Genotyping and the Future of Psychiatric Treatment

The scenario of a patient who has tried multiple drugs and had little positive effects is all too common for physicians. However, genetic testing could offer an inside look for clinicians when it comes to treating patients with difficult-to-manage psychiatric symptoms. Genotyping, or the sequencing and annotating of an individual’s genome, has progressed significantly from the days of the Human Genome Project. It is now possible for patients to have their genome sequenced and bring their own genetic information to their clinician. Consequently, more often than not, they are expecting their physician to provide some type of genetics-based explanation or answer about their mental health problems.

According to Stephen M. Stahl, MD, PhD, adjunct professor in the Department of Psychiatry, University of California, San Diego School of Medicine, and director of Psychopharmacology for the California Dept. of State Hospitals, “The current diagnostic strategy is to attempt to link symptom domains that cut across psychiatric disorders to inefficient information processing in specific brain circuits’ decisions.” Then, drug interactions or lack thereof can be determined and a new treatment route may be chosen based on the information. While Stahl noted that “genetic testing as a clinical tool is still in its infancy,” he also added that, “it has the potential to inform treatment.”

An example of genetic information informing treatment choice relates to the SLC6A4 serotonin transporter gene. According to Stahl, the 5-HTTLPR S-allele of this gene is potentially associated with “an increased risk of developing depression under stress.” Next, Stahl noted that “patients with treatment-resistant depression with the S-allele or another type, the L(G)-allele, may be less likely to respond to and more likely to have side effects on an SSRI/SNRI,” when SLC6A4 was examined in terms of antidepressant efficacy. He suggested that treatment proceed with another class of medication.

In another example, Stahl said patients with treatment-resistant depression (TRD) with a Val ^108/158 Met substitution in the Catechol-O-methyltransferase enzyme theoretically may have lower dopamine and thus cognitive and working memory problems. He said that genetic information can tell us that such patients “may be less likely to respond to an SSRI,” and may benefit from being placed on another antidepressant that theoretically boosts dopamine.

Genotyping can also offer insight into potential phenotypes such as schizophrenia. Stahl noted that genetic testing tells us that, “Homozygous (TT) genotype of the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism plus a 5 µmol/L higher homocysteine level is associated with a 70% higher risk of schizophrenia.” While this means that the genetic risk for an individual is higher in terms of schizophrenia, it’s not a guarantee‑‑it’s a potentiality. Stahl reminded the audience that “genes do not code for psychiatric disorders or psychiatric symptoms.”

According to Stahl, “caution is essential when bringing genetic testing into the selection of treatment in clinician practice.” The main reason is that the research is cutting edge and there is still plenty to learn. Stahl would like this information to be used as a suggestion when it comes to treatment selection by clinicians and as a potential road of information on which doctors can determine a new route to take in terms of treatment and drug types.