Genetic testing may be a helpful tool in diagnosing autism and intellectual disability, but published data does not adequately support its use as a standard predictor of antidepressant response, James B. Potash, MD, MPH, said during a session at the virtual 2020 Psych Congress Elevateconference on the role of genetic testing in psychiatry.

There is ample reason to think that genetic variation ought to predict antidepressant response but research has shown mixed results, said Dr. Potash, who is the Henry Phipps Professor, Director and Psychiatrist-in-Chief, at Johns Hopkins Medicine, Baltimore, Maryland, and has been working in the field of genetics of mood disorders for more than 20 years.

Dr. Potash is a member of the American Psychiatric Association Council on Research, which had a task force analyze the issue in recent years. In a systematic review of pharmacogenetic tests of antidepressants, the task force found that the quality of the data provided by the tests on pharmacodynamicshow a drug affects the brainwas low, he said. However, the study, published in The American Journal of Psychiatry, found the tests provided higher-quality data on regarding particular genes related to how a drug is metabolized in the liver.

Their conclusion was at present there are insufficient data to support the widespread use of combinatorial pharmacogenetic testing in clinical practice, although there are clinical situations in which the technology may be informative, particularly in predicting side effects, Dr. Potash explained.

Similarly, an International Society of Psychiatric Genetics committee on genetic testing last year reached the conclusion that evidence to support widespread use of pharmacogenetic tests is inconclusive. But the statement also says when pharmacogenetic testing results are already available, providers are encouraged to integrate this information into their medication selection and dosing decisions, he said.

As for the future direction of genetic testing in psychiatry, Dr. Potash said there is ongoing research into its use in bipolar disorder.

A study involving 2500 people with bipolar disorder, published in Lancet by the International Consortium on Lithium Genetics, found some genetic variations were statistically significantly associated with response to lithium treatment. People with the highest Polygenic Risk Score (PRS) for schizophrenia had the lowest response to lithium treatment, and people with the lowest schizophrenia PRS had the highest response to lithium treatment. In addition, a paper recently published in Molecular Psychiatry found that people with bipolar disorder who had the lowest PRS for depression were 75% more likely to respond favorably to lithium, compared with those with the highest depression PRS scores.

Dr. Potash also spoke about the importance of a more traditional genetic research tool: collecting a detailed family history from a patient.

It has been known for a long time but its not always implemented, he said, noting that familial recurrence risk has been analyzed for more than 100 years.

For example, he explained, if one parent has schizophrenia and no siblings or second-degree relatives do, a child has a 6% risk of developing schizophrenia. But if one parent, two siblings, and a second-degree have the disorder, the relative the risk of a child inheriting it is 36%.

That kind of information is important, he said. Very important. Its valuable.

Terri Airov

References

Amare AT, Schubert KO, Hou L.,et al.Association of polygenic score for major depression with response to lithium in patients with bipolar disorder.Molecular Psychiatry. 2020 March 16;[Epub ahead of print].

Genetic Testing Statement. International Society of Psychiatric Genetics. Accessed July 15, 2020.

Hou L, Heilbronner U, Degenhardt F, et al. Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study. Lancet. 2016;387(10023):1085-1093.

The role of genetic testing in psychiatry. Presented at Psych Congress Elevate: Virtual; July 26, 2020.

Zeier Z, Carpenter LL, Kalin NH, et al. Clinical implementation of pharmacogenetic decision support tools for antidepressant drug prescribing. The American Journal of Psychiatry. 2018;175:873886.

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The Limitations and Promise of Genetic Testing in Psychiatry - Psych Congress Network