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Intrinsic Patterns of Functional Brain Connectivity in MDD

Functional connectivity patterns of brain regions between and within networks may play an important role in identifying a favorable response for a drug treatment for major depressive disorder (MDD), according to a new study. Participants in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study underwent structural and resting-state functional MRI at baseline. They were then randomly assigned to received either sertraline or placebo treatment for 8 weeks (n=279). Researchers found:

  • Prediction of response to sertraline involved several within- and between-network connectivity patterns.
  • Higher connectivity within the default mode network predicted better outcomes specifically for sertraline, as did greater between-network connectivity of the default mode and executive control networks.
  • Both placebo and sertraline outcomes were predicted by between-network hippocampal connectivity.


Fatt CRC, et al. Effect of intrinsic patterns of functional brain connectivity in moderating antidepressant treatment response in major depression. [Published online ahead of print September 20, 2019]. Psychiatry. doi: 10.1176/appi.ajp.2019.18070870.


Earlier studies have shown that brain imaging can predict patients that will respond to either an SSRI or cognitive-behavioral therapy (CBT). In one such PET imaging study, investigators found that insular cortex hypometabolism allowed greater remission with CBT, while hypermetabolism allowed more SSRI remissions (JAMA Psychiatry. 2013;70(8):821-829). In an fMRI study, positive summed connectivity allowed for CBT-induced remission, while negative summed connectivity led to SSRI-induced remission (Am J Psychiatry. 2017;174:533-545). In the current study, investigators again found that brain imaging may help predict which treatment will be most effective. Higher network connectivity predicted SSRI response versus failure. Interestingly, non-response and placebo response were attributed to lesser connectivity and differing neurocircuitry. As we gain additional functional imaging findings, we may be able to better predict which patients will respond to medication versus psychotherapy, and, possibly, patients that will have greater placebo induced remission. This latter finding may be especially beneficial for choosing from a list of medications with varying risks for side effects. For example, if we know placebo response is likely to be high, then we would want to use a medication that carries less risk.—Thomas L. Schwartz, MD; Senior Associate Dean of Education, Interim Chair/Professor of Psychiatry, SUNY Upstate Medical University.