A decades-long study of genetics and psychiatric illness – in which Abram Hostetter, MD, class of ’51, has played a prominent role – continues to yield new clues about the causes of bipolar disorder and guide the search for new treatments. In October 2014, a research team published findings that people with a rare form of genetic dwarfism, known as Ellis-van Creveld Syndrome (EvC), are protected from developing bipolar disorder. The findings, derived from the study of an Old Order Amish community in Lancaster County, Pennsylvania, are “a paradigm-changing discovery” that could “dramatically change the way we diagnose and treat” bipolar and other affective disorders, said lead author Dr. Edward Ginns of the University of Massachusetts Medical School, in a press release.
Hostetter, who was not a co-author on the recent paper, called the results exciting because they “could lead to new or improved medications for treatment of mood disorders.”
About 30,000 members of the Old Order Amish community in Lancaster County trace their descent exclusively from 32 people who immigrated from modern-day Germany to Pennsylvania in the 1750s. Genetically distinct from other Amish communities in the country, this “closed gene pool” presents a unique opportunity to study the genetic components of mental illness. In some families within this group, both bipolar disorder and EvC are more prevalent than in the general population.
According to the recent study, statistical analysis of these two conditions within the study group shows that a person with the genetic mutation that causes EvC is prevented from developing bipolar disorder. Linking that genetic mutation – which affects a protein called Shh – directly to bipolar and other affective disorders represents a breakthrough in understanding the genetic basis of these conditions.
Hostetter has been involved with the project, known in the field as the “Amish Study,” since it began in 1976. When he was invited to participate, Hostetter was working in private psychiatry practice in Hershey, Pennsylvania, where he regularly saw Old Order Amish patients. Hostetter had a further connection to that community because his grandfather had been a moderator of Lancaster Mennonite Conference and was well-known to local Amish leaders.
“Dr. Hostetter brought to the Amish Study his special expertise based on a life-long exposure to the cultural setting and religious traditions of the Old Order Amish, as well as his experience as a practicing psychiatrist and hospital medical director involving Amish-Mennonite patients,” writes Dr. Janice Egeland, the director of the Amish Study and professor emerita at the University of Miami Miller School of Medicine.
At Egeland’s invitation, Hostetter joined a group of psychiatrists that established specific criteria for diagnosing bipolar disorder in members of the Amish study group. They eventually identified more than 100 patients with the disorder. In 1987, Egeland, Hostetter and six others published the first research connecting bipolar disorder to a specific gene, in a paper that has since been cited hundreds of times.
“But just identifying a gene doesn’t cure anything,” said Hostetter, who approaches the research with a practical focus. “Now this recent finding is showing what one of the genes does. That’s the next important step.”
Hostetter attended EMU for two years before transferring to the pre-med program at Goshen College, another Mennonite college in Indiana. After graduating in 1953, he went to Jefferson Medical School in Philadelphia, Pennsylvania. While collaborating with Egeland and other colleagues on the Amish Study, he continued in private practice in Pennsylvania until retiring in 2003. He now lives in Charlottesville, Virginia, but remains involved with the Amish Study as it approaches its 40th year.
In addition to linking bipolar disorder to a specific human gene, Hostetter and his colleagues have also used their research to identify childhood risk factors that suggest an eventual bipolar diagnosis.
“There’s been a real move toward earlier identification of the problem,” he said. “Misdiagnosis is one of the big problems in dealing with this illness, and this study has been recognized as having led the way in greater accuracy and specificity of psychiatric diagnoses.”
Over 40 years, lots of data piles up, and there’s always new insight to tease out. Another paper Hostetter says he and his colleagues might try to tackle would demonstrate inheritance of specific sub-types of bipolar disorder that variously manifest with symptoms like violence, grandiosity, hypersexuality and others. This spring, he plans to pay clinical visits to some of the families that have participated in the study. It’s an extension of what Egeland describes as an unusual degree of concern for individual subjects of the ongoing research.
“Numerous patients have benefitted from ‘Dr. Abe’s’ personal efforts to improve understanding and reduce the stigma so often inherent in mental illness,” she wrote.