Testing Now Considered Essential to Some Treatment Paradigms
Upon completing his psychiatric residency at Columbia University in New York City some 40 years ago, John Nurnberger Jr., MD, PhD, took the road less traveled. He indulged his curiosity about the genetics of psychiatric disorders by taking a medical officer position at the National Institute of Mental Health.
“Although psychiatric genetics was very interesting to me as a scientist, it was not something that had a lot of clinical relevance at that time,” Dr. Nurnberger recalled. “Psychiatrists who were not heavily invested in understanding the biochemistry of these disorders may not have chosen to give a lot of attention to this field because it didn’t make any difference for them in their practice, apart from the fact of the familial concentration of disorders.”
“The actual mechanics of gene differences in patients and controls was not something that was important for practicing psychiatrists to know. It just wasn’t something that came up,” he said.
But times change.
“Now it does,” Dr. Nurnberger added. “That’s the difference.”
Today, some patients are as apt to arrive in the clinic with genetic test results from 23andMe or a pharmacogenomic testing company as they are a symptom list. Consequently, mental health providers may quickly find themselves in uncharted and uncomfortable terrain, not quite sure of the role genetics is ready to play in modern-day psychiatry.
Dr. Nurnberger will brief providers on the current clinical relevance of psychiatric genetics during his “What Should a Psychiatrist Know About Genetics?” talk at Psych Congress. A distinguished professor of psychiatry at the Indiana University School of Medicine in Indianapolis, Dr. Nurnberger has remained involved in psychiatric genetics research throughout his career. For the past several years, he’s chaired an International Society of Psychiatric Genetics (ISPG) committee tasked with bridging the gap between psychiatric genetics evidence and its role in everyday psychiatric practice.
“The ISPG Residency Education Committee consists of 10 to 15 investigators in psychiatric genetics from the United States and other countries who try to collate the literature and sort out what would be most useful for psychiatrists just entering practice to know,” Dr. Nurnberger explained.
Over the past year, the committee has published two papers—one in the Journal of Clinical Psychiatry1 and the other in JAMA Psychiatry2—explaining specific genetic findings applicable to current psychiatry practice.
“In child-onset disorders, particularly autism spectrum disorders and intellectual disability, genetic testing is not only useful but also regarded as an essential part of the evaluation,” explained Dr. Nurnberger.
“Probably 10% of people with autism spectrum disorders and maybe up to 50% of individuals with intellectual disabilities have specific genetic abnormalities that are called copy number variants, which are small deletions and duplications in their genome,” he said. “These alter the evaluation and may give a specific genetic answer that explains a lot of the pathology and guides further evaluation of other organ systems, and in some cases, management and treatment.”
Dr. Nurnberger’s session also will coach providers on when and how pharmaco-genomic testing can be used to influence treatment decisions. For example, a genetic test may reveal a patient with major depression to be an unusually fast, or slow, metabolizer of certain antidepressants and may signal the need for a medication adjustment.
Just as important, Dr. Nurnberger will review situations in which genetic testing is not yet useful in guiding current clinical treatment—such as with adult-onset schizophrenia or bipolar disorder—despite claims supporting the use of direct-to-consumer genetic testing.
“You can imagine how a patient would respond after reading something in the newspaper or seeing something on TV. Then they receive a genetic test result, and they’re ready to go with a new plan of management and treatment,” he said. “You have to caution people not to get carried away. In the majority of cases, the information is incomplete or just not substantiated by the genetic literature.”
In addition to addressing the here and now, Dr. Nurnberger will provide session attendees with a glimpse into the future. His presentation will address how polygenic risk scores, which are currently used in research, as well as DNA sequencing, may one day be used in clinical practice.
Over the span of Dr. Nurnberger’s 4-decade career, psychiatric genetic research has advanced significantly—from studies focused on candidate genes thought to be associated with certain disorders to single experiments that scan the entire genome for specific gene variants.
“Technology now enables us to identify gene variants associated with psychiatric conditions without any bias or pre-existing hypotheses about how the diseases are generated from brain abnormalities. We no longer have to base our work on theories from older studies that gave us ideas about how illnesses work and possible treatments for them,” he said. “Instead, we can do an unbiased examination of all the possibilities.”
With his session, Dr. Nurnberger aims to get genetics onto psychiatrists’ radar—not merely because the subject is interesting, but because it’s practically relevant.
“Genetics is no longer peripheral,” he said. “Hopefully psychiatrists will come away from this session understanding that genetics is an area they ought to pay more attention to.”
1. Nurnberger JI Jr, Austin J, Berrettini WH, et al. What should a psychiatrist know about genetics? Review and recommendations from the Residency Education Committee of the International Society of Psychiatric Genetics. The Journal of Clinical Psychiatry. 2018 November 27;80(1):17nr12046.