P&S Journal: Winter 1995, Vol.15, No.1
New Evidence for Genetic Cause of Manic Depression
P&S researchers at the New York State Psychiatric Institute have found evidence that a region on chromosome 21 contains a gene for manic depression, also known as bipolar disorder.
Dr. Miron Baron, professor of clinical psychiatry, and his colleagues reported their findings in the November 1994 issue of Nature Genetics.
The study involved more than 900 people from 47 families with a high concentration of bipolar disorder-38 families from the United States and nine from Israel. One U.S. family of 67 individuals included 18 members who had diagnoses ranging from bipolar disorder to recurrent major depression to cyclothymia. The researchers found that DNA markers from region q22.3 of chromosome 21 gave evidence of linkage to the disorder in this family and, possibly, in other families.
The search for a predisposing gene for bipolar disorder has been frustrating; findings from earlier promising studies could not be confirmed. Lessons drawn from those studies and applied in this study, namely the study of a large, carefully diagnosed population, the analysis of multiple DNA markers, and the robustness of the results to changes in diagnostic and statistical parameters, give a measure of confidence in the reported linkage to chromosome 21q22.3. But, as Dr. Baron points out, "given the uncertainties in studying complex disorders and the checkered course of linkage results in psychiatric genetics, caution is advised in interpreting our finding." Replication by independent laboratories is necessary. If linkage is confirmed, steps will be taken to identify and characterize the putative disease gene, which could lead to a test to determine those at risk and, more importantly, suggest new therapies when the genetic mechanism is understood.
Many genetic diseases, such as cystic fibrosis and Huntington's chorea, are more straightforward. They are inherited through known mechanisms that can be tracked in families. Other diseases, such as diabetes, Alzheimer's disease, and bipolar disorder, are more complex; they likely involve multigene systems and environmental factors and display a variable and complicated clinical picture. Recent successes in locating genes for diabetes and Alzheimer's disease, however, offer hope for advances in other complex disorders, including mental illness.
The study was part of a large scale search for bipolar disorder genes. Dr. Baron and his colleagues plan to enlarge their study population to more than 2,000 individuals in nearly 90 extended families. Hundreds of DNA markers spanning the human genome will be tested with the aim of detecting all genes of moderate to large effect in this illness. In the study reported in November, the researchers studied between 5 and 153 markers per family. In the family with the strongest evidence for linkage, 78 DNA markers were studied, including 21 on chromosome 21, the one suspected of harboring the implicated gene.