Hunt for Biomarkers Intensifies But Still in Infancy

Rutgers New Jersey Medical School

Psychiatry has long been awaiting the arrival of the biomarker—a hard piece of data that can provide a diagnosis, predict a treatment response, or just give us some type of answer. Unfortunately, the search has been relatively fruitless, with fits and starts along the way.

Though there has been many promising candidates such as the dexamethasone suppression test for the diagnosis of depression, cerebrospinal 5-hydroxyindoleacetic acid (5-HIAA) metabolite in depression or sociopathy, and the brain-derived neurotropic factor (BDNF) or various cytokines in schizophrenia and depression, none have risen to the level of sufficient sensitivity and specificity to qualify as clinically useful. Sure, we have breathalyzers for alcohol levels and all kinds of fancy toxicology testing, but those numbers only provide data on recent use. We still do not have a test that can diagnose the disease or predict its course.

Drug-gene testing, or pharmacogenomics, is one of the latest players in the game. It involves characterizing a patient’s gene variants to determine how he or she will respond to a specific medication. Data such as gene expression or single-nucleotide polymorphisms are correlated with drug absorption and metabolism, thus allowing prediction for an individual’s response to a particular drug. A variety of private companies has sprouted up in recent years, promising to use this new science to improve patient outcomes and decrease guesswork in selecting medications. Their presence is now ubiquitous in the exhibitor halls at clinical and scientific conferences. But do they really have anything to offer?

I think it depends on our expectations. While many of these companies have websites that make big promises, they are usually offering an assessment of a patient’s drug-metabolizing enzymes. While the answer to the question, “What kind of metabolizer is my patient (poor, extensive, or ultra-rapid)?” may offer useful information, it is not necessarily needed in clinical practice when one is doing a thorough medication titration.

Another service that is being offered is allele testing. It has been shown that the presence of the A118G allele of the mu-opioid receptor gene might predict a better treatment response to naltrexone among patients with an alcohol use disorder. However, this does not mean that patients with other alleles of the gene will not respond to naltrexone—in fact, some of these patients respond just as well. So, if you knew your patient did not have the A118G allele, would you still decide to give naltrexone a try?

It seems that we have a long way to go before we can incorporate pharmacogenomics into our daily clinical practice in a meaningful way. We are still on the hunt for some solid biomarkers and improvements in psychiatric diagnosis. And yet, given the staggering complexity of the brain and the fact that psychiatry is still a young science, I think we can give ourselves a break that we haven’t cracked the code quite yet. ■