Genetic Causes of Bipolar Disorder
As genetic influences are thought to play a part in bipolar disorder (BPD), when a person is assessed for this condition she is asked whether anyone in her family has, or had, this or any other psychiatric problems.
Family Linkage Studies
Many health problems arise from two different influences--genetic and environmental --and maybe a combination of these, that is, someone may have a "predisposing" genetic factor that is only brought out when there is an environmental factor present, such as stress. As reviewed by Nick Craddock and Pamela Sklar in "Trends in Genetics" February, 2009 edition, for the general population the risk of having BPD is around 1 percent, however for those with one affected relative (parent or sibling) the risk is 5 to 10 percent, and for identical twins it is 40 to 70 percent. There is also a wider risk of other psychiatric disorders occurring in relatives of people with BPD, especially schizophrenia. These statistics suggest that there is indeed a genetic part to BPD, but that it is not the only factor.
Some people with one or more distinct genes are almost definitely going to have a problem linked to that gene, for instance people with the gene for Huntington's disease. The same cannot be said for BPD, that is, there is no one gene that means a person will have this condition.
Specific Genes Linked to Bipolar Disorder
Studies that analyze data from a number of different experiments, such as those by Dr. Matthew McQueen found in the October, 2005 edition of the "American Journal of Human Genetics" and Dr Ricardo Segurado in the July, 2003 edition of the same journal, have found a wide variety of genes in separate studies that seem to be linked to BPD, many of which can be found expressed in the brain. However, only a few of these are significantly different in people with BPD compared to non-affected people over a number of different studies.
Prof Paul Lichtenstein et al, carried out a family study and found a linkage between BPD and schizophrenia, as published in the January 17, 2009 edition of "The Lancet." This is reflected by the finding of, among other groups, Dr. Colin Hodgkinson et al, reported in the November, 2008 "American Journal of Human Genetics" that the gene DISC1 (disrupted in schizophrenia 1), which codes for a protein involved in signaling pathways linked to neurodevelopment and cytoskeleton function, is similarly altered in these two disorders.
That decreased levels of DISC1 may be a factor in BPD has been shown by a mouse model created by Dr. Jean Marx, reported in the November 16, 2007 edition of "Science," where the expression of DISC1 is deliberately reduced. This produced behavior akin to depression and psychosis, and as this behavior responded positively to medications used in BPD it suggests that DISC1 plays at least some role in the pathogenesis of BPD.
Other genes that have been shown disrupted in BPD studies include two genes associated with neuronal function, diacylglycerol kinase (DGKH), found by Dr. Amber Baum et al and published in the February, 2008 edition of "Molecular Psychiatry," and ankyrin 3 (ANK3), found by Dr. Manuel Ferreira et al, as published in the September, 2008 edition of "Nature Genetics," and neuregulin 1 (NRG1), as shown by Dr. Pippa Thomson et al in the January, 2007 edition of "Molecular Psychiatry," which is involved in neuronal development, function, and survival and is also linked to schizophrenia.
Evidence in both family and DNA analysis studies show that there are genetic factors associated with BPD. As means to identify genetic contribution to diseases become more sophisticated, researchers will be able to more accurately pinpoint predisposing factors.
References
- "Human Mutation;" Searching Genetic Risk Factors for Schizophrenia and Bipolar Disorder: Learn from the Past and Back to the Future; Maaike Alaers M and Jurgen Del-Favero; August 2009
- "Current Opinion in Genetics & Development;" Genetic Causality in Schizophrenia and Bipolar Disorder: Out with the Old and in with the New; David Porteous; June 2008
- "Trends in Genetics;" Genetics of Bipolar Disorder: Successful Start to a Long Journey; Nick Craddock and Pamela Sklar; February 2009
