Decrypting manic depression

Although many people have heard of bipolar disorder, most people don't actually know much about this complex, psychiatric disease. Much about bipolar disorder, in fact, remains to be researched and understood.

But now, a recent study has shed new light on the genetic factors behind the disorder. The study confirms the implication of three genes previously suspected of contributing to bipolar disorder and breaks new ground by identifying two additional genetic regions likely to be associated with the disorder.

Complex and serious illness

Bipolar disorder involves "pathological changes and swings in mood ranging from severe, energized states of mania to the incapacitating and diminished, low-energy states of depression," said Melvin McInnis, a psychiatrist and professor at the University of Michigan and principal investigator at the Prechter Bipolar Research Fund.

But expression of bipolar disorder, also known as manic depression, can vary greatly. Bipolar I involves severe mood episodes, while bipolar II presents more mild, "hypomanic" states. The length of mood cycles can also vary greatly from person to person.

Even people who have a single manic episode can be characterized as bipolar, said Markus Nöthen, head of the Institute of Human Genetics at the University of Bonn Biomedical Center and one of the three authors of the study. Yet someone "can also have rapid cycling episodes, with many episodes of depression and mania," Nöthen explained. About 1 percent of the population suffers from it, he added.

During a manic phase, a bipolar person has a "charged sense of energy, thinking - their emotions can run the gamut," McInnis told DW. In a manic phase, a person "can rock from feeling very high to very irritable and angry," he said.

The depressive phase is often so severe that a bipolar person can be consumed by thoughts of suicide. About 20 percent of individuals with manic depression end up committing suicide, McInnis explained.

These mood swings of course severely affect a bipolar person's life - bipolar disorder "can disrupt relationships, it can derail career ambitions," McInnis said. "It's a very fascinating, complex, and potentially very devastating illness."

Narrowing down genetic factors

That manifestations of the illness can vary so greatly likely has to do with the large amount of possible causes for bipolar disorder. Bipolar is "a typical multifactor disorder," Nöthen told DW, meaning that genetic as well as environmental factors contribute to the disease. Genes contribute 60 to 70 percent in development of the disease, he explained.

Then, there's no simple cut-and-dried bipolar gene. "Our current understanding is that there are many genes with relatively small effects contributing to the disorder," Nöthen said.

In their study, published March 11 in "Nature Communications," Nöthen and others confirmed that three previously identified genes or "loci" are likely to play a role in bipolar disorder. "The replication of previously identified loci or risk factors is very important - science really thrives on replication of existing findings," McInnis noted.

But that the study implicated two new genes is also "of considerable interest," McInnis said. "It puts some new players on the field."

Nöthen described the large sample size as providing the "power" behind his study, which looked at the frequency of genetic markers in 9,700 bipolar patients and 14,200 control subjects. It's among the largest sample sizes for such a study to date, said McInnis, who was not affiliated with the study.

Drafting manic depression's architecture

The actual biological mechanism behind bipolar disorder is still not completely understood, although it's likely related to impaired transmission of signals between neurons, as well as imbalances of neurotransmitters in the brain. One gene implicated in the current study "plays an important role in the transduction of the signal into the cell," Nöthen said.

While most medications currently used to treat manic depression address the symptoms, Nöthen said he hopes his research can eventually contribute to development of medication that addresses the underlying cause.

Nöthen stressed that scientists are still in the beginning stages of understanding the genetic components of bipolar disorder, while McInnis compared such work to that of the anatomist: "We're identifying critical landmarks in the anatomy of the genome as it relates to bipolar disorder."

McInnis said he was encouraged by the study's findings, "This is a very critical step in a long journey."