Genetics & Genomics

August 3, 2022

Embryo screening for mental illness questioned

Report finds polygenic embryo screening (PES) does not provide an accurate measure of the risk of developing psychiatric disorders later in life.

In vitro fertilization (IVF), fertilizing eggs in the laboratory, not only enables otherwise infertile couples to conceive children but, by screening embryos before implanting them in the womb, to avoid passing severe and fatal inherited conditions like Tay-Sachs disease to their offspring.

Companies also have begun to screen embryos for the risk of developing complex diseases, including psychiatric disorders, which result — in part —from the “polygenic” interaction of many genes.

But just because polygenic embryo screening (PES) is possible doesn’t mean it provides an accurate measure of the risk of developing psychiatric disorders later in life, according to a report Aug. 2 in the journal The Lancet Psychiatry written by 18 members of the International Society of Psychiatric Genetics (ISPG).

“We are concerned that these tests are being marketed with limited empirical data behind them and virtually no scientific or ethical discussion,” said first author Todd Lencz, PhD, a professor in the Institute of Behavioral Science at the Feinstein Institutes for Medical Research. “Without more research, it is unlikely that medical providers and the general public will have sufficient understanding to evaluate the pros and cons of this technology.”

“The potential implications of polygenic embryo screening are far-reaching, and worthy of much wider public debate,” added co-author Lea Davis, PhD, associate professor in the Division of Genetic Medicine at Vanderbilt University Medical Center and a member of the ISPG board of directors. “The scientists conducting the basic research that these companies are leveraging have an obligation to take part in that discussion.”

Elaborating on a statement released last year by the ISPG, the paper calls for additional research, uniform oversight, and rigorous consideration of the clinical, social, and ethical implications of using polygenic pre-implantation genetic screening and polygenic risk scoring for psychiatric disorders.

“First,” the authors point out, “polygenic risk scores do not determine whether a person will develop a condition. They measure just one of many possible risk factors.”

Polygenic risk scores also are not specific to a single condition or trait. There is some suggestion that bipolar disorder, characterized by extreme mood swings, may be linked to above-average intelligence and creativity, traits that also may be detectable by pre-implantation screening.

Selecting embryos with a low polygenic risk score for bipolar disorder thus “could result in reduced creativity in offspring,” the authors write.

Communicating risk in relative versus absolute terms is challenging and time-consuming. The standard IVF practice may not have the expertise necessary to help prospective parents make informed decisions.

In many countries there is no regulation or oversight of PES. Whereas the United Kingdom permits pre-implantation genetic testing only for a defined list of monogenic diseases, “there is no regulation about which conditions or traits can be screened for in the USA,” the authors write.

PES also raises ethical concerns for physicians who, in addition to their traditional focus on treating and preventing illness, now would be trying to “enhance” certain traits. This aspect of PES recalls the eugenics movement of the early 20th century, which sought to improve the genetic “quality” of humankind through science.

The horrors of racial cleansing unleashed by the Nazis in the 1930s are well known. But in the United States, eugenics-inspired compulsory sterilization of the “mentally unfit” persisted well into the 1950s.

By emphasizing the genetic explanation for mental illness, the authors added, PES may fuel prejudice that people with psychiatric diagnoses are dangerous and encourage discrimination against them.