SAN DIEGO—Psychiatrists need more knowledge of genetics because patients are coming to them armed with questions, and often their own genetic test results. But provider training has lagged, and the use of genetic data to inform treatment remains a work in progress, Indiana University Professor of Medicine John Nurnberger Jr., MD, PhD, said at Psych Congress 2019.
Still, Dr. Nurnberger told a session audience that genetic research evidence, particularly in pharmacogenomic analysis of medication options, continues to grow more positive. While it may be too soon to recommend routine ordering of patient genetic tests for diagnosing a disorder or prescribing a treatment, many potential applications merit psychiatrists' attention, he said.
Dr. Nurnberger chairs the International Society of Psychiatric Genetics (ISPG) Residency Education Committee, tasked with determining what information about psychiatric genetics would be most useful to psychiatrists entering the profession. “Most residents get less than three hours of genetics training in their residency,” he said.
The information gained from genetic tests will be complex, he warned, because multiple genetic factors contribute to the most common psychiatric disorders. Genome-wide association studies have identified more than 250 gene variants in schizophrenia and more than 50 in bipolar disorder, for example. These variants are generally associated with a 10 to 30% increased risk for the disorder.
More from Dr. Nurnberger: The Current and Future Roles of Genetics in Psychiatry
The discovery of human leukocyte antigen (HLA) polymorphisms has pointed to the increased relevance of immune mechanisms in schizophrenia, Dr. Nurnberger said. Testing for HLA variants also is now recommended for assessing a patient's risk of developing the serious skin reaction Stevens-Johnson syndrome when prescribed the mood stabilizers carbamazepine or oxcarbazepine.
Pharmacogenomic testing has therefore been deemed necessary in some circumstances, but it is not yet widely indicated, Dr. Nurnberger said. For informing choice of an antidepressant, it probably should be considered only after 2 or more failed antidepressant trials in a patient, he recommends. For diagnosing a psychiatric disorder, it might come into play only in circumstances such as when multiple siblings are affected by an illness, he said.
Dr. Nurnberger added, however, that demand for genetic testing will continue to grow because the results can make a difference for patients and families, in areas ranging from informing family planning to allowing surveillance for known comorbidities such as cancer risk.
Results from commercially available genetic tests must be interpreted cautiously, Dr. Nurnberger pointed out, as most companies have not conducted controlled trials of their tests and, none have been studied independently, and the research that has been completed has shown mixed results. A trial examining the Assurex test did not show that use of congruent medications based on a patient's genetic profile led to significant symptom improvement, but switching from an incongruent medication to a congruent one during treatment did generate an overall benefit, according to the presentation.
Dr. Nurnberger urged the audience to keep an eye on the potential applications of the relatively new polygenic risk score testing, which assigns individuals a total risk score based on the number and value of risk variants they carry. Areas that polygenic risk score could inform in the future include prognosis of first-episode care for depression and psychosis, he said.
“What should a psychiatrist know about genetics?” Presented at Psych Congress 2019: San Diego, CA; October 4, 2019