June 8, 2008 It is important to identify the endophenotypes -- traits associated with a clinical disorder -- that can serve as a roadmap for detecting disease-related genes. That is why Deborah L. Levy, Ph.D., associate professor of psychology in the Department of Psychiatry at Harvard Medical School and director of the Psychology Research Laboratory at McLean Hospital, is studying families to detect relatives who are carriers of the genes for schizophrenia and bipolar disorder, even though these individuals don’t have the diseases themselves.
"One of the key issues in any genetic study is to distinguish individuals who are gene carriers from individuals who are not gene carriers," explained Dr. Levy. In single gene disorders, such as cystic fibrosis and Huntington's disease, 25 percent and 50 percent of family members, respectively, have the same illness. In contrast, only 6.5 percent of family members of people with schizophrenia actually have the illness, which means most relatives don’t have symptoms of the illness but may still be gene carriers.
To find the relatives who are likely carriers of genes for schizophrenia and bipolar disorder, Dr. Levy and her colleagues have zeroed in on four discernable schizophrenia-related traits that occur in well family members at a much higher rate than schizophrenia itself: difficulty following a slow moving target with one’s eyes, syntax errors or idiosyncratic use of language, subtle anomalies involving the midline of the face , and difficulty filtering out noises and other irrelevant stimuli (a condition known as sensory gating).
These traits, according to Dr. Levy, are much more common in families with schizophrenia. For example, idiosyncratic use of language (a trait similar to the thought disorder observed in schizophrenia) occurs in 37 percent of clinically unaffected first-degree relatives of individuals with schizophrenia, a rate that is almost six times higher than schizophrenia in the same families. When the rates for thought disorder and schizophrenia and related clinical conditions are combined, the proportion of potential gene-carrying relatives is close to 50 percent, consistent with a dominant gene, and much higher than the 6.5 percent rate of schizophrenia in the same families.
“With diseases like schizophrenia and bipolar disorder, identifying the genes is just the starting point,” noted Dr. Levy. “The ultimate goal is to discover the biological processes these genes initiate in the brain, ultimately leading to better treatments in the future.”
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