August 17, 2008
Two Bipolar Depression Genes Found

Here's another report on our role as puppets with genes as the puppeteers. A group of researchers has published a paper in Nature Genetics offering evidence that genes involved in calcium ion flow across nerve membranes might contribute to bipolar depression.

The largest genetic analysis of its kind to date for bipolar disorder has implicated machinery involved in the balance of sodium and calcium in brain cells. Researchers supported in part by the National Institute of Mental Health, part of the National Institutes of Health, found an association between the disorder and variation in two genes that make components of channels that manage the flow of the elements into and out of cells, including neurons.

"A neuron's excitability whether it will fire hinges on this delicate equilibrium," explained Pamela Sklar, M.D., Ph.D., of Massachusetts General Hospital (MGH) and the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, who led the research. "Finding statistically robust associations linked to two proteins that may be involved in regulating such ion channels and that are also thought to be targets of drugs used to clinically to treat bipolar disorder is astonishing."

People with bipolar disorder have my sympathy. Until researchers can come up with better treatments for it a lot of people have to go thru a lot of suffering. Nature is a sadistic bastard.

Since researchers think many genes contribute to bipolar it is hard to pick out the genes that contribute from all the background noise. But the genes they suspect are involved in key functions done by neurons and the researchers had a large sample of bipolar and non-bipolar study participants for which they did DNA tests.

To boost their odds, Sklar and colleagues pooled data from the latter two previously published and one new study of their own. They also added additional samples from the STEP-BD study and Scottish and Irish families, and controls from the NIMH Genetics Repository. After examining about 1.8 million sites of genetic variation in 10,596 people including 4,387 with bipolar disorder the researchers found the two genes showing the strongest association among 14 disorder-associated chromosomal regions.

Variation in a gene called Ankyrin 3 (ANK3) showed the strongest association with bipolar disorder. The ANK3 protein is strategically located in the first part of neuronal extensions called axons and is part of the cellular machinery that decides whether a neuron will fire. Co-authors of the paper had shown last year in mouse brain that lithium, the most common medication for preventing bipolar disorder episodes, reduces expression of ANK3.

Variation in a calcium channel gene found in the brain showed the second strongest association with bipolar disorder. This CACNA1C protein similarly regulates the influx and outflow of calcium and is the site of interaction for a hypertension medication that has also been used in the treatment of bipolar disorder.

The fact that a hypertension medication works against bipolar is interesting though not unprecedented. Lots of drugs are originally developed for one reason and found to have benefits for other disorders.

Note that they looked at 1.8 million sites of known genetic variation. Ongoing projects aimed at identifying all sites where we genetically differ make this sort of study possible where it wouldn't have been possible even 5 years ago. Faster and cheaper ways to do DNA testing are going to cause a massive torrent of brain gene discoveries over the next 5 years.

Share |      Randall Parker, 2008 August 17 07:31 PM  Brain Genetics

Lively said at August 24, 2008 1:58 PM:

Hello, I found your site very helpful thank you for sharing your insights. Fisrt, my husband has been diagnost several times with different docs, stating that he's adhd, general anxieties and possible bipolar two. however, should he be taken Lamictal 100mg and the meds for general anxities?

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