Schizophrenia, Bipolar Disorder: Gene Link?

Jan. 15, 2009 -- The largest study ever to track bipolar disorder and schizophrenia within families offers evidence that the two psychiatric disorders share a common genetic cause.

For more than a century the psychiatric community has debated whether schizophrenia and bipolar disorder were two distinct disorders or were more connected.

Over the course of their illnesses, many patients experience similarities in certain symptoms characteristic of both, such as manic mood swings in bipolar disorder and psychosis in schizophrenia.

Recent genetic studies suggest a common genetic cause for the two conditions. But earlier studies in families have not supported this conclusion, finding no increase in bipolar disorder in family members of schizophrenics and vice versa.

Family Links: Bipolar Disorder, Schizophrenia

In an effort to help settle the question, researchers in Sweden linked a comprehensive national health registry to equally comprehensive hospital discharge records.

Three decades of registry and hospital data (1973 to 2004) involving 9 million Swedes from 2 million families were analyzed to determine risk for schizophrenia and bipolar disorder among biological and nonbiological relatives of patients with one or both of the disorders.

Close to 36,000 people with schizophrenia and 40,500 people with a diagnosis of bipolar disorder were identified.

The analysis revealed that:

• First-degree relatives (parents, siblings, or offspring) of people with either schizophrenia or bipolar disorder were at increased risk for both of these conditions. 
• If a sibling had schizophrenia, full siblings were nine times more likely than the general population to have schizophrenia and four times more likely to have bipolar disorder. 
• If a sibling had bipolar disorder, they were eight times more likely to have bipolar disorder and four times more likely to have schizophrenia. 
• Half siblings who shared the same mother were 3.6 times more likely to have schizophrenia if their half sibling had schizophrenia and 4.5 times more likely to have bipolar disorder if their half sibling had bipolar disorder. Half siblings who shared the same father had a 2.7-fold increase in schizophrenia risk and a 2.4-fold increase in bipolar disorder. 
• Adopted children with a biological parent with one of the disorders had a significant increase in risk for the other.

Shared and non-shared environmental factors also contributed to risk, but they were less important influences than genetics.

The findings appear in the Jan. 17 issue of the journal The Lancet.

'Time to Rethink Disorders'

"It is time that we rethink the way we view these disorders," study co-author Christina Hultman, PhD, tells WebMD. "And it is clear that we need more genetic studies to help us better understand this shared risk."

In an editorial accompanying the study, Cardiff University dean of medicine Michael Owen, MD, PhD, suggested that the earlier family studies were far too small to show the genetic link between schizophrenia and bipolar disorder.

In an interview with WebMD, Owen called the latest research very strong, with major implications for how patients are managed.

"When someone receives a diagnosis of schizophrenia it is easy for clinicians to overlook mood disorder and other symptoms that don't fit with that diagnosis," he says. "The same is true for psychotic symptoms that may occur in people labeled with a diagnosis of bipolar disorder."

He adds that it is important for clinicians to recognize that symptoms can, and often do, change over time.

"Most patients don't fit neatly into categories, and the more questions you ask the more likely you are to find a combination of psychotic and mood symptoms," he says.

John H. Krystal, MD, of Yale University Medical Center and the VA Connecticut Healthcare System, agrees.

He tells WebMD that psychiatry has long struggled with "a gray zone" of patients who do not neatly fit into the categories of bipolar disorder and schizophrenia.

He adds that the new research could have major implications for the development of new treatments for the psychiatric disorders.