A Productive Life for Psychiatrist Who Stayed Close to His Roots

Abram Hostetter, M.D., found a career-long research project right down the road from where he grew up on a dairy farm in rural Pennsylvania.

Aaron Levin

Or maybe the project found him.

Hostetter was raised in a Mennonite family on that farm near Gap, Pa., the second of 12 children. By age 10 he knew he wanted to be a doctor, he recounted in a recent interview. After graduation from Goshen College, a small Mennonite school in Indiana, he went to Jefferson Medical College in Philadelphia.

His interest in psychiatry was stimulated by two childhood associations, he said: a grandfather who became mentally ill secondary to pancreatic cancer and a high school friend with bipolar disorder.

After training at Norristown State Hospital, he set up a practice in Hershey, Pa., and drew a number of Amish patients, perhaps because of his local roots in Lancaster County. Around 1970, he began an association with Janice Egeland, Ph.D., a psychologist who had been studying health care usage among the Amish. Egeland lived with an Amish family while doing her research. A daughter in the house had gone to high school with Hostetter and helped connect the two.

Hostetter and Egeland eventually collaborated with researchers from eight schools of medicine in the United States and Canada to begin the Epidemiologic Study of Affective Disorders Among the Amish in 1976. Better known simply as the “Amish Study,” the research sought to examine the etiology, diagnosis, and epidemiology of affective disorders among the Amish.

The Amish people of central Pennsylvania serve as an unusually homogeneous study population for genetically oriented biomedical researchers. They are descended from just 30 founding progenitors who arrived from Germany in the 1700s. They do not admit converts and have a high birth rate. That has led, in some family lines, to higher-than-random rates of some heritable illnesses, including bipolar disorder.

The Amish are also culturally stable and culturally isolated, lessening the effects of many environmental influences on their lives and health. They resist much modern technology or limit its use.

“Children are not exposed to television, rock music, or video games,” said Hostetter. “Their separation from the ordinary world insulates them from many of the stresses of modern life, and they have excellent family support.”

As breeders of livestock, they also have a functional understanding of genetics. They saw in their families behavioral patterns related to bipolar disorder and even without scientific training, they knew there was a heritable component, said Hostetter. As one woman told Egeland, “Das ist in blut”—“It’s in the blood.”

They also are close observers of each other. So when Egeland and Hostetter interviewed subjects, their respondents were often able to provide detailed descriptions of symptoms, sometimes going back generations.

Although it may seem contradictory to outsiders, given their aversion to modern technology, the Amish are not averse to modern medicine, said Hostetter. They respect learning and expertise. Once a diagnosis is established, they are treatment compliant.

“They come from an authoritarian culture, and if a doctor says ‘take your medicine,’ someone is there to see that you take it,” said Hostetter.

The initial goal of the Amish Study was to identify all cases of mental illness among the Amish population using hospital records along with community informants from each church district. Each district included 30 to 50 families, providing fine-grained coverage. Ultimately, the team focused on two extended families that had produced an unusually high number of people with bipolar disorder and other psychiatric diagnoses.

Ultimately, a combination of genealogical work with clinical diagnosis and careful case review by a team of psychiatrists established the heritability of bipolar disorder. With that in hand, Hostetter, Egeland, and their colleagues moved on to track higher-risk children in families with one bipolar parent and compare them with children in unaffected families.

“We observed that there was a profile of symptoms that appeared before they became psychiatrically ill,” he said. Furthermore, none of these Amish children met full clinical criteria for bipolar disorder before age 12.

The at-risk group exhibited more anxiety, inattention, excitability, hyperalertness, mood changes, and somatic complaints. At the 10-year follow-up, children of a bipolar parent showed increased energy, decreased sleep, problems with thinking or concentration, and excessive and loud talking, compared with controls.

The researchers produced a series of papers on these prodromal patterns between 2000 and 2012, following the children as they grew up and adding siblings to the study as they were born.

“We thought this was important information for pediatricians and family physicians because it could help them differentiate those symptoms from ADHD,” said Hostetter. “Clinicians should ask about a family history of bipolar disorder before they consider use of stimulants for ADHD.”

Hostetter served not only the Amish of Lancaster County, but his profession as well. He is a former member of APA’s Board of Trustees and past president of the American Psychiatric Association Foundation.

Both Egeland and Hostetter are retired now, but work with the Amish continues under a team led by their collaborator, Edward Ginns, M.D., Ph.D., a professor of psychiatry at the University of Massachusetts.

This new wave of research drew on a longstanding observation that in some Amish families there was an unusual number of individuals either with bipolar disorder or with Ellis-van Creveld dwarfism, but none with both.

That suggested that whatever genetic mutation causing Ellis-van Creveld in the Amish might also confer protection from bipolar illness. Further genetic investigation, Ginns and colleagues reported in October 2014, found that the mutation acts by disrupting sonic hedgehog signaling, which is thus implicated in the underlying pathophysiology of bipolar affective disorder. Sonic hedgehog is a protein that plays a role in the development of the central nervous system.

Their discovery may open doors to treatment of bipolar disorder, since sonic hedgehog signaling antagonists already exist and are being tested in clinical studies for the treatment of cancer.

The Amish gained something from the research and the closer contact with the health system, said Hostetter. In one pedigree, 60 individuals with bipolar illness from older generations had been hospitalized. However, in more recent generations, 17 were identified with the disorder, and all had been treated solely as outpatients.

His research also had a profound impact on Hostetter, whose training was heavily psychoanalytic, like most of his generation.

“It helped me become more biologically oriented,” he said. “I now think that mood, temperament, and abilities are genetically determined, that we are shaped by the genes we carry. Experiential factors are involved but, still, genetics are basic.” ■