Could We Finally Understand Bipolar Disorder and Come Up with a Permanent Fix?

June 12, 2018 – Researchers at the RIKEN Center for Brain Science in Japan have found a link between mitochondrial dysfunction and bipolar disorder. In mouse studies, they identified the gene, SLC25A4, responsible for creating the protein ANT1 (adenine nucleotide translocase type 1) which impacts mitochondrial function producing the chemical energy that feeds cells. When the gene is defective a chemical imbalance occurs and one of the side effects of that imbalance impacts serotonin, a neurotransmitter that is known to impact behaviour in those affected. Bipolar disorder is associated with an imbalance of serotonin in the brain and current treatment tries to address this through a number of drugs. The Japanese researchers have published their findings in the June 11, 2018 issue of Molecular Psychiatry. The finding of the link between the defective gene, the metabolic signaling system, and mitochondrial dysfunction had never previously been identified.

Mitochondria have a special place in the evolution of eukaryotic life on Earth. The Endosymbiont theory of how this all began states that a long time ago a primitive pre-eukaryotic cell ingested another type of cell.  That pre-eukaryotic cell tried to digest the second one we call a mitochondrion. But instead of digesting it the mitochondrion stayed intact and alive with its exceptional abilities soon incorporated into the ingesting cell’s structure. Today no mitochondrion exist anywhere on Earth outside a eukaryotic cell. Every animal, plant, and fungi, all eukaryotes, have descended from that moment in time when the synergistic partnership was formed.

Mitochondrion serves an important cellular function. It metabolizes carbohydrates and fatty acids and converts them to a chemical called adenosine triphosphate (ATP). Eukaryotes use that chemical to drive metabolism. So one can imagine any defective gene that influence mitochondrion activity could have a significant impact on the behaviour of the host.

What the Japanese scientists discovered was ANT1 mutation and its association with bipolar disorder in mice. Mice with the mutated gene had enhanced serotonergic activity leading to behavioural highs and lows as levels of serotonin changed. This impacted neurons in an area of the brain also affected by Parkinson’s Disease. The researchers didn’t directly link the ANT1 mutation to bipolar disorder. But they did conclude it was associated with elevated risk of developing the condition.

So what does this mean for those afflicted with bipolar disorder?

This brain disease begins between the teens and twenties in humans. It is ranked among the top 10 causes of disability globally according to the World Health Organization, affecting 60 million. It is characterized by mood swings from mania to depression. Effective treatment includes medications that maintain brain chemistry balance, as well as psychological and psychiatric treatment. About 60% of those suffering from the disorder can function normally with treatment but the balance of 40% don’t.

This new discovery has profound implications for future treatment of the disorder. Rather than serotonin-targeting drugs, the underlying mitochondrial dysfunction which affects signaling within the brain could be repaired with gene therapy leading to an effective cure.