Psychiatry’s Holy Grail: New Developments in the Search for Biomarkers

The search for biomarkers certainly must be the most persistent holy grail quest in biological psychiatry. 

In the early days, the focus was on diagnostic markers. Could we find something objective that would tell us whether a person really was depressed, or whether a person was bipolar instead of schizophrenic? With the passage of time and an increase in our wisdom, most of us now see the folly of trying to find an objective chemical that would specifically link to a self-reported internal state such as depression or anxiety.

Now, as a field we are obsessed with finding biomarkers—known appropriately enough as predictive biomarkers—that predict which patient will or will not respond to any given treatment..

Although many studies have reported this and that, in my opinion the search for predictive biomarkers has been largely futile. But a recent study by my old colleagues from Emory University may represent a promising turning point in the predictive biomarker quest.

Using positron emission tomography (PET) prior to randomizing participants to 12 weeks of treatment with escitalopram or cognitive-behavioral therapy (CBT) for major depression, the researchers found that metabolic activity in the right anterior insula strongly predicted not just responding to one treatment or the other, but also not responding to one or the other treatment.

Patients with pre-treatment increased activity in the right anterior insula (when compared to activity in the rest of the brain)were much more likely to respond to escitalopram and not to respond to CBT than patients with decreased right anterior insula activity.

The predictive effect size of right anterior insula activity for discriminating between medication and psychotherapy responders was quite large, a Cohen’s d of 1.4, suggesting that if the results are replicated in larger prospective studies, this pattern of brain activity might be practically useful for determining which initial treatment a provider should select.

Needless to say, if these findings really are shown to be clinically relevant, this will be a huge advance for psychiatry, not so much because we’ll be sending all our patients off to get expensive PET scans, but because it proves the point that using biomarkers to personalize psychiatric treatment really is possible. As such, it would be the start of a new era.

Just as a personal postscript: There seems to be something more generally relevant about activity in the anterior insula. My colleagues and I recently found that increased activity in the right anterior insula in response to watching a video of other people receiving painful electric shocks strongly predicted how willing and able people were to subsequently practice compassion meditation. Interestingly, this association was specific for compassion meditation—insular activity had no predictive relevance to ability to subsequently practice a different type of meditation (in this case,mindfulness).

Do you believe that once they’re validated, predictive biomarkers such as increased right anterior insula activity will fundamentally change how we diagnose and treat our patients?

References

1. McGrath CL, Kelley ME, Holtzheimer PE, Dunlop BW, Craighead WE, Franco AR, Craddock RC, Mayberg HS. Toward a neuroimaging treatment selection biomarker for major depressive disorder. JAMA Psychiatry. 2013;70(8):821-829. 

2. Mascaro JS, Rilling JK, Negi LT, Raison CL. Pre-existing brain function predicts subsequent practice of mindfulness and compassion meditation. Neuroimage. 2013;1(69):35-42.

Charles L. Raison, MD, is an associate professor in the Department of Psychiatry, College of Medicine and the Barry and Janet Lang Associate Professor of Integrative Mental Health in the Norton School of Family and Consumer Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson, AZ. He is also the behavioral health expert for CNN.com, and he is a Psych Congress Steering Committee member.

The views expressed on this blog are solely those of the blog post author and do not necessarily reflect the views of Psych Congress Network or other Psych Congress Network authors.