UK And Japanese Researchers Find Link Between The Serotonin Transporter Gene And Bipolar Affective Disorder

October 26, 1997

Manic depression, more properly called bipolar affective disorder (BPAD), is a form of depression that affects about 1 in 200 people, and is characterised by alternating phases of euphoria and sadness. BPAD runs in families, and the reason for this is that most, but not all, of its causes are inherited.

Bipolar affective disorder is a complex genetic disorder -- this means that there are likely to be a number of different genes involved in each person affected, as well as causes related to personal experiences such as significant life events. However in some families, bipolar affective disorder might be caused by a single gene.

Intensive effort is currently being put into identifying the genes involved. The reason for this effort is to help to understand the underlying causes of BPAD, so that both preventative and therapeutic treatment can be improved. Most of the genes involved are likely to be common in the population and not necessarily defective. Rather, it is likely that a person experiencing the symptoms of bipolar affective disorder may have a certain mixture of genes which leads to unstable moods. Each gene may also have beneficial effects and is likely to be carried by many people who do not experience the illness. Having such a "susceptibility" gene will increase a person's chance of developing bipolar affective disorder, by perhaps two or three-fold or more.

One candidate gene which might cause BPAD codes for the serotonin transporter. This protein is a molecular hoover -- which sucks up excess serotonin in the brain after it has finished acting on neurons. Serotonin is involved in a variety of behaviours, including sleep, activity, feeding and moods, all of which are affected in manic depression.

The serotonin transporter is also the main site of action of a variety of drugs used to treat clinical depression, such as fluoxetine (Prozac). The illicit drug MDMA (ecstasy) also acts on the serotonin transporter by releasing serotonin into the brain, causing a period of elation followed by depressive feelings as the drug wears off, an experience which has parallels to BPAD.

Recently, a research group in the UK lead by Dr David Collier, Professor Robert Kerwin and Professor Robin Murray at the Institute of Psychiatry, London, examined the serotonin transporter gene for a role in bipolar affective disorder. They used a genetic marker within the serotonin transporter gene to test if there were differences in the gene between people with BPAD and those without.

It was found that one variant of the gene was more common in people with bipolar affective disorder, indicating that it is a possible genetic cause of the illness. However, as for other areas of scientific investigation, it is important that other workers are able to find the same differences between their volunteer patients and controls.

Other scientists have examined the same gene, and two recent large studies, one from the Department of Psychological Medicine, University of Wales College of Medicine, and one from the Department of Psychiatry, Teikyo University in Tokyo, Japan, have confirmed this initial finding. Although some studies using fewer patients have not reported the same findings, overall there is a growing weight of evidence that inherited variation in the serotonin transporter gene is a cause of BPAD. It is possible to speculate that variations in the gene might cause instability in the regulation of the amount of serotonin in the brain.

The serotonin transporter represents the first gene identified as a probable cause of bipolar affective disorder, and it is hoped that it will lead to a greater understanding of the causes of the disease and result in improvements in treatment. However, additional work will be required to determine exactly why the gene causes BPAD, since this is presently unknown. For example, the serotonin system and the serotonin transporter itself are responsive to stress and hormones, and it may be possible to determine how these factors affect regulation of the gene and lead to the development of illness. It may also be possible to use information about the serotonin transporter in order to improve treatments using antidepressant drugs, and even to tailor treatment to individual patients, depending on which inherited type of the gene they have. For information on these three Molecular Psychiatry articles, please contact the authors:

This article is from the October-November issue of Molecular Psychiatry, an independent peer-reviewed journal published by Stockton Press/Macmillan Press.

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For information on the scientific aspects of the article please contact the authors. Pre-prints of the articles can be obtained from Ms. Julie Vianello: phone: +1 301 496-6979; FAX: +1 301 402-1561; e-mail:

Molecular Psychiatry

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