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Biological Evidence of Bipolar Disorder – Part 2: Genetics
Bipolar blogger Natasha Tracy explores the state of genetic research into bipolar disorder.
Part one of this series discussed the biological differences between a brain with bipolar disorder and one without and while several differences were noted, none can definitively be used to diagnose bipolar disorder.
Unfortunately, it’s a similar story with the genetics of bipolar disorder. While twin, family ,and adoption studies have been conducted within the bipolar population—and we know that a person with a first-degree relative (like a mother or father) with bipolar disorder is about seven times more likely to develop the disease—we still can’t pinpoint the genetics.
Genetics and Bipolar Disorder
It was hoped that like with Huntington’s disease—an illness that also manifests psychiatric symptoms—we would be able to find a gene that causes bipolar disorder, but unfortunately, a genetic study has produced the likelihood that possibly hundreds of genes may be linked to bipolar disorder. It is likely that many genes increase the risk of bipolar disorder, but it’s only in specific combinations that the disease actually manifests.
Genes Linked to Bipolar Disorder
Naturally, the discussion of genes is necessarily very complicated and studies do differ in their analysis of which genes contribute to bipolar disorder. Based on thousands of samples, here is what scientists are currently thinking:
- Two genes linked to voltage-gated calcium channels (ANK3 or ankyrin G) and CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel)) have been linked to bipolar disorder. This makes sense as calcium channel blockers have been used to treat bipolar disorder and lithium, the most effective treatment for bipolar disorder, is known to down-regulate these mechanisms in mice brains. Anticonvulsants may also have calcium channel blocking effects.
- ANK3 and CACNA1C have also been linked to schizophrenia, so as with neurobiological markers, genes point to a common underpinning for both bipolar disorder and schizophrenia.
- Both the CLOCK (circadian locomotor output cycles kaput) and ARNTL (aryl hydrocarbon receptor nuclear translocator-like) genes are linked to the circadian rhythm and bipolar disorder, and in the case of the CLOCK gene, mutating it in mice produces a mania-type state that is treatable with lithium.
- A low-functioning serotonin transporter gene (HTTLPR) has also been associated with bipolar disorder. This gene is one of the targets of select serotonin reuptake inhibitor (SSRI) medication.
Clinical Implications of Genes in Bipolar Disorder
While this and other genetic work is ongoing, none of these genes have a sizable enough effect, on their own, to warrant genetic testing for bipolar disorder.
However, these genes are not only leading us towards objective diagnosis, they are also leading us towards a better understanding of how bipolar medication works and who will likely respond to specific medications or medication types. Lithium has already been better understood thanks to genetic testing as has other medication and genes may also be able to predict who is more likely to suffer from antidepressant-induced mania.
important to remember that the bulk of this understanding has happened only in
the last five years. The next five years may take us to places we haven’t even
Please see here for more on genetics and bipolar disorder.
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