title: Limbic system white matter microstructure and long-term treatment outcome in major depressive disorder: a diffusion tensor imaging study using legacy data.
abstract: OBJECTIVE
  Treatment-resistant depression is a common clinical occurrence among patients with major depressive disorder (MDD), but its neurobiology is poorly understood. We used data collected as part of routine clinical care to study white matter integrity of the brain's limbic system and its association to treatment response.
  
  
  METHODS
  Electronic medical records of multiple large New England hospitals were screened for patients with an MDD billing diagnosis, and natural language processing was subsequently applied to find those with concurrent diffusion-weighted images, but without any diagnosed brain pathology. Treatment outcome was determined by review of clinical charts. MDD patients (n = 29 non-remitters, n = 26 partial-remitters, and n = 37 full-remitters), and healthy control subjects (n = 58) were analyzed for fractional anisotropy (FA) of the fornix and cingulum bundle.
  
  
  RESULTS
  Failure to achieve remission was associated with lower FA among MDD patients, statistically significant for the medial body of the fornix. Moreover, global and regional-selective age-related FA decline was most pronounced in patients with treatment-refractory, non-remitted depression.
  
  
  CONCLUSIONS
  These findings suggest that specific brain microstructural white matter abnormalities underlie persistent, treatment-resistant depression. They also demonstrate the feasibility of investigating white matter integrity in psychiatric populations using legacy data.
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital , Boston, MA , USA.
authors.forename: Wouter S
authors.initials: WS
authors.lastname: Hoogenboom
authors.forename: Roy H
authors.initials: RH
authors.lastname: Perlis
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Smoller
authors.forename: Qing
authors.initials: Q
authors.lastname: Zeng-Treitler
authors.forename: Vivian S
authors.initials: VS
authors.lastname: Gainer
authors.forename: Shawn N
authors.initials: SN
authors.lastname: Murphy
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Churchill
authors.forename: Isaac S
authors.initials: IS
authors.lastname: Kohane
authors.forename: Martha E
authors.initials: ME
authors.lastname: Shenton
authors.forename: Dan V
authors.initials: DV
authors.lastname: Iosifescu
mesh_terms: D000328:Adult; D016880:Anisotropy; D000928:Antidepressive Agents / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000473:pathology*; D061218:Depressive Disorder, Treatment-Resistant / Q000473:pathology*; D056324:Diffusion Tensor Imaging / Q000295:instrumentation / Q000379:methods*; D057286:Electronic Health Records / Q000706:statistics & numerical data; D005240:Feasibility Studies; D005260:Female; D020712:Fornix, Brain / Q000473:pathology; D006179:Gyrus Cinguli / Q000473:pathology; D006801:Humans; D008032:Limbic System / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009323:Natural Language Processing; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D012042:Registries; D012074:Remission Induction; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors