Researchers discover role of gene in bipolar disorder

Re­searchers from the University of Bonn and the Central Institute of Mental Health in Mannheim have discovered the role of NCAN gene in the manic symptoms of bipolar disorder. The latest issue of The American Journal of Psychiatry has published the results of the large scale study, based on patient data and animal models, reports Science Daily journal. People with bipolar disorder are on an emotional roller coaster. During depressive phases, they suffer from depression, diminished drive and often, also from suicidal thoughts. The manic episodes, however, are characterized by restlessness, euphoria, and delusions of grandeur. The genesis of this disease probably has both hereditary components as well as psychosocial environmental factors. The NCAN gene plays a major part in how manias manifest. University of Bonn’s Institute of Human Genetics Director Prof. Dr. Markus M. Nothen, said, “It has been known that the NCAN gene plays an essential part in bipolar disorder. But until now, the functional connection has not been clear.” In a large-scale study, researchers evaluated the genetic data and the related descriptions of symptoms from 1218 patients with differing ratios between the manic and depressive components of bipolar disorder. Using the patients’ detailed clinical data, the researchers tested statis­tically which of the symptoms are especially closely related to the NCAN gene. “Here it became obvious that the NCAN gene is very closely and quite specifically correlated with the manic symptoms,” said Prof. Dr. Marcella Rietschel from the Central Institute of Mental Health in Mann­heim. According to the data the gene is, however, not responsible for the depressive episodes in bipolar disorder. A team working with Prof. Dr. Andreas Zimmer, Director of the Institute of Molecular Psychiatry at the University of Bonn, examined the mole­cular causes effected by the NCAN gene. The researchers studied mice in which the gene had been ‘knocked out’. “It was shown that these animals had no depressive component in their behaviours, only manic ones,” said Prof. Zimmer. These knockout mice were, e.g., considerably more active than the control group and showed a higher level of risk-taking behaviour. In addition, they tended to exhibit increased reward-seeking behaviour, which manifested itself by their unrestrained drinking from a sugar solution offered by the researchers. The researchers then gave the manic knockout mice lithium – a stan­dard therapy for humans. “The lithium dosage completely stopped the animals’ hyperactive behaviour,” said Prof. Zimmer. The results also matched for lithium; the responses of humans and mice regarding the NCAN gene were practically identical. It has been known from prior studies that knocking out the NCAN gene results in a developmental disorder in the brain due to the fact that the production of the neurocan protein is stopped. “As a consequence of this molecular defect, the individuals affected apparently develop manic symptoms later,” said Prof. Zimmer. “We were quite surprised to see how closely the findings for mice and the patients correlated,” said Prof. Nothen. “This level of significance is very rare.” The scientists plan further studies on the molecular connections of this disorder with a view towards developing new therapies.