From The Quarterly, Fall 2013

Using positron emission tomography (PET) scan images, researchers have identified specific brain activity that can potentially predict whether people with major depressive disorder (MDD) will best respond to an antidepressant medication or psychotherapy. This important new work offers a first step toward an evidence-based algorithm for treatment selection for depression, particularly significant since less than half of patients currently experience remission with an initial treatment.



Helen S. Mayberg, M.D., Professor of Psychiatry, Neurology and Radiology at Emory University School of Medicine, three-time NARSAD Grantee and Foundation Scientific Council member, led the study. Dr. Mayberg pioneered work using PET scans to better understand depression with her first NARSAD Young Investigator Grant in 1991, and went on to demonstrate that the subcallosal cingulate (or “Brodmann Area 25”) region of the brain is a key locus of pathology in depression. Dr. Mayberg is now well known for her innovative work in piloting deep brain stimulation (DBS) to target Area 25 to treat patients with resistant depression.



In the current study, funded by the National Institute of Mental Health and published in the June 12th issue of JAMA Psychiatry, Dr. Mayberg and her colleagues in the department of Psychiatry at Emory University including NARSAD Young Investigator Grantees Paul Holtzheimer III, M.D., and R. Cameron Craddock, Ph.D., sought to identify a biomarker (biological predictor) that could identify which type of treatment a patient would benefit from based on the individual’s brain activity. After having an initial baseline PET scan, 33 patients completed 12 weeks on escitalopram (a common antidepressant medication) and 34 patients completed 12 weeks of cognitive behavioral therapy (or CBT, a specific type of “talk therapy”). Using the pre-treatment PET scans, they compared the scan patterns in those patients as a function of their treatment type and response. They found that in the 38 patients who had clear outcomes, there was lower-than-normal activity in a brain region called the right anterior insula linked with remission after CBT and poor response to the antidepressant drug. Overactivity of the same region was linked with remission after drug treatment and poor response to CBT.  



The results of this new work are of historic importance. The data clearly suggest that treatment decisions might be based on a patient’s brain state—offering a first potential bio- marker for treatment selection—rather than evaluation of behavioral symptoms or patient and doctor preferences. More study is needed to confirm how this approach may be used and if it is relevant for other treatment options and other types of depression (beyond MDD).