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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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6. Conclusion


Bipolar disorder is a highly heritable disease, which has been proven by many family, twin and adoption studies, as well as modern genetic approaches. A long list of possible susceptibility genes has been discovered so far (see page 21). Interestingly top candidates belong to the Ion channel group and Ion channel associated proteins- especially ANK3 and CACNA1C are favorite predisposing genes. CACNA1C codes for the alpha1C subunit of the L-type voltage-gated calcium channel and influences verbal fluency aside from other important func- tions. ANK3 codes for an adaptor protein, which regulates the assembly of vol- tage-gated sodium channels at axon initial segments. Until now both genes show genome wide significant evidence of association with bipolar disorder. Another promising chapter of bipolar disorder research is the growth hormone group. BDNF seems to be associated with bipolar disorder in Caucasians, but not in Asians. BDNF could even be a laboratory marker for bipolar disorder because serum levels are decreased in manic, depressed and euthymic states of manic- depressive disease. BDNF is responsible for neuronal development, synapse formation, serotonergic axon growth, memory acquisition and consolidation, and antidepressant effect, therefore a role in pathogenesis of bipolar disorder is not unlikely. A further candidate gene group includes the “clock genes”, including ARNTL, CRY1 and 2, PER1-3. Changes in circadian rhythms are typical fea- tures in mood disorders. This goes along with the positive study results for many “clock gene” polymorphisms in smaller association studies, but not in recent GWAS. Although everybody would expect the serotonin...

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