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Scientists launch major study into depression

JUNE 05, 2008

Scientists have launched a groundbreaking £1.1M study into the causes of clinical depression.Depression will affect up to 25% of the population at some point in their lives. It also has been shown to have a strong genetic component. For example, if one of your close family members has depression, your chance of also being a sufferer is three to four times the general population risk.

Now University of Aberdeen researchers have joined forces with the University of Liverpool and the Institute of Psychiatry, King’s College London to try to find the genetic causes of depression.They believe the answers could lie with short DNA sequences which act as ‘genetic switches’ controlling key genes in an area of the brain that influences mood. These switches ensure that certain genes are only used in the correct parts of the brain at the proper times and in the right dose. Any changes in these can cause imbalances in the amount of critical proteins in the brain that may increase susceptibility to depression.Unlike genes, little is known of these switches, technically known as enhancers, because up until now they have been very hard to find.

Recently, however, it was found that these switches were so important in evolution that they have been kept, nearly unchanged, through hundreds of millions of years from a time before the dinosaurs. Dr Alasdair MacKenzie, Senior Lecturer at the University of Aberdeen, and the scientist leading the study, explained:  “Only by comparing the genomes of species as diverse as mice, marsupials and birds has it been possible to identify these switches as, in many cases, they are located far away from the genes they control. The distances involved are as surprising as having a light bulb in London with the switch for controlling it in Liverpool.”Comparing the genomes of different species has helped them to identify the switches responsible for controlling genes known to be involved in depression, as well as addiction, obesity and inflammatory pain.

This new study funded by the Medical Research Council will allow them to build on their earlier work and also analyse common sequence differences found in the general population which can result in increased risk of developing depression. Researchers in Aberdeen and Liverpool will study the functional effect of these ‘switch’ sequences. Scientists at the Institute of Psychiatry at King’s, led by Dr Gerome Breen and Professor Peter McGuffin, will look at common variations found in these sequences using DNA samples taken from thousands of patients with chronic depression.

It is hoped the three year study – which will also examine why some sufferers do not respond to anti-depressant treatments – will ultimately pave the way for new drugs to treat the condition.Dr Alasdair MacKenzie,said: “This study would have been impossible even four years ago. It is only through advances in the sequencing of the DNA of many different species that we can now use powerful computers to pick out the most important bits of the human genome that includes the switches needed to control genes.“In addition to depression, this technology has the potential for exploring the causes of a number of other disorders including chronic pain, obesity or even cancer.”

Professor Quinn at the University of Liverpool said: “This study hopes to discover how the same genes in different people are controlled in slightly different ways in the parts of the brain that control fear and mood.“We hope to link differences in the switches that control these genes with susceptibility to distressing conditions such as depression and chronic anxiety. Also, we hope to find out how these differences may change the way that depressed patients respond to their medicines.”

Dr Breen, jointly leading the Institute of Psychiatry at King’s involvement, said: “We can now analyse millions of genetic variations in the human genome but it is only studies like that that will allows usto track down those that are important in disorders such as depression.” Professor McGuffin added: “We are delighted to be part of such a potentially exciting project and look forward to our collaboration further enlightening clinical research and practice.”
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