Amish genes could hold the key to treating mental illness

An Amish family in Lancaster, Pennsylvania, has known for some time that their son was deeply troubled and unhappy. Now in his early twenties, he was unsuccessful and had not found his way as a productive member of their old-order Amish farming community of 40,000. The family faced many obstacles to improve their son’s mental health.

When such cases reach a crisis point, the Amish community provides support groups for people whose mental illness is interfering with their ability to function, Susan Shaub, a registered nurse and care coordinator for the Amish Research Center (ARC) in Lancaster, told The Daily Beast. They assist them in finding work, usually within the community, that matches their level of functioning. They help them handle finances and host benefit sales to raise money to cover expenses.

Often these support workers also take the individual involved in medical research studies on mental health at the ARC.

“Amish family members are more likely to participate in a study if they know some of their siblings participated,” said Shaub, who has worked at the ARC since 2004. “People with siblings who have significant mental health issues often share in the hope that research will lead to improved treatments.”

For nearly half a century, medical researchers working with the Amish have made important breakthroughs. According to Seth Ament, a geneticist and neuroscientist at the University of Maryland School of Medicine in Baltimore, studies among the Amish have led to the discovery of many genes and genetic associations relevant to cardiometabolic traits, bipolar disorder, brain aging and autism. One of the genetic variants found in the Amish population, Ament added, is linked to an increased risk of long QT syndrome, a form of abnormal heart rhythm that can lead to sudden death from a heart attack, sometimes without prior symptoms.

“What’s unique about the Old Order Amish is that because it’s essentially a family of 40,000, the burdens associated with these diseases are shared throughout the family,” Ament told The Daily Beast. “Because the Amish family is so large, there are opportunities among the Amish to develop precision medicine strategies that could be applied to the broader population in the future.”

A study recently published in the journal Molecular Psychiatry has improved scientists’ understanding of the genetic causes of depression, bipolar disorder and other mental illnesses, which affect approximately 300 million people worldwide.

“What we knew before our study is that genetic factors account for up to 80 percent of the risk of bipolar disorder and up to 50 percent of the risk of major depressive disorder,” said Ament, co-author of this new study. “Most affected individuals in the general population inherit many risk variants, each with a very small impact. But in the Amish population, we were able to identify specific genetic variations in four chromosomal regions that double or triple the risk of mood disorders.” These genomic changes were previously unknown to the researchers.

These revelations are the culmination of nearly a decade of work by Ament and his team analyzing genome-wide association studies in Old Order Amish patients at the university’s Amish Research Clinic. They can lead to a deeper understanding of the causes of mental illness in a broader population – and also to potential targets for the development of new drugs.

Geneticists consider this particular Lancaster Amish community a “founder population,” meaning they are direct descendants of a founding community of just a few people. In this case, the Lancaster Amish descend from 400 people who immigrated to the United States from Western Europe (mostly of Swiss-German descent) in the late 18th century.

For religious reasons, the Amish only marry within their community. As the original population has grown to 40,000 today, genetic variation within the population continues to be primarily due to the original 400 founders.

In other words, the members of this Lancaster Old Order Amish represent an extremely large family of about 40,000 members.

“That’s one of the interesting things about the population,” Ament said. “They’re very close to us and yet they’re a very different group genetically and culturally.”

Because genetic variation within this community is so low, Jonathan Pevsner, director of genomics research for the National Institutes of Mental Health, said there may be certain DNA variants in the genes of Amish individuals that are easier to spot.

“We think the study of mood disorders among the Amish is particularly helpful,” Pevsner told The Daily Beast. “We also support research into other founding peoples around the world, but in the case of the Amish it has been extremely productive.”

Ament noted that the Amish who participate in the studies believe the research is mutually beneficial to their community, so they view the work as a reciprocal relationship.

“For religious reasons, the Amish don’t use some modern technology, but they are very smart and understand that people who are members of the founding peoples are at risk for certain rare diseases,” Ament said. “They also understand that their genetics have value to the wider community, so they enroll in these studies and allow us to study their families, and the research is supported by their community leaders.”

Although the ARC was first established in 1994, Ament traced the origins of these Amish studies even further to Victor McKusick, widely considered the “father of medical genetics.” McKusick, who died in 2008, had begun including Amish patients with bipolar disorder in his genetic studies at the Johns Hopkins School of Medicine as early as the 1970s, uncovering the recessive gene links to several disorders. .

Ament said he was inspired by McKusick’s sensitive but focused approach to studying Pennsylvania’s Old Order Amish as a group with a relatively isolated gene pool. He realized he could use their medical and genetic history to quickly identify the genes responsible for their inherited physical abnormalities and disorders.

At the time, researchers didn’t know much about the genetic architecture of diseases, and there was hope that there might be a single mutation that could explain mental disorders.

“I don’t want to say that our study was the culmination of Dr. McKusick’s work is, however, a significant advance in the study of mood disorders among the Amish,” Ament said. “We are making real strides in understanding the mechanisms in the brain that contribute to diseases like bipolar disorder and depression, which over time will most likely lead to more precise methods of treating these diseases.”

Shaub told The Daily Beast that the clinic has always carefully approached the issue of mental health studies in the Amish community to ensure the confidentiality of everyone participating in a study. From the beginning, the clinic’s nurses worked closely with Amish liaisons to open doors and recruit patients. There are currently 17 liaisons involved with eight active studies.

“Over the years, the community has come to realize that while these ladies are part of the community, they are bound by our standards for HIPPA patient privacy,” she said. “People know that in the presence of our liaisons they can feel comfortable exchanging things and this is kept confidential.”

One of the liaisons, Lavina Ebersol, who helped recruit patients for Ament’s study, told The Daily Beast, “You could tell the people who might have mental health issues because they were just sitting there a little quieter and hesitant, and those who might have suffered from it in their families were a little more open and willing to talk about it and participate in the study to do whatever they could to help their loved ones.”

While they don’t know what the end results will be because the ARC conducts long-term research studies, Shaub said the Amish participants see mental health problems in families from generation to generation and want to help improve the situation for the next generation, if possible.

She added that there may not be any immediate mental health benefits for patients, but they are treated well, such as being given breakfast if they are fasting before blood tests. Everyone gets a blood test to test their cholesterol levels and their risk of diabetes or cardiovascular disease — “just to give them a little piece of something for what they’ve done for us,” Shaub said.

The ARC is just part of a larger network of similar research centers in the Midwest. The clinic is currently developing two joint studies that it expects to start soon with Das Deutsch Clinic (DDC) for children with special needs in Middlefield, Ohio, east of Cleveland. According to Heng Wang, one will study genetic diversity in the general population and the other will study cardiomyopathy, Medical Director of the DDC. Unlike the ARC, the DDC clinic examines and treats patients suffering from rare genetic disorders.

“Our work focuses primarily on monogenic diseases involving a single gene, while Dr. Ament’s study involves complex diseases in which multiple genes play a role, often together with environmental factors,” Wang said. “Our patients, like everyone else, could also have mood disorders in addition to their illness and benefit from his study.”

In a study published in 2011, Wang identified the gene that causes a rare congenital condition called glucose-galactose malabsorption in the Amish population. Babies and children worldwide suffering from this disease cannot absorb enough sugar. As a result, the unabsorbed sugars in the baby’s intestines cause severe diarrhea and dehydration, which can be fatal if left untreated, and many babies and children died from the condition. In addition, these babies cannot be breastfed because breast milk contains lactose — a sugar — that cannot be adequately absorbed. Working with other researchers, Wang and his team found that a simple treatment is to remove sugar from children’s diets or infant formula for newborns.

At the DDC, Wang said they now diagnose two to five babies with the disease each year through DNA testing.