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Genetics of Bipolar Disorder

Susanne Bengesser and Eva Reininghaus

The high hereditary factor of Bipolar Disorder has been proven by many twin-, adoption- and family-studies already decades ago. Concordance rates between monozygotic twins are even as high as 40-70%. Children of two affected parents have a lifetime-risk of 50-65% to fall ill with Bipolar Disorder, while children with one affected parent show a risk of 25% to get Bipolar Disorder. Therefore psychiatric genetics is highly important to detect the genetic blueprint of Bipolar Disorder to invent prevention strategies, as well as individualized pharmacotherapy and new medication targets. Interestingly top susceptibility genes belong to the ion channel group, growth hormones, clock genes, neurotransmitter systems, Lithium sensitive pathway and other important groups. A detailed and exciting description is given by the authors within this book. Furthermore basic principles of genetics, gene-environment-interactions and genetic overlaps between psychiatric diseases are described to picture the whole painting of Genetics of Bipolar Disorder.


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Bipolar disorder is a highly heritable disease with a polygenetic mode of inheritance. Although molecular psychiatry is still in its infancy, a huge amount of possible susceptibility genes have been discovered, but still with inconsistent results. Top susceptibility genes belong to channelopathies and ion channel associated pro- teins; especially ANK3 and CACNA1C are important susceptibility genes. A gene coding for the brain derived neurotrophic factor, BDNF, seems to be asso- ciated with bipolar disorder in Caucasians, but not in Asians. It could be a labor- atory marker for bipolar disorder, because serum levels are decreased in patients with bipolar disorder. Another promising predisposing gene group includes the “clock genes”, among which are ARNTL, CRY1, CRY2 and PER1-3. Although the serotonergic system might be expected to play a major role, because the neurotransmitter imbalance theory has dominated the pathogenesis of affective disorders for decades, serotonin receptor genes are not very likely to influence bipolar disorder to a major degree. The very well examined serotonin transporter polymorphisms are more likely to be involved in pathogenesis of manic- depressive disease. Other neurotransmitter systems, such as the dopamine and noradrenaline systems do not show overwhelming results either. The genes of the GABA and glutamate systems show some positive results. Beside those well- examined gene groups numerous newly detected possible susceptibility genes exist. A detailed description of all candidate genes and their polymorphisms is given within this book.The detection of all these susceptibility genes has great impact on future nosology and therapy. Boundaries between bipolar...

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