Biomarkers in Psychiatry: Communication Opportunities and Obstacles

A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention (1). Researchers hope that identifying a biological or physiological marker for a psychiatric disorder, rather than relying on behavioral symptoms and signs (as does the current Diagnostic and Statistical Manual of Mental Disorders), will provide a more precise means of diagnosis and deepen their understanding of etiology and treatment (2). For example, psychiatric biomarkers could be used to predict the risk for developing a particular disorder.

Genetic screening and neuroimaging are the main techniques for identifying biomarkers in psychiatry. If these were reliable and valid for predicting the onset of disorder, children could be screened before symptoms appear. Treatments that decrease risk factors and optimize resilient factors might then be initiated to improve prognosis (2–4).

Biomarkers are typically used as a means of estimating the probability that a disorder is present or will develop. The biomarker is not the cause of the disorder. Algorithms that bundle risk factors might be powerful predictors of psychopathology, but they still represent groupwide statistical probabilities. For a specific individual, the predictive value of the biomarker is less accurate (2, 4, 5). This leads to social and ethical dilemmas. For example, risk profiling for psychiatric disorders among children could lead to increased stigma toward the child identified as at risk and might adversely affect his or her sense of self and life trajectory—an effect termed “risk identity” (2, p. 204). Society might alter education, law, and policy to address the “risk” and “potential” psychopathology—in positive or in damaging ways.

Identifying high-risk individuals or groups has the potential to help direct more attention and resources to the problems people in these groups encounter. It also has the potential to stigmatize them. For example, if a genetic biomarker identifies children from ethnic minorities as being at risk of problem behaviors or psychiatric conditions, this might build on existing biases about the links among race, genetics, and behavior. Might this result in a self-reinforcing destructive effect of genetically profiling young people of a particular race or ethnicity? The ethical, economic, legal, and social issues involved in genetic biomarker research have been referred to as EELS (6, 7).

Clinical Vignette

Ms. Jackson walked into the office with her 13-year-old son, Mark. She handed Dr. Fuentes an envelope as she shook the doctor’s hand in greeting. Ms. Jackson smiled tensely. Mark slouched in behind her, wearing an emotional mask of practiced bored indifference. Dr. Fuentes guessed they had fought and that Mark was not here of his own accord.

They sat down, and introductions were made. Dr. Fuentes explained that an initial evaluation with an adolescent typically includes an introduction and clarification of the reason for the consultation together. She added that she wanted to meet with Mark and his mother separately to get a history and to have a chance to understand the issues from each person’s perspective.

“So,” Dr. Fuentes proceeded, “what brings you to see me, Mark?”

“My mom,” Mark answered wryly.

“Yes. Shall I assume you didn’t want to come?” Dr. Fuentes inquired curiously.

“Wow, you can read minds. Amazing,” Mark replied sarcastically.

Ms. Jackson burst into the conversation. “Mark has an attitude. He never listens. And I found him smoking pot the other day. At 13! As you can see, he is rude. Well, I thought maybe it was just adolescence, you know. He is my oldest, so I didn’t really know. So I got him tested to see if he is a sociopath.”

Dr. Fuentes looked quizzical. “Which test is that?” she inquired.

“You know. The blood test. It is an add-on for GenieMe, the genetic testing that tells you about your ancestors and possible genetic diseases. He has the sociopath gene,” Ms. Jackson reported, as tears welled up in her eyes. “His dad’s in jail—they say he’s a sociopath, so I had Mark tested. I don’t know what to do,” Ms. Jackson said, tears beginning to spill over and run down her face as she reached for a tissue.

“Mom,” Mark interrupted. “I don’t even know why you made me get that stupid test. I told you. I do what I want, and no oxymoron gene, or whatever it was, makes me do these things.”

Dr. Fuentes nodded. “Ms. Jackson. Mark. I am not exactly sure which test you had—probably for the monoamine oxidase A gene. One thing I do know is that this test—called a biomarker—is only one of many components of behavior and personality. It seems very scientific—a lab test and gene. But people are much more complex than that.”

Dr. Fuentes thought further. “Let me draw a picture of how I think about the gene tests. Let’s say this is Mark,” she said, starting a simple drawing. “Don’t you think it looks like you?” Dr. Fuentes remarked playfully. “So, this half on the right is the environment and all of the effects of experience on your behavior. On the left are genetic influences. Genes control how we look, our temperament—how easygoing or shy or bold we are. So, let’s call this little foot part the biomarker. Maybe it makes a difference, maybe not. It depends on a lot of things, including experience. But there’s a whole lot of other area that isn’t the biomarker. That can make the most difference. So, that’s the part that can be the fun, handsome, sarcastic, and snarky teenager of today—that can grow up to be a fun, handsome, hopefully not quite so oppositional young man.”

Dr. Fuentes looked up from the drawing. “Don’t you think I should have been an artist? Looks sort of like a Picasso, don’t you think?”

For the first time, Mark showed a hint of a smile, before looking down to reaffix his bored and uninterested façade.

His mother sighed. “Okay, so maybe he won’t be a sociopath?”

“He smiled at my joke. He can’t be all bad,” Dr. Fuentes said playfully again.

Mark and his mother both smiled this time—and even at each other.

Communication About Biomarkers: From EELS to Understanding

Biomarkers are becoming commercialized, such as genetic-screening (e.g., 23andMe) and brain-scanning services. Individuals may gain information about their risk profile for numerous diseases and disorders, as well as information on personality and behavioral types (2). This information may be helpful, and patients have the right to access information provided by these products. However, this genetic testing raises critical questions of how individuals who might test positive for disease risk view and understand the genetic information that they receive (8).

Studies suggest that individuals at risk for disorders for which definitive tests exist, such as Huntington’s disease, frequently misunderstand the genetic mechanisms, risks, and tests, even after genetic counseling and explanation (9). The issue of genetic risk taps into a highly subjective personalizing process, which may distort understanding of the facts presented (10). Identifying a risk biomarker for a psychiatric disorder also taps into the affect-laden personalizing process. Biomarkers, which are perceived as objective and precise, might have greater persuasive power than is warranted by their predictive power. The patient or his or her parents might hear results of biomarker testing as a diagnosis, a predictor, although current biomarkers do not have that degree of accuracy or specificity (5).

For example, several studies have suggested that a variant of the monoamine oxidase A gene may be associated with risk of antisocial behavior, but only when there is a history of adversity in early childhood (11, 12). Identifying a child with this risk biomarker might change how others treat the child and lead to a “self-fulfilling prophesy” of behavior that accommodates expectations. Thus, communication of biomarker results must take into account the affective impact, as well as the cognitive understanding, of how the results might affect the patient (13, 14).

Communicating and explaining biomarker-risk results requires skill, engagement, and ongoing open discussion about the complexity and multifactorial nature of health and psychopathology. Patients who feel cared about and understood are able to use that empathic engagement to regulate emotions and to digest the information discussed. Epstein and Street (15) have identified a framework for patient-centered communication that includes the following functions: fostering the therapeutic relationship, exchanging information (gathering and providing information), making decisions, enabling disease- and treatment-related behavior, responding to emotions, and managing uncertainty.

In the specific case of communicating results of biomarker testing, these steps require multiple skills: the skill of engaging the patient; of breaking bad news; of explaining complexity and ambiguity regarding the import of biomarker results related to psychiatric disorders; of attending to issues of culture and stigma related to familial disorders or psychosocial risks; of maintaining empathic attunement; and of considering EELS that might be relevant. Ethical issues connect to a potential increase in stigma—particularly as it relates to building on biases related to ethnic or racial minority groups being at risk for psychiatric, substance, or behavioral disorders. Economic issues and psychosocial adversity interact with mental health in multiple dimensions—stressed individuals are at higher risk for psychopathology, and economic issues might affect the access and affordability of genetic testing and evidence-based treatments for individuals at risk for a disorder. Legal issues might relate to who owns the biomarker information, whether it can be accessed by insurance companies and might lead to an increase in premiums or loss of insurance for a “pre-existing illness,” and how to ensure informed consent.

As always, “First, do no harm” is an ethical precept for all testing and interventions. Biomarkers for psychiatric disorders are most useful when identified prior to the onset of the disorder and when evidence-based early interventions or treatments are anticipated to improve prognosis. The social impact for an individual with a risk biomarker, as well as for educational and other institutions, needs to be considered, and advocacy might be indicated to ensure access to appropriate services and social supports (6).

One area of biomarker testing that is becoming increasingly common is the use of pharmacogenetic testing to inform prescribing. Pharmacogenetics uses a person’s genetic data to help determine how that individual will respond to a specific medication. Although these tests can be expensive and there is some disagreement in the field about how useful they are and how often they should be ordered, several companies test an individual’s genetic profile on pharmacokinetic and pharmacodynamic measures. In psychiatry, pharmacogenetic testing is usually applied to antidepressants, with the aim of improving depression remission rates and reducing adverse effects by identifying genetic markers that could be used as clinical tools for tailoring treatment (16, 17).

The following are communication tips for psychiatrists to use when discussing biomarkers related to psychiatric disorders or treatment: