Limbic system white matter microstructure and long-term treatment outcome in major depressive disorder: a diffusion tensor imaging study using legacy data

World J Biol Psychiatry. 2014 Feb;15(2):122-34. doi: 10.3109/15622975.2012.669499. Epub 2012 Apr 30.


Objectives: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anisotropy
  • Antidepressive Agents / therapeutic use
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / pathology*
  • Depressive Disorder, Treatment-Resistant / pathology*
  • Diffusion Tensor Imaging / instrumentation
  • Diffusion Tensor Imaging / methods*
  • Electronic Health Records / statistics & numerical data
  • Feasibility Studies
  • Female
  • Fornix, Brain / pathology
  • Gyrus Cinguli / pathology
  • Humans
  • Limbic System / pathology*
  • Male
  • Middle Aged
  • Natural Language Processing
  • Nerve Fibers, Myelinated / pathology
  • Registries*
  • Remission Induction
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Time Factors
  • Treatment Outcome


  • Antidepressive Agents
  • Serotonin Uptake Inhibitors