In the late 1990s the Department of Psychiatry at Johns Hopkins University placed an advertisement in a number of newspapers, including this one, recruiting Jewish research subjects. The ad read: “Ashkenazi Jewish families are needed to help scientists understand the biological basis for schizophrenia and bipolar disorder.” Now a new study recruiting schizophrenia patients in northern New Jersey is seeking volunteers. Although that study is recruiting from the Jewish community as well as the general population (see related story), past studies have targeted Jewish populations, in particular Ashkenazi Jews. Has this occurred because Jews are more likely to suffer from mental illness than other groups? Scientific research has not supported this notion; experts estimate the incidence of schizophrenia in the Ashkenazi Jewish population to be no higher than that of the general population (about one percent).
Why would scientists be so interested in studying mental illness in Jewish groups? Schizophrenia is a complex mental disorder that is thought to occur as a result of the interaction of multiple genetic factors and environmental factors. One way the genetic contribution has been analyzed is by using twin studies, which reveal that identical twins – who share all their genes – have significantly higher concordance for schizophrenia (i.e., where both have the disease) than do fraternal twins (who share about 50 percent of their genes). That outcome supports the idea that schizophrenia has a significant genetic basis.
On its Website, the Johns Hopkins program explained its justification for using Jewish populations. “Due to a long history of marriage within the faith, which extends back thousands of years, the Jewish community has emerged from a limited number of ancestors and has a similar genetic makeup. This allows researchers to more easily perform genetic studies and locate disease-causing genes.” (See www.hopkinsmedicine.org/epigen/ashkenazim.htm.) Thus, disease genes may be easier to identify in a more homogeneous genetic population. Ashkenazi Jews have served as a very convenient and generally willing group for research studies. In addition, since it is a fairly homogeneous group, the Ashkenazi population is useful for studies on other aspects of schizophrenia, such as response to, and efficacy of, psychiatric drugs.
It is important to remember that schizophrenia is not determined only by genetic factors. Environmental factors can play an important role in triggering the disease. They can include obstetric complications, infections, substance abuse, and social adversity. Schizophrenia is also hard to study since its diagnosis is often complex. There is no single symptom or disease-specific marker that permits clear diagnosis. There is also considerable variability in the mode and extent that schizophrenia is expressed in patients.
Dr. Ann Pulver, of Johns Hopkins Medical Center, has conducted research on the genetics of schizophrenia over many years and has published numerous papers pertaining to the genetic factors involved in the disease. Every person inherits tens of thousands of genes from his or her parents and those genes contain chemical instructions for development and physical makeup, determining an individual’s functioning, health, and predisposition to disease. The instructions, encoded in DNA, are located on the 23 pairs of chromosomes – the microscopic genetic packages found in every cell of the body.
Pulver’s group and other scientific collaborators have identified some genetic markers that are associated with mental disease. For instance, they discovered that on chromosomes 1, 3, 6, 8, 11, 12, and 18 there are sites that may be associated with bipolar (manic-depressive) disorder. Pulver’s research also showed that chromosomes 10 and 22 harbor candidates for schizophrenia-susceptibility genes that may increase a person’s chance of developing the disease.
The brain is an incredibly complex organ, hence it is no surprise that the genetic underpinnings of schizophrenia appear to be complex, and that researchers have not identified a single specific gene that causes the disease. In order to analyze the data from the many scientists working on this problem, a centralized Website (www.schizophreniaforum.org) was developed to catalogue the numerous studies and try to make sense of conflicting data. The goal of the Website is to serve as a central repository for data on the genetics of schizophrenia, provide the opportunity to determine which studies are consistent with one another, and reconcile studies that have conflicting results.
In more than 1,400 studies, scientists have reported on an astounding 761 genes that may be associated with a predisposition to schizophrenia. The Website lists the top 29 genes and reports which studies found a link between a gene and the disease and which studies found no link. Some of the genes listed include: DISC1 (“disrupted in schizophrenia” 1), located on chromosome 1; GABRB2 (a gene for a brain protein that binds neurotransmitters) on chromosome 5; and DRD2 (a dopamine receptor gene) on chromosome 11.
One example of conflicting research results pertains to the COMT gene, which produces an important brain enzyme. Studies by Israeli researchers at Hebrew University, together with scientists at the pharmaceutical company IDgene, suggested that a variant of the COMT gene, located on chromosome 22, was linked to schizophrenia in Ashkenazi Jews. But a group of British researchers failed to find this link in the two groups they studied: Ashkenazi Jews and Irish subjects. Thus the significance of COMT in development of schizophrenia is still unresolved.
A 2008 study published by collaborating scientists from Israel, England, China, Ireland, and the United States suggested RELN, the reelin gene, as a new candidate for a schizophrenia gene. The study showed that a variant of reelin, a gene known to have a role in brain development, is associated with higher incidence of schizophrenia in females. It is not clear why there would be a link between this gene and schizophrenia in women but not in men. The authors acknowledge that “despite the relatively large heritability of schizophrenia, efforts to identify the molecular risk factor have so far yielded equivocal results.”
Pulver reports that these types of studies are critical to gain better understanding of the disease and to find more effective treatments. She pointed out one flaw in past research projects that should be addressed and remedied: “The majority of people coming into our study are men,” she said. “Men are over-represented in our studies; it’s 3 to 1, men to women.”
“This has great implications for females in clinical studies,” explained Pulver, who encourages women to participate in clinical trials. Many studies of drugs, for instance, can reveal which drug had the fewest negative consequences and the best responses. Those studies are mainly based on male subjects. “But men and women are different,” said Pulver. “We need to identify more Ashkenazi Jewish women with schizophrenia. These studies are the highest priority right now.”
Yeshiva University Prof. Rabbi Moshe Tendler, a medical ethicist, has taken a dim view of studies that focus only on Ashkenazi Jews. He has stated that genetic studies will reawaken the idea that “Jews carry genes that are polluting the world. That’s the basis of eugenics. If you have a ‘disease’ gene, don’t you owe it to society not to propagate that gene?”
The use of Jewish subjects in many genetic research studies may have added to anti-Semitic notions concerning mental illness in Jews, and some of those heinous ideas are expressed on anti-Jewish sites on the Web. For instance, a writer on Mid-East Realities (www.middleeast.org) claims that Dr. Arnold Hutschnecker (Richard Nixon’s longtime psychiatrist) believed that Jews are “carriers of schizophrenia” and display paranoia, aggressiveness, and racism.
Although concerns have been voiced about research studies leading to the stigmatizing of Jews, clearly there are tremendous benefits reaped from studies that are carefully designed and carried out. When scientists have access to research subjects and are able to scientifically test new drugs and other treatments, there are potential benefits to participants as well as to society as a whole. The underlying causes of schizophrenia will be understood only after careful study, data collection, analysis, and scrutiny in many different populations of affected individuals, including Jews.