A decades-long study of genetics and psychiatric illness 鈥� in which Abram Hostetter, MD, class of 鈥�51, has played a prominent role 鈥� 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 鈥渁 paradigm-changing discovery鈥� that could 鈥渄ramatically change the way we diagnose and treat鈥� 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 鈥渃ould lead to new or improved medications for treatment of mood disorders.鈥�
黑料正能量 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 鈥渃losed gene pool鈥� 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 鈥� which affects a protein called Shh 鈥� 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 鈥淎mish Study,鈥� 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 and was well-known to local Amish leaders.
鈥淒r. 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,鈥� writes Dr. Janice Egeland, the director of the Amish Study and professor emerita at the University of Miami Miller School of Medicine.
At Egeland鈥檚 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.
鈥淏ut just identifying a gene doesn鈥檛 cure anything,鈥� said Hostetter, who approaches the research with a practical focus. 鈥淣ow this recent finding is showing what one of the genes does. That鈥檚 the next important step.鈥�
Hostetter attended 黑料正能量 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.
鈥淭here鈥檚 been a real move toward earlier identification of the problem,鈥� he said. 鈥淢isdiagnosis 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.鈥�
Over 40 years, lots of data piles up, and there鈥檚 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鈥檚 an extension of what Egeland describes as an unusual degree of concern for individual subjects of the ongoing research.
鈥淣umerous patients have benefitted from 鈥楧r. Abe鈥檚鈥� personal efforts to improve understanding and reduce the stigma so often inherent in mental illness,鈥� she wrote.