title: Magnetic Resonance Imaging Measures of Brain Structure to Predict Antidepressant Treatment Outcome in Major Depressive Disorder.
abstract: BACKGROUND
  Less than 50% of patients with Major Depressive Disorder (MDD) reach symptomatic remission with their initial antidepressant medication (ADM). There are currently no objective measures with which to reliably predict which individuals will achieve remission to ADMs.
  
  
  METHODS
  157 participants with MDD from the International Study to Predict Optimized Treatment in Depression (iSPOT-D) underwent baseline MRIs and completed eight weeks of treatment with escitalopram, sertraline or venlafaxine-ER. A score at week 8 of 7 or less on the 17 item Hamilton Rating Scale for Depression defined remission. Receiver Operator Characteristics (ROC) analysis using the first 50% participants was performed to define decision trees of baseline MRI volumetric and connectivity (fractional anisotropy) measures that differentiated non-remitters from remitters with maximal sensitivity and specificity. These decision trees were tested for replication in the remaining participants.
  
  
  RESULTS
  Overall, 35% of all participants achieved remission. ROC analyses identified two decision trees that predicted a high probability of non-remission and that were replicated: 1. Left middle frontal volume < 14 · 8 mL & right angular gyrus volume > 6 · 3 mL identified 55% of non-remitters with 85% accuracy; and 2. Fractional anisotropy values in the left cingulum bundle < 0 · 63, right superior fronto-occipital fasciculus < 0 · 54 and right superior longitudinal fasciculus < 0 · 50 identified 15% of the non-remitters with 84% accuracy. All participants who met criteria for both decision trees were correctly identified as non-remitters.
  
  
  CONCLUSIONS
  Pretreatment MRI measures seem to reliably identify a subset of patients who do not remit with a first step medication that includes one of these commonly used medications. Findings are consistent with a neuroanatomical basis for non-remission in depressed patients.
  
  
  BACKGROUND
  Brain Resource Ltd is the sponsor for the iSPOT-D study (NCT00693849).
authors.affiliation: The Brain Dynamics Centre, Westmead Millennium Institute, Sydney Medical School, Sydney, NSW, Australia ; Discipline of Psychiatry, Sydney Medical School, The University of Sydney, Westmead Hospital, Sydney, NSW, Australia.
authors.forename: Mayuresh S
authors.initials: MS
authors.lastname: Korgaonkar
authors.affiliation: Brain Resource Ltd, Sydney, NSW, Australia ; Brain Resource Ltd, San Francisco, CA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Rekshan
authors.affiliation: The Brain Dynamics Centre, Westmead Millennium Institute, Sydney Medical School, Sydney, NSW, Australia ; Brain Resource Ltd, Sydney, NSW, Australia ; Brain Resource Ltd, San Francisco, CA, USA.
authors.forename: Evian
authors.initials: E
authors.lastname: Gordon
authors.affiliation: Duke-National University of Singapore, Singapore.
authors.forename: A John
authors.initials: AJ
authors.lastname: Rush
authors.affiliation: The Brain Dynamics Centre, Westmead Millennium Institute, Sydney Medical School, Sydney, NSW, Australia ; Department of Psychiatry and Behavioral Sciences, Stanford University, 401 Quarry Road, Stanford, CA 94305, USA ; Sierra-Pacific Mental Illness Research, Education, Clinical Center (MIRECC), Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA.
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Williams
authors.affiliation: PGSP-Stanford University Consortium, Palo Alto, CA, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Blasey
authors.affiliation: The Brain Dynamics Centre, Westmead Millennium Institute, Sydney Medical School, Sydney, NSW, Australia ; Sydney Translational Imaging Laboratory, Charles Perkins Centre and Sydney Medical School, University of Sydney, NSW 2006, Australia ; Department of Radiology, Royal Prince Alfred Hospital, Camperdown, Sydney, NSW 2006, Australia.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Grieve
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology*; D015331:Cohort Studies; D003663:Decision Trees; D003710:Demography; D003865:Major Depressive Disorder / Q000188:drug therapy*; D056324:Diffusion Tensor Imaging; D005260:Female; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D012074:Remission Induction; D015203:Reproducibility of Results; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents
keywords: Biomarker predictors; Decision trees; Diffusion tensor imaging; Magnetic resonance imaging; Major depressive disorder; Remission; Replication; iSPOT-D