Anti-depressants work in many ways

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Groundbreaking new research seems to show that what was previously only considered one of the side-effects of drugs used to treat depression may actually also be responsible for their main therapeutic mood-lifting benefit.

Many of the anti-depressants prescribed to patients block re-uptake, the process by which chemicals in the brain (called neurotransmitters) are absorbed back into a transmitting neuron (brain cell) after they have been released into the synapse.

However, a seven-year study carried out by a team of German researchers found that these drugs also reduce the concentration of protein-like ceramides in the brain.

"In reality, it seems that this effect actually plays a central role in lifting mood," said Johannes Kornhuber, from the psychiatry department at Erlangen's University Clinic.

Too much ceramide

In the study published by Erich Gulbins and others in the June issue of Nature Medicine, mice were genetically modified to produce increased ceramide levels. The scientists discovered that too much ceramide in the brain leads to depression-like behaviour.

When the ceramide levels were reduced, new neurons were able to form, and depression-like behaviour diminished. If the research is confirmed, the researchers will have discovered a new cause of the illness.

"We think that in cases of depression there is too much ceramide present," said professor Kornhuber. Stress could also prevent the formation of neurons.

Until now, it was thought that the most important cause of depression was reduced signal transmission at the contact points between neurons, explained Kornhuber.

The mood-lifting effect of many anti-depressant medications was ascribed to the blocking of the re-uptake process, which increases the concentration of the neurotransmitters at the contact points.

"But neurotransmitters work quickly, so improvement should be noticeable within a couple of hours," explained Kornhuber.

In practice, anti-depressants only begin to work after several weeks. "That in itself was an indicator that there were other mechanisms at work."

Human trials are the next step after the successful therapeutic study with mice.

Very confident

"We are very confident," said Kornhuber.

New drugs can now be produced with the purpose of reducing ceramide levels. However, it will take several years before any new anti-depressant drug gets regulatory approval and is made available to the people suffering from depression.

"This is first-class work," said Professor Florian Holsboer from the Max Planck Institute for Psychiatry in Munich.

"We have experienced many disappointing results when attempting to replicate results from experiments with mice in human trials, but I hope that it is successful this time."

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