title: Disruption of white matter integrity marks poor antidepressant response in bipolar disorder.
abstract: BACKGROUND
  Changes of white matter (WM) microstructure have been proposed as structural biomarkers of bipolar disorder (BD). The chronotherapeutic combination of repeated total sleep deprivation and morning light therapy (TSD+LT) can acutely reverse depressive symptoms in approximately 60% of patients, and it has been proposed as a model antidepressant treatment to investigate the neurobiological correlates of rapid antidepressant response.
  
  
  METHODS
  We tested if baseline DTI measures can predict response to treatment in 70 in-patients affected by a major depressive episode in the course of BD, treated with chronotherapeutics for one week. We performed whole-brain tract-based spatial statistics with threshold-free cluster enhancement for the DTI measures of WM microstructure integrity: fractional anisotropy, axial, radial, and mean diffusivity.
  
  
  RESULTS
  Increased mean and radial water diffusivity correlated with poor antidepressant response to TSD+LT in core WM tracts which are crucial for the functional integrity of the brain, including corpus callosum, corona radiata, cingulum bundle, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and thalamic radiation.
  
  
  CONCLUSIONS
  Limitations include issues such as generalizability, possible population stratification, medications and their effects on DTI measures, and no placebo control for chronotherapeutics. We could not consider other factors such as gene-environment interactions.
  
  
  CONCLUSIONS
  The association of increased radial and mean diffusivity with poor response to chronotherapeutic treatment warrants interest for the study of DTI measures of WM microstructure as markers for treatment response in bipolar depression.
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy; C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele, Milan, Italy; PhD Program in Philosophy and Sciences of Mind; University Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Bollettini
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy; C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Poletti
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy; C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Locatelli
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy; C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele, Milan, Italy; PhD Program in Evolutionary Psychopathology; Libera Università Maria SS. Assunta, Rome, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Vai
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy; C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Smeraldi
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Colombo
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy; C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele, Milan, Italy. Electronic address: benedetti.francesco@hsr.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Benedetti
mesh_terms: D000328:Adult; D016880:Anisotropy; D001714:Bipolar Disorder / Q000473:pathology* / Q000628:therapy*; D001921:Brain / Q000473:pathology*; D003131:Combined Modality Therapy; D003863:Depression / Q000473:pathology; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008094:Lithium / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D010789:Phototherapy; D011237:Predictive Value of Tests; D012892:Sleep Deprivation; D066127:White Matter / Q000473:pathology*
chemical_list: D008094:Lithium
keywords: Antidepressant; Biomarker; Bipolar disorder; Chronotherapeutics; Diffusion tensor imaging; White matter