title: Microstructural white-matter abnormalities associated with treatment resistance, severity and duration of illness in major depression.
abstract: BACKGROUND
  Although white-matter abnormalities have been reported in middle-aged patients with major depressive disorder (MDD), few data are available on treatment-resistant MDD and the influence of relevant variables related to clinical burden of illness is far from being well established.
  
  
  METHODS
  The present study examined white-matter microstructure in a sample of 52 patients with MDD in different stages (treatment-resistant/chronic MDD, n = 18; remitted-recurrent MDD, n = 15; first-episode MDD, n = 19) and 17 healthy controls, using diffusion tensor imaging with a tract-based spatial statistics approach. Groups were comparable in age and gender distribution, and results were corrected for familywise error (FWE) rate.
  
  
  RESULTS
  Widespread significant reductions of fractional anisotropy (FA) - including the cingulum, corpus callosum, superior and inferior longitudinal fascicule - were evident in treatment-resistant/chronic MDD compared with first-episode MDD and controls (p < 0.05, FWE-corrected). Decreased FA was observed within the ventromedial prefrontal region in treatment-resistant/chronic MDD even when compared with the remitted-recurrent MDD group (p < 0.05, FWE-corrected). Longer duration of illness (β = -0.49, p = 0.04) and higher depression severity (at a trend level: β = -0.26, p = 0.06) predicted lower FA in linear multiple regression analysis at the whole-brain level. The number of previous episodes and severity of symptoms were significant predictors when focused on the ventromedial prefrontal area (β = -0.28, p = 0.04; and β = -0.29, p = 0.03, respectively). Medication effects were controlled for in the analyses and results remained unaltered.
  
  
  CONCLUSIONS
  Our findings support the notion that disruptions of white-matter microstructure, particularly in fronto-limbic networks, are associated with resistance to treatment and higher current and past burden of depression.
authors: Department of Psychiatry - Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
authors: J
authors: J
authors: de Diego-Adeliño
authors: Department of Neuroradiology - Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, Spain.
authors: P
authors: P
authors: Pires
authors: Department of Neuroradiology - Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, Spain.
authors: B
authors: B
authors: Gómez-Ansón
authors: Department of Psychiatry - Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
authors: M
authors: M
authors: Serra-Blasco
authors: Port d'Informació Científica (PIC), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors: Y
authors: Y
authors: Vives-Gilabert
authors: Department of Psychiatry - Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
authors: D
authors: D
authors: Puigdemont
authors: Department of Psychiatry - Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
authors: A
authors: A
authors: Martín-Blanco
authors: Department of Psychiatry - Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
authors: E
authors: E
authors: Alvarez
authors: Department of Psychiatry - Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
authors: V
authors: V
authors: Pérez
authors: Department of Psychiatry - Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
authors: M J
authors: MJ
authors: Portella
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D003865:Major Depressive Disorder / Q000473:pathology*; D061218:Depressive Disorder, Treatment-Resistant / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013997:Time Factors; D066127:White Matter / Q000473:pathology*