Researchers in Germany say they have discovered the molecular root cause of the euphoric phases that occur in bipolar disorder.
Researchers used an analysis of patient data, as well as experiments with mice, to show how the NCAN gene results in the manic symptoms of bipolar disorder.
Those with bipolar disorder are on an emotional roller coaster. During the down phases, they suffer from depression, diminished drive and often from suicidal thoughts. The manic episodes are characterized by restlessness, euphoria and delusions of grandeur.
While researchers knew that the NCAN gene plays a major part in how manias manifest, the “functional connection” was not clear, according to Dr. Markus M. Nöthen, director of the Institute of Human Genetics at the University of Bonn.
In the new study, researchers evaluated the genetic data and the related descriptions of symptoms from 1,218 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 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 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, she said.
A team working with Dr. Andreas Zimmer, director of the Institute of Molecular Psychiatry at the University of Bonn, then examined the molecular causes created by the NCAN gene. To do this, the researchers studied mice in which the gene had been “knocked out.”
“It was shown that these animals had no depressive component in their behaviors, only manic ones,” said Zimmer.
These mice were considerably more active than the control group and showed a higher level of risk-taking behavior, according to the researchers. In addition, they tended to exhibit increased reward-seeking behavior, which manifested itself by their unrestrained drinking from a sugar solution offered by the researchers.
Finally, the researchers gave the manic mice lithium, which is a standard therapy for humans.
“The lithium dosage completely stopped the animals’ hyperactive behavior,” said Zimmer.
The researchers said the responses of humans and mice regarding the NCAN gene were practically identical.
“We were quite surprised to see how closely the findings for mice and the patients correlated,” said Nöthen. “This level of significance is very rare.”
The scientists want to perform further studies of the molecular connections of the disorder, with a view towards new therapies.
“This is a great prerequisite for advancing the development of new drugs for mania therapy,” said Rietschel.
The results were published in The American Journal of Psychiatry.
Source: University of Bonn