title: Salience Network Functional Connectivity Predicts Placebo Effects in Major Depression.
abstract: BACKGROUND
  Recent neuroimaging studies have demonstrated resting-state functional connectivity (rsFC) abnormalities among intrinsic brain networks in Major Depressive Disorder (MDD); however, their role as predictors of treatment response has not yet been explored. Here, we investigate whether network-based rsFC predicts antidepressant and placebo effects in MDD.
  
  
  METHODS
  We performed a randomized controlled trial of two weeklong, identical placebos (described as having either "active" fast-acting, antidepressant effects or as "inactive") followed by a ten-week open-label antidepressant medication treatment. Twenty-nine participants underwent a rsFC fMRI scan at the completion of each placebo condition. Networks were isolated from resting-state blood-oxygen-level-dependent signal fluctuations using independent component analysis. Baseline and placebo-induced changes in rsFC within the default-mode, salience, and executive networks were examined for associations with placebo and antidepressant treatment response.
  
  
  RESULTS
  Increased baseline rsFC in the rostral anterior cingulate (rACC) within the salience network, a region classically implicated in the formation of placebo analgesia and the prediction of treatment response in MDD, was associated with greater response to one week of active placebo and ten weeks of antidepressant treatment. Machine learning further demonstrated that increased salience network rsFC, mainly within the rACC, significantly predicts individual responses to placebo administration.
  
  
  CONCLUSIONS
  These data demonstrate that baseline rsFC within the salience network is linked to clinical placebo responses. This information could be employed to identify patients who would benefit from lower doses of antidepressant medication or non-pharmacological approaches, or to develop biomarkers of placebo effects in clinical trials.
authors.affiliation: Molecular and Behavioral Neuroscience Institute and Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Sikora
authors.affiliation: Molecular and Behavioral Neuroscience Institute and Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Heffernan
authors.affiliation: Molecular and Behavioral Neuroscience Institute and Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Erich T
authors.initials: ET
authors.lastname: Avery
authors.affiliation: Molecular and Behavioral Neuroscience Institute and Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Mickey
authors.affiliation: Molecular and Behavioral Neuroscience Institute and Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA ; Department of Radiology, Medical School, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Jon-Kar
authors.initials: JK
authors.lastname: Zubieta
authors.affiliation: Molecular and Behavioral Neuroscience Institute and Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Peciña
keywords: Major Depression; biomarkers of treatment response; large-scale connectivity networks; placebo effects; resting-state functional connectivity