Low Levels of Protein in Bipolar Disorder Triggers Epilepsy in Mice

Low Levels of Protein in Bipolar Disorder Triggers Epilepsy in Mice

Researchers have found that low levels of a protein associated with bipolar disorder also triggers epileptic seizures in mice — a discovery that may explain some of the similarities between the two conditions.

The protein, called ANK3, controls the balance between inhibitory and excitatory brain signals. When it’s lacking, it leads to the excessive nerve signaling seen in both epilepsy and bipolar disorder.

Researchers behind the study, “Ankyrin-G isoform imbalance and interneuronopathy link epilepsy and bipolar disorder,” hope the insights will lead to research for better treatments for both epilepsy and bipolar disorder. The work was published in the journal Molecular Psychiatry.

“We became very interested in a gene called ankyrin 3, or ANK3, a decade ago when we discovered it coded for a partner of two other genes that are mutated in some people with epilepsy,” Dr. Edward C. Cooper, associate professor of neurology, molecular and human genetics, and neuroscience at Baylor College of Medicine in Texas, said in a press release.

Large genetic studies in patients with bipolar disorder revealed that ANK3 was also connected to the psychiatric condition.

“Although there are important differences, we noted similarities between bipolar disorder and epilepsy: both cycle, both are risk factors for the other, and both are currently treated using many of the same drugs,” Cooper said.

But although researchers noticed the similarities, they could not explain them. The ANK3 gene can give rise to several alternative proteins, and researchers didn’t know what the variant linked to bipolar disorder did in the brain.

To better understand these connections, the research team started studying a mouse model of bipolar disorder. The team discovered that brain cells that sent inhibitory signals — decreasing the output of other cells — contained a different version of the protein than excitatory neurons, which increase the output of their target cells.

The version of the protein that is low in bipolar patients was selectively lost from the inhibitory neurons, making them lose their normal signaling patterns. Since excitatory nerve cells were unaffected, the result was an excessive activating signaling.

Mice that lacked the “inhibitory” version of ANK3 did not only develop behavior similar to that seen in bipolar patients, they also had severe seizures and an increased risk of sudden death.

“This showed us that imbalance in ANK3 function can result not only in excessive circuit sensitivity and output leading to bipolar disorder, but also severe epilepsy,” Cooper said.

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Magdalena is a writer with a passion for bridging the gap between the people performing research, and those who want or need to understand it. She writes about medical science and drug discovery. She holds an MS in Pharmaceutical Bioscience and a PhD — spanning the fields of psychiatry, immunology, and neuropharmacology — from Karolinska Institutet in Sweden.


  1. Monica Hetle says:

    I got the diagnose epilepsy when I was 23 years old. My brother startet to find his diagnose at the same age. He now has the diagnose bipolar. I had an surgery at the left Hippocampus. But I also had attacs at the right Hippocampus. Hippocampus is at the top of Amygdala under Hyphotalamus. We have an very unstabile background. A lot of stress. I have an stephdad which is an alcholic, my brothers dad. And I did not meet my biological dad before I was 35 years old. Our mother is an very unstabile whoman. I was with an psycologist to speak about my background. He told me to keep my mother on an long distance and agreed very much that I moved when I was very young. She also mistreated me very hard and almost killed me when I was newly surgeried. I have studied a lot about Psycopatic and I mean that it is the way she behaves. She`s got an very unstabile background. Her mother got nine children but she did not take care of them. My mother and here familie is very unstabile. They do not accepte the throuth and tries to stop that it is beeing told. With other words, a lot of stress. That is what I belive is the reason why we both have become ill. I have studied that psycopati, shizhofreni and bipolar is at the same area in the brain. But that bipolar is possible to treat? I have tried 20 epileptic medications. I had a lot of sideeffects and ended 6 times in coma because I had to stop the medication. Now, I use 300 mg Vimpat and 900 mg Orfiril Long. But still I can get some small attacs which lasts for 2 minutes. I don`t have any relation with my mother anymore. My brother has a relation both to his father and his mother. It is very difficult to get him away from them. I don`t know. Do you agree a bit with my theories? That we both have become ill because of all the stress?

    • Magdalena Kegel says:

      Dear Monica,
      Thank you for sharing your story. I am really sorry to hear about the circumstances that you grew up in. Stress is a known trigger of psychiatric disease, including bipolar disorder, but while there are studies showing that stress can make seizures more frequent in patients with epilepsy, I am not aware of studies that indicate that stress can cause the condition. That said, it is impossible to exclude the possibility that a stressful family situation may have contributed to the condition in your case.

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