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Bipolar disorder: Can it be inherited?

by Tami Port MS

Bipolar disorder results from a combination of factors; the interplay of genetics and environmental stressors. How much of a role does heredity have in the development of this mental illness?

Early research on the genetics of bipolar disorder relied on twin studies and examination of inheritance patterns among family members. Now that the human genome has been decoded, science is getting closer to identifying all of the specific genes involved in the development of this mood disorder.

* Inheritance Patterns of Bipolar Disorder *

Family studies of inheritance patterns, as well as twin and adoption studies of those with bipolar disorder have revealed that first-degree relatives of affected individuals have a higher risk of developing bipolar symptoms. Still, a child of a bipolar and a nonbipolar parent have less than a 15% chance of developing the disorder, although those odds may increase if there are others in the family who have a mood disorder.

Studies of identical twins have shown that if one twin is bipolar, the other has at least an 85% chance of developing the disorder. Twins certainly share many of the same environmental factors as well, both in utero and throughout childhood, but shared experience does not account for the extremely high likelihood that genetically predisposed twins will share the disorder.

So it is established that bipolar disorder tends to run in families. But now, with the human genome mapped, scientists are starting to pinpoint the actual genes that are linked to the disorder.

* Genetics of Bipolar Disorder *

Within the last few years, researchers have identified several genes that appear to be associated with the disorder. Because a number of genes are involved in development of bipolar illness, the inheritance patterns are not straightforward, as indicated by the fact that children of a bipolar parent have a relatively small risk of developing the disorder. All those who may have a genetic predisposition don't necessarily ever end up developing bipolar symptoms.

The involvement of several genes, suggests that a range of biochemical problems can occur in people who possess a genetic predisposition for bipolar disorder, and that perhaps, the specific type and number of genetic abnormalities contribute to how the disorder manifests in an individual.

Our understanding of genetic disorders has exploded since the completion of Human Genome Project (HGP) in 2003. This 13-year project was launched cooperatively by the U.S. Department of Energy and the National Institutes of Health and participated in by researchers from all over the world.

The Human Genome Project:

* identified all of the genes in the of human DNA
* determined the sequences of the 3 billion chemical base pairs that make up the genetic code
* stored this information in databases
* developed data analysis tools and technologies so that the information could be used to learn more about genetic disorders

Completion of the Human Genome Project now enables scientists to learn more about genetic disorders by comparing the genome (all the DNA) of individuals that have a certain disease with the human genetic code deciphered by the Genome Project. If there are, for example, consistent abnormalities certain segments of DNA of those with bipolar disorder, it would suggest that those are areas of DNA that may be involved with development of the disorder.

Research that has taken place since the human genome was decoded, has revealed that:

* Two different variations of a gene called Ankyrin 3 (ANK3), on chromosome 10, each pose independent genetic risk factors for bipolar disorder.

* Variation in a gene, CACNA1C, on chromosome 12, also appears to be involved in bipolar disorder,

* Abnormalities in the GABA-A receptor genes, scattered over several chromosomes, seem to be present both in those with bipolar disorder and also in people with schizophrenia. GABA receptors are a type of neurological receptor that responds to the neurotransmitter gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter of the central nervous system.

* Molecular genetic studies have also found information on chromosomes 12, 14, and 15 that relates to the age of onset for bipolar disorder.

* Our Future Understanding of Bipolar Disorder *

With the huge expansion of knowledge in the area of molecular genetics, we may soon be able to understand exactly what causes bipolar disorder, how the disorder differs between individuals and why there are variations in the age of onset. And this is not just an academic pursuit. Knowing exactly what is contributing to a persons' bipolar experience may allow for very specific use of pharmaceuticals and other treatments that could effectively treat those with bipolar disorder on an individual basis.

* Sources *

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Anonymous. Bipolar Disorder Genetics; Studies from National Institute of Mental Health in the area of bipolar disorder genetics published. Genomics & Genetics Weekly; May 8, 2009, p.114.

Craddock N; Sklar P. Genetics of bipolar disorder: successful start to a long journey.
Trends Genet; Feb. 2009 Vol.25, Iss.2; p.99-105.

Healthy Place, Genetics of Bipolar Disorder.

Potash JB; Bienvenu OJ. Neuropsychiatric disorders: Shared genetics of bipolar disorder and schizophrenia. Nat Rev Neurol; June 2009, Vol.5, Iss.6; p.299-300

Nick Craddock; M. C. O'donovan; M. J. Owen,; Psychosis Genetics: Modeling the Relationship Between Schizophrenia, Bipolar Disorder, and Mixed (or "Schizoaffective") Psychoses. Schizophrenia Bulletin; May 2009. Vol.35, Iss.3; p.482.

Smoller JW, Finn CT. Family, twin, and adoption studies of bipolar disorder. Am J Med Genet C Semin Med Genet; Nov 2003 15; 1 23C(1): 48-58.

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