Genetic testing has a limited role in psychiatry

An article published in the current issue of Psychotherapy and Psychosomatics analyzes the literature available on the role of genetic testing in psychiatry. Despite great expectations and marketing, the practical results appear to be modest. Indeed, even though numerous markers have been associated with psychiatric disorders, no genetic marker has yet been shown to be useful in prospectively identifying any specific psychiatric disorder. This may be due to the fact that genetic predisposition in psychiatry is thinly distributed over thousands of loci, each contributing a small effect, with considerable overlap of brain systems and shared genetic factors, sample size in most association studies has generally been too small to produce meaningful, replicable results. In addition, epigenetic and other factors that alter DNA conformation can determine whether susceptibility genes are expressed or suppressed, complicating analyses of the relationship between genotype and phenotype.

The Authors stress that descriptive diagnoses in psychiatry have multiple domains such as age of onset, constellations of specific symptoms, functioning, comorbidity, and evolution over time that assort differently in different patients in the same category to produce functionally different conditions. Genetic profiles associated with any one of these features are not likely to predict more global diagnoses. If the direct path from genotype to phenotype ends at discrete endophenotypes such as arousal, anhedonia, information processing, stress responses, inflammation and mood, rather than global diagnosis, attempts to link the latter to specific genes are likely to prove frustrating, just as descriptive diagnoses in psychiatry do not adequately consider important subtypes that exhibit different assortments of features such as age of onset, severity, progression or functioning.

The Authors conclude that the hope that pharmacogenetic testing will result in unambiguous ‘personalized psychiatry’ should not lead to quick adoption of technologies that have not yet been demonstrated to reliably predict a specific course or a need for a specific medication, the choice of which remains largely empirical. After all, genetic associations are statistical, but medical practice is personal.

Editorial: The Limitations of Genetic Testing in Psychiatry, Dubovsky S.L., Psychotherapy and Psychosomatics, doi: 10.1159/000443512, published online 5 April 2016.

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