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Researchers Discover Unique Genetic Signature for Mood Disorders in the Old Order Amish

April 20, 2023 | Heide Aungst

This Discovery Could Lead to New Mental Health Treatments

Understanding the root causes of depression, bipolar disorder, and other mental illnesses could lead to new treatments for the 300 million people worldwide who suffer from such conditions.

Now, a collaborative team led by University of Maryland School of Medicine (UMSOM) faculty affiliated with the Institute for Genome Sciences (IGS), the Program in Personalized and Genomic Medicine (PPGM), and the Maryland Psychiatric Research Center (MPRC) have found previously unknown changes in four regions of the genomes of Old Order Amish individuals which increase their risk for mood disorders.

Seth Ament, PhDThis finding was published in a recent issue of Molecular Psychiatry and could lead to a deeper knowledge of the causes of mental health illnesses in a broader population — as well as potential targets for new drug development. Researchers at the National Institute of Mental Health and the University of Pennsylvania are co-authors on this study.

What we knew prior to our study is that genetic factors account for up to 80 percent of risk for bipolar disorder and up to 50 percent of risk for major depressive disorder,” said the study’s senior author, Seth Ament, PhD, Associate Professor of Psychiatry at UMSOM and a scientist at IGS. “Most affected people in the general population inherit many risk variants, each of which has a very small effect. But in the Amish population, we were able to identify specific genetic variation in four chromosomal regions that double or triple someone’s risk for having a mood disorder.”

The Old Order Amish in Lancaster, Pennsylvania descend from approximately 400 original founders who came to the United States in the 1720s and still rarely marry outside of the group. This close genetic relationship—known as the “Founder Effect”—makes the Amish ideal for researchers to study.  Certain genetic changes, including some that can greatly increase disease risk, occur much more frequently within the group —and may be rare or even absent in the general population.

The researchers looked at data from the genomes of 1,672 Old Order Amish adults that included families in which multiple family members were affected with mood disorders. They performed statistical analyses on the participants’ genome sequences to identify specific patterns of genetic variation that were more common in affected participants, using a technique known as a Genome-Wide Association Study (GWAS).

Mark T. Gladwin, MDWhat they discovered is that genetic variation in four chromosomal regions each doubled a person’s risk for getting a mood disorder. Follow-up studies showed that the variants also influence related traits, such as slower cognitive abilities.

The researchers identified several genes at these locations that are known to influence brain development. In future studies, they hope to learn more about the specific changes in the brain by which these genes alter disease risk. Knowledge of these variants may lead to personalized approaches to treatment.

“The novel genetic patterns identified in Old Order Amish provide significant insight into how genes impact an individual’s risk of developing a mood disorder or other cognitive traits. For example, gene network analyses in this study suggest that risk genes impact the formation of synapses in the developing brain, and this may have an additive effect on neuropsychiatric disease risk," said UMSOM Dean Mark T. Gladwin, MD, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor. “We are greatly appreciative to the Amish community and research participants who have worked in partnership with our School of Medicine over the past 20 years to help us make important discoveries.”


Heide Aungst
216-970-5773 (cell)

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