The debilitating mood swings associated with bipolar disorder may be caused in part by disruptions to the balance of calcium and sodium ions in the brain, according to a new report published in Nature Genetics. An international team of scientists conducted the study, the largest to date, which investigated genetic factors that may influence the development of bipolar disorder. Partially funded by the National Institute of Mental Health, the study provides greater insight into the disorder and may indicate new areas of focus for future studies.

Over 4,000 individuals with bipolar disorder took part in the study, along with more than 6,000 control subjects. To search for associations between the disorder and specific genes, the researchers examined a total of 1.8 million genetic variations. Ultimately, they found that individuals with bipolar disorder were much more likely than control subjects to possess variations in two genes that help regulate the flow of ions— Ankyrin 3 (ANK3), which is associated with sodium ions, and CACNA1C, which affects calcium. These genes control the amount of ions present in the brain and the speed at which ions enter and leave brain cells. An imbalance in calcium or sodium ions could affect neuron activity, causing changes in certain brain functions.

Importantly, the researchers point out that ANK3 and CACNA1C are affected by medications commonly used to treat bipolar disorder, including lithium, and both genes may be involved in the origins of the disorder. However, the researchers also stress that multiple factors, both genetic and environmental, could be at play and it’s possible that many individuals have the specific variations in the ANK3 and CACNA1C genes but do not develop bipolar disorder. Still, this study has provided a look at specific genetic mechanisms that may boost an individual’s risk for the disorder. By continuing their work on these genes, the researchers may arrive at new treatments that more effectively aid those whose daily lives are disrupted by unstable moods, energy levels, and behaviors.