Schizophrenia, Bipolar Disorder Share Common Genetic Cause

Caroline Cassels

January 21, 2009 — The largest family study of schizophrenia and bipolar disorder ever conducted shows that these 2 disorders share a common genetic cause, a finding that challenges the current view that they are separate and distinct conditions.

The analysis, which included more than 9 million individuals from more than 2 million families over a 30-year period, showed that first-degree relatives of individuals with either schizophrenia (35,985 individuals) or bipolar disorder (40,487) had a significantly increased risk for these disorders.

Investigators at the Karolinksa Institutet, in Stockholm, Sweden, found that full siblings were 9 times more likely than the general population to have schizophrenia and 8 times more likely to have bipolar disorder. Maternal half-siblings were 3.6 times more likely to have schizophrenia and 4.5 times more likely to have bipolar disorder than the general population.

This risk was lower for paternal half-siblings, who were 2.7 times more likely to have schizophrenia and 2.4 times more likely to have bipolar disorder.

"Our results were fairly clear-cut and demonstrated that there was a significant increased risk of both schizophrenia and bipolar disorder among first-degree relatives with either of these diseases," study investigator Christina Hultman, PhD, told Medscape Psychiatry. "There was also evidence from the half-siblings and adoptive relatives that this risk is substantially due to genetic factors vs environmental factors, which allows us to conclude that there is a common genetic variation between these 2 psychotic disorders," Dr. Hultman added.

The study is published in the January 17 issue of the Lancet.

Findings Robust

Although traditionally schizophrenia and bipolar disorder have been classified as 2 distinct diseases with different diagnostic criteria and treatment paths, within the past decade results from several molecular genetic studies have suggested that the disorders may share common genes. While these findings were not definitive, Dr. Hultman and her colleagues felt they warranted further investigation.

To examine whether there was a genetic association between the 2 disorders, the investigators linked data from 2 Swedish national registries — a multigenerational national register and a national hospital discharge register, which includes data on all public psychiatric inpatient admissions.

While the investigators suspected there was a common genetic link between the 2 disorders, Dr. Hultman said they were surprised by the magnitude of the shared genetic effect.

Investigators also found that among relatives of individuals with bipolar disorder, there was an increased risk for schizophrenia for all relationships, including adopted children to their biological parents.

Environmental Effects Small but Substantial

Overall heritability for schizophrenia and bipolar disorder was 64% and 59%, respectively. The comorbidity between disorders was 63% and mainly due to additive genetic effects common to both disorders.

Shared environmental effects were small, but substantial — 4.5% for schizophrenia, 4.4% to 7% for bipolar disorder, and 2.3% to 6.2% for both disorders.

According to Dr. Hultman, these results demonstrate that members of families in which someone has either of these affective disorders run an increased risk of developing the same condition and that this is chiefly the result of genetic factors, with only a slight influence of shared environmental factors.

Next research steps include confirmation of these findings and conducting molecular genetic studies in these patients to identify the genes common to both disorders. "If we find these genes and are able to understand their biological function, this could ultimately lead to better treatment," she said.

While it is still too early to make firm clinical recommendations, researchers and physicians should consider this common genetic background when researching and/or treating schizophrenia and bipolar disorder.

Current Classification "Erroneous"

In an accompanying editorial, Michael Owen, PhD, FRCPsych, and Nick Craddick, PhD, FRCPsych, from the University of Cardiff, in the United Kingdom, say the study's findings clearly demonstrate that first-degree relatives of individuals with schizophrenia or bipolar disorder are at increased risk for both disorders and that this is mainly due to genetic factors.

They add that the current classification of these disorders in both the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM) and the World Health Organization's International Classification of Diseases (ICD) as discrete, natural disease entities is erroneous.

"This belief has survived despite the fact that, although typical schizophrenia and bipolar disorder are often seen, many patients have both psychotic and affective symptoms over the course of their illnesses and it is not uncommon for patients to receive both diagnoses at different times," they write.

With efforts well under way to revise the DSM and ICD, Drs. Owen and Craddock conclude that the new diagnostic criteria "encourage the careful measurement and reappraisal of psychopathology. . . . The resulting clinical diagnosis will allow the efficacy of current and future treatments to be monitored in individuals and better serve research into cause, classification, and treatment."

The study was supported by the Swedish Council for Working Life and Social Research and the Swedish Research Council. The authors report no conflicts of interest.