Melissa R. Arbuckle, MD: Hi. I’m Dr. Melissa Arbuckle, vice chair for education and training in the Department of Psychiatry at Columbia University. I’m reporting on behalf of Medscape and our Columbia Psychiatry partnership. Today we’ll be discussing biomarkers with Dr. Jeffrey Lieberman. Welcome.
Jeffrey A. Lieberman, MD: Thanks, Melissa. Great to be here to talk about a subject that is near and dear to my heart.
Dr. Arbuckle: Dr. Lieberman is chair of the Department of Psychiatry at Columbia and is also director of the New York State Psychiatric Institute. Tell us about biomarkers and psychiatry, Dr Lieberman.
Dr. Lieberman: It would be nice if we had some! But first let me tell you what a biomarker is and what it would do for us. A biomarker is a biologic measure, a biologic feature, whether it’s blood pressure, pulse rate, an analyte in blood or cerebrospinal fluid, or a feature of an MRI or PET scan image of the brain that has diagnostic, prognostic, or theragnostic significance. A biomarker identifies an individual with symptoms of a specific disorder, indicates that they have this disorder, and can suggest a particular prognosis – less severe, more severe – or specify which treatment a person would likely respond to. For the entire history of our discipline, as long as physicians have studied mental illness, we have not had a diagnostic test for it. It’s a clinical diagnosis.
All illnesses in medicine began with clinical diagnosis: seizure disorder, epilepsy, was falling sickness; congestive heart failure was dropsy; for diabetes you tasted the urine to see if it was sweet or watery. But when we began to measure glucose and hemoglobin A1c, or when we developed the electrocardiogram to measure heart rhythms, and the electroencephalogram to measure brain activity, those were diagnostic tests based on biomarkers. We just don’t have them yet in psychiatry. The day we do have our first diagnostic tests, courtesy of a validated biomarker, will be a real milestone in the history of our profession.
Dr. Arbuckle: How far off might that be for psychiatry?
Dr. Lieberman: I’ve been in this profession for more than 30 years, and I’ve been saying for a while that it is coming soon. But we’re still waiting. Let me just add a cautionary note. Ever since psychiatry became scientifically minded and used scientific methodology and technology to understand the underpinnings of mental illness, there’s been an effort to identify biomarkers. It began in the 1960s with a series of false leads. There was something called the pink spot, as well as other metabolites, which were indicators on chromatographs linked to schizophrenia. This turned out to be wrong.
There was also the dexamethasone suppression test, to identify people who hypersecreted cortisol, which was believed to be diagnostic of depression. That turned out to be inadequate also.
There was the identification of genes beginning in the late 1980s. But the specific genes that indicated manic depressive illness and schizophrenia were not replicated. And now we know that the genetics of these disorders is polygenic and very complex.
So we cannot overpromise. I don’t want to say exactly when, but I will say that this is an area of intense research. There are a variety of different technologies that could yield this holy grail of diagnostic measures, including imaging measures such as MRI, PET, and nuclear medicine imaging, the use of genetics to create a polygenic risk score, and serologic analyses of blood to develop a panel of measures that may predict a specific condition or specific subtype of a condition.
It’s very likely, though, that we’ll not have a single pathognomonic test. I suspect that we’ll have several measures that, in combination, will be diagnostic or prognostic, in the same way that with cancer you have nomograms that give a prognosis. Or in the case of cardiovascular disease, where you have a lipid panel that takes into account a variety of lipid analytes to give you a risk score. I do believe that certainly within my professional lifetime, and hopefully sooner rather than later, we will see a diagnostic test.
Dr. Arbuckle: Given the different tests that did not pan out, what guidance can we offer clinicians as data come out and new potential biomarkers hit the media? How can we sift through what may or may not hold real promise?
Dr. Lieberman: I can tell practicing clinicians what not to do. Do not do what some of the charlatans in our field do. There are self-promoting psychiatrists out there who use SPECT scans to get a picture of the brain that is little more than pseudo color phrenology, and then they tell patients, “See this? This indicates that you have (this condition or that condition).” You can’t do that. Nothing we have now has that kind of validity or specificity.
However, even though a standard workup for an illness like schizophrenia does not require specific diagnostic tests, other than to rule out other conditions, imaging procedures can be useful additional information. For example, if you have an individual who presents with symptoms that meet criteria for schizophrenia and you obtain an MRI to rule out other possibilities, and the patient turns out to have dilated lateral ventricles or specific reductions in the size or distortions in the shape of certain temporal cortical structures, particularly in the hippocampus, that adds substance to your clinical diagnosis. So those kinds of things are useful. Similarly, with genetic testing, some institutions are now doing exome sequencing or whole genome sequencing that can provide a risk score. It adds something beyond a family history. These are not diagnostic, but they can add to your understanding.
Finally, with respect to schizophrenia and MRI in particular, if it does show structural abnormalities that are among the ones that have been reported for schizophrenia, this can be informative prognostically; such an individual may have a greater likelihood of having a chronic course with progression of the illness. And if that were my patient, I would be thinking that greater effort needs to be taken to ensure that the patient remains on treatment and does not suffer relapse.
Dr. Arbuckle: How do we prepare our trainees for a future of psychiatry with more biomarkers?
Dr. Lieberman: In medical school and postgraduate training, apart from understanding the method of diagnosis and the criteria for diagnoses, it’s important to understand the ancillary measures that are used in clinical medicine: blood testing, electrophysiologic measures, imaging procedures, neurocognitive testing, etc. This is a standard in terms of general medical training.
In terms of then applying it to mental illness and psychiatry, it’s a matter of knowing that these will be relevant at some point, staying apprised of the research literature that is generating data that pertain to the use of these measures for diagnostic, prognostic, or treatment-specific purposes, and then gauging how useful these will be. Right now, these measures are not required for diagnosis. They’re not validated sufficiently so that third-party payers will uniformly reimburse for them, but at some point they will be. Even before that time occurs, there are some measures that can be informative and enhance confidence in the diagnosis or add information about treatment response and outcome.
Dr. Arbuckle: We’re hearing about biotypes and how biotypes may not map to our current diagnostic systems. What are your thoughts about that?
Dr. Lieberman: You know, psychiatry has always been kind of the stepchild of medicine. And related to that, the Diagnostic and Statistical Manual of Mental Disorders (DSM) is the punching bag of the critics of psychiatry and the purported reason it hasn’t progressed faster. Sitting here at Columbia, the home of Robert Spitzer, who was the pioneer of the modern method of nosology that we still use in the DSM, it’s disappointing that we continue to lob tomatoes at this system, which is the best. It took psychiatry out of what was a dark age of clinical methodology and put it on solid scientific footing. That was in the late 1970s with [the development of] DSM-III.
And as much as we would like to have further progress, which would allow for not using a list of criteria in a menu-driven fashion to establish diagnoses, we’d like to have it be like a glucose tolerance test or an angiogram.
We’d like to do that, but we can’t yet. So there’s this aspirational desire to have something better, and this is permeating and motivating a lot of the research, which is good. But to claim that these don’t map to the current DSM and therefore invalidate the DSM-defined diagnoses is wrong and self-defeating. So if they don’t map to the current DSM diagnosis, is the diagnosis wrong or are the biotypes wrong? I believe it’s wishful thinking; individuals are trying to project their desires onto clinical practice, and it’s not desirable to do that. If there was anything that was an improvement on the DSM, it would have been incorporated into our practice.
The question about the limitations of DSM and the improved methods of neuroscientifically informed diagnostic systems was an issue that brought me into a confrontation with our former director of the National Institute of Mental Health (NIMH) in 2013.
After 5 years of the DSM task force laboring to revise the fifth edition of the DSM, as it was about to be launched, our former director, Tom Insel, disavowed it and proposed as a preferable alternative the research domains criteria (RDoC) system that was in development at the NIMH, which I believe epitomized this kind of sour grapes at what psychiatry didn’t have – an aspiration to have a more neuroscientifically informed diagnostic system. And as soon as he made the statement publicly, he had to walk it back because the RDoC system or any other system was not ready for prime time. It would have been a catastrophe if it would have been the one that informed clinical psychiatry. There was nothing that was superior to the DSM to be used at the time. This shows how frustration sometimes impels people to make rash statements.
We’re on the right track. Our field is progressing enormously, and one has to remember that everything that’s relevant in terms of being scientifically based and validated through empirical research in clinical psychiatry and mental illness has happened since the last half of the 20th century.
It is a very short period of time. We’ve made tremendous progress, and we’re continuing to make progress toward the milestone we’re all hoping for, where we have diagnostic tests. But we shouldn’t shortchange ourselves or underestimate the progress we have made in the meantime.
Dr. Arbuckle: This has been a great conversation. Signing off for Medscape and Columbia Psychiatry. Thank you.
Dr. Lieberman is chairman of the Department of Psychiatry at Columbia University. He is a former president of the American Psychiatric Association. Dr. Arbuckle is vice chair for education and director of resident education in the Department of Psychiatry at Columbia University. She is particularly interested in the role of medical education in translating research into the practice of psychiatry.
This article first appeared on Medscape.com.