Discovery of Bipolar Disorder Gene Shifts Understanding of Environmental Factors

Researchers have discovered two new gene regions connected to bipolar disorder.

The disorder is a type of mental illness which is characterised by episodes of elevated or agitated mood, known as mania, which often alternates with episodes of depression.

Scientists from Bonn, Mannheim and Basel, who worked with an international collaboration of researchers, discovered two new gene regions that are connected to the prevalent disease. Three additional, previously known gene regions were confirmed.

Sven Cichon, professor for human genetics at the University of Basel, said the search for genes involved in the manic-depressive disorder is extremely difficult. He explained: "The search for genes involved in the manic-depressive disorder is like looking for a needle in a haystack. The contributions of individual genes are so minor that they normally cannot be identified in the 'background noise' of genetic differences.

He added: "Only when the DNA from very large numbers of patients with bipolar disorder are compared to the genetic material from an equally large number of healthy persons can differences be confirmed statistically."

As of yet, the causes of the disease are not yet fully understood. It is believed psychosocial triggers may contribute to the illness, as well as genetic factors. Cichon added: "There is no one gene that has a significant effect on the development of bipolar disorder. Many different genes are evidently involved and these genes work together with environmental factors in a complex way."

Known environmental causes include the upbringing of patients. It is estimated that a person who has one parent with bipolar disorder has a 15 to 20% chance of having the condition.

Using automated analysis methods, researchers recorded about 2.3 million different regions in the genetic material of patients and comparators. The subsequent evaluation using biostatistical methods revealed a total of five risk regions on the DNA associated with bipolar disorder.

In recent years, scientists have already successfully decoded several genes associated with bipolar disorder. New genetic data from 2,266 patients with manic-depressive disorder and 5,028 control persons were obtained, merged with existing data sets and analysed together. In total, data on the genetic material of 9,747 patients were compared with data from 14,278 healthy persons.

The gene ADCY2 on chromosome five and the so-called MIR2113-POU3F2 region on chromosome six were the two new gene regions identified. The risk regions ANK3, ODZ4 and TRANK1 have already been described in prior studies.

Professor Marcella Rietschel, from the Central Institute of Mental Health of Mannheim, said: "These gene regions were, however, statistically better confirmed in our current."

Researchers are paying particular attention to the gene region ADCY2 and the part it plays in bipolar disorder. It codes an enzyme which is involved in the conduction of signals into nerve cells.

Professor Markus Nöthen from Bonn, explained the connection further: "This fits very well with observations that the signal transfer in certain regions of the brain is impaired in patients with bipolar disorder."

The result of the research, he added, it to clarify the cause of the illness and pinpoint new therapies. The research was published in Nature Communications.

Around 1% of the population suffers from bipolar disorder throughout the course of their lives. Patients shift between emotions, such as manic phases with delusions of grandeur and increased drive, during which they may feel they do not require sleep. Those with bipolar disorder will also experience episodes of deep depression, in which they may have suicidal thoughts.