

For a little over three decades, we have been given information suggesting that depression is caused by a “chemical imbalance” in the brain – namely an imbalance of the brain chemical serotonin.

The serotonin theory of depression was first proposed in the 1960s and started to be widely promoted by the pharmaceutical industry in the 1990s with its efforts to market a new range of antidepressants, known as SSRIs or selective serotonin-reuptake inhibitors. The idea was endorsed by official institutions like the American Psychiatric Association, which to this day tells the public that “differences in certain chemicals in the brain may contribute to symptoms of depression”.

Countless doctors all over the world have repeated this message in their private surgeries and in the media. People accepted what they were told, and many started taking antidepressants with the belief that they had something wrong with their brain which needed an antidepressant to put it right. In the period of this marketing push, antidepressant use climbed, and they are now prescribed to one in six of the adult population in America, for example.

Some leading psychiatrists have suggested that there is no satisfactory evidence to support the idea that depression is a result of abnormally low or inactive serotonin. Others continue to endorse the theory. Until now, there has been no comprehensive review of the research on serotonin and depression that could enable firm conclusions either way.

The fact that SSRI antidepressants act on the serotonin system appears to support the serotonin theory of depression. SSRIs temporarily increase the availability of serotonin in the brain, but this does not prove that depression is caused by the opposite of this effect.

There are other explanations for antidepressants’ effects. In fact, drug trials show that antidepressants are barely distinguishable from a placebo (dummy pill) when it comes to treating depression. Also, antidepressants appear to have a generalised emotion-numbing effect which may influence people’s moods, although we do not know how this effect is produced or much about it.

Based on the research of the University College of London when they compared levels of serotonin and its breakdown products in the blood or brain fluid. Overall, this research did not show a difference between people with depression and those without depression.

Another area of research has focused on serotonin receptors, which are proteins on the ends of the nerves that serotonin links up with and which transmit or inhibit serotonin’s effects. Research on the most investigated serotonin receptor suggested either no difference between people with depression and people without depression or pointed to the fact that serotonin activity was actually increased in people with depression – the opposite of the serotonin theory’s prediction.

Research done on the serotonin “transporter”, which is the protein that helps to terminate the effect of serotonin (this is the protein that SSRIs act on), suggested that, if anything, there was increased serotonin activity in people with depression. These findings can be explained by the fact that many participants in these studies had used or were currently using antidepressants.

The University College of London has looked at research that explored whether depression could be induced in volunteers by artificially lowering levels of serotonin. Two systematic reviews from 2006 and 2007 and a sample of the ten most recent studies (at the time the current research was conducted) found that lowering serotonin did not produce depression in hundreds of healthy volunteers.

Very large studies involving tens of thousands of patients have looked at gene variation, including the gene that has the instructions for making the serotonin transporter. They found no difference in the frequency of this gene between people with depression and healthy controls.

Some studies that have included people who were taking or had previously taken antidepressants show evidence that antidepressants may actually lower the concentration or activity of serotonin. Though the serotonin theory of depression has been one of the most extensively researched biological theories on the origins of depression. But this recent study by the University College of London shows that this view is not supported by scientific evidence and calls into question the basis for the use of antidepressants.

It is not clear whether antidepressants exert their effects as placebos, or by numbing emotions, making it unclear whether or not they do more good than harm.