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 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.

Hostetter, an alumnus of two Mennonite colleges, is part of a University of Miami team that has been researching mental illness among generations of Amish families in Lancaster County since 1976.

He and project leader Janice Egeland, professor of psychiatry, behavioral sciences, epidemiology and public health at the University of Miami, worked for years together out of an office in Hershey, Pa. They assembled a team of about a dozen others to assist them.

“The Old Order Amish of Lancaster County have a lower incidence of mental illness than the general population, but a much higher incidence of bipolar disorder, “ said Hostetter.

Bipolar disorder, also called manic depression, often leads to suicide. “It’s in the blood,” said an Amish grandmother—or siss im blut, in Pennsylvania German—when Egeland began her research.

Bipolar disorder is characterized by episodes of mania or depression that typically recur and often become more frequent and severe during a lifetime. It’s estimated that about 1 percent of the U.S. population has a major mood disorder.

Over the years, scientists discovered an association between mood disorders and two known genetic markers. In other words, people suffering from bipolar disorder have inherited it from their parents.

Hostetter and Egeland found that Old Order Amish families are ideal subjects for genetic studies for a number of reasons:

• They descend from a limited number of pioneer couples who came to America in the 18^th century.
• There is little marriage to outsiders or other forms of in-migration, causing the Old Order Amish of Lancaster to form a closed gene pool
• They have large families and keep extensive genealogical records.
• They prohibit the use and abuse of alcohol and drugs, which often mask the symptoms of bipolar disorder.

“We have a total pedigree of the Old Order Amish community in a computer from the original 32 adults who came in the 1760s until in the 1970s,” said Hostetter, “so we can determine what percentage of genetic endowment any two people share.”

The research team focuses on the original “pedigrees,” or cohort. About 65 percent of the families are named Stoltzfus. Other names are King, Zook, Lapp, Beiler, Petersheim, Blank, Fisher, Miller, Glick, Esch and Smoker.

Hostetter grew up in Lancaster County in a Mennonite family and knew some Amish families with bipolar disorder. His grandfather, who was longtime moderator of , often consulted with Amish ministers. Hostetter’s father was a farmer and tobacco broker and also had much interaction with the Amish.

“My best friend, an Amish boy, in elementary school had bipolar disorder, as did his mother and grandmother,” said Hostetter. “He committed suicide at age 18 and his sister committed suicide in the 1990s.”

Hostetter was a at ��ݮ���� for two years in the late 1940s. He earned his bachelor’s degree from Goshen College in 1953. He graduated from Jefferson Medical College in Philadelphia and trained in psychiatry at Norristown State Hospital.

He joined a private practice in his home area and later formed a group practice in Hershey, where he met Egeland, who was on the faculty of . “We first spoke about using the Amish population in Lancaster County to solve the medical puzzle about inheritance of bipolar disorder in 1970,” he said.

Egeland and Hostetter both joined the faculty of the University of Miami but worked out of what they called “University of Miami, North Office” in Hershey.

Nine years ago Hostetter retired from his psychiatry practice at age 74 and moved with his wife to Charlottesville, Va. He returns to Pennsylvania about five times a year, though, to pursue his research. In December 2012 he joined Egeland there.

“We worked on ‘coding’ cases to detect particular characteristics of each of their manifestations of illness,” he said. “We have very detailed medical histories and DNA samples on over 100 bipolar patients.”

“At this point,” Hostetter continued, “we are on the verge of whole genome sequencing for 80 subjects, still attempting to locate all the specific genes involved.”

Hostetter noted that bipolar disorder is treatable and that persons with the illness can lead normal lives. “However, untreated or inadequately treated, there is still a 15 percent suicide rate, to say nothing of the suffering and turmoil these people have and put their families through,” he said.