With no single gene a root cause, bipolar disorder appears to be the collaboration of five or so regions of the human genome, including a newly discovered gene associated with an enzyme helping to conduct signals into the body’s nerve cells.

"There is no one gene that has a significant effect on the development of bipolar disorder," Markus M. Nöthen, director of the Institute of Human Genetics of the University of Bonn Hospital, said in a statement. "Many different genes are evidently involved and these genes work together with environmental factors in a complex way."

In searching for the origin of bipolar disorder, Nöthen and his colleagues last year recorded 2.3 million genetic regions within materials from participants recruited from the study, including healthy people serving as a control. Biostatistical analysis then revealed five genetic regions associated with a higher risk of developing the disorder, including the newly discovered “ADCY2” gene on chromosome five as well as the “MIR2113-POU3F2” region on chromosome six.

Though the other three regions had previously been described by science, the analysis further strengthened the association. "These gene regions were, however, statistically better confirmed in our current investigation,” Nöthen said. “The connection with bipolar disorder has now become even clearer.”

Most interesting to the researchers, however, was the enzymatic activity of ADCY2. "This fits very well with observations that the signal transfer in certain regions of the brain is impaired in patients with bipolar disorder," Nöthen said. "Only when we know the biological foundations of this disease can be also identify starting points for new therapies.”

Known also as bipolar affective disorder, the illness is characterized by periods of mania — elevated or agitated mood — alternating with severe bouts of depression. As many as one to three percent of people around the world may suffer from the disorder, striking men and women equally across racial and ethnic lines. Today’s treatments for the often debilitating illness involve psychotherapy and mood-stabilizing medication, such as lithium and benzodiazepines — with no cure in sight.

Though many people with bipolar disorder effectively manage the condition, patients often suffer a volatile emotional life with sudden shifts in mood, and manic periods bringing delusions of grandeur, increased motivation, and a decreased need for sleep. Joyful heights of creativity are followed by crashes into the leviathan of despair.

In this investigation, Nöthen and colleagues in Mannheim and in Bonn analyzed genetic data from more than 2,2000 patients with bipolar disorder and another 5,000 health recruits for comparison. Co-investigator Marcella Rietschel, of the Central Institute of Mental Health, likened the study to looking for a needle in a haystack, but says a breakthrough would occur with a big enough sampling size. "The investigation of the genetic foundations of bipolar disorder on this scale is unique worldwide to date," she said.