title: Multimodal functional and structural neuroimaging investigation of major depressive disorder following treatment with duloxetine.
abstract: BACKGROUND
  Longitudinal neuroimaging studies of major depressive disorder (MDD) have most commonly assessed the effects of antidepressants from the serotonin reuptake inhibitor class and usually reporting a single measure. Multimodal neuroimaging assessments were acquired from MDD patients during an acute depressive episode with serial measures during a 12-week treatment with the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine.
  
  
  METHODS
  Participants were medication-free MDD patients (n = 32; mean age 40.2 years) in an acute depressive episode and healthy controls matched for age, gender, and IQ (n = 25; mean age 38.8 years). MDD patients received treatment with duloxetine 60 mg daily for 12 weeks with an optional dose increase to 120 mg daily after 8 weeks. All participants had serial imaging at weeks 0, 1, 8, and 12 on a 3 Tesla magnetic resonance imaging (MRI) scanner. Neuroimaging tasks included emotional facial processing, negative attentional bias (emotional Stroop), resting state functional MRI and structural MRI.
  
  
  RESULTS
  A significant group by time interaction was identified in the anterior default mode network in which MDD patients showed increased connectivity with treatment, while there were no significant changes in healthy participants. In the emotional Stroop task, increased posterior cingulate activation in MDD patients normalized following treatment. No significant group by time effects were observed for happy or sad facial processing, including in amygdala responsiveness, or in regional cerebral volumes. Reduced baseline resting state connectivity within the orbitofrontal component of the default mode network was predictive of clinical response. An early increase in hippocampal volume was predictive of clinical response.
  
  
  CONCLUSIONS
  Baseline resting state functional connectivity was predictive of subsequent clinical response. Complementary effects of treatment were observed from the functional neuroimaging correlates of affective facial expressions, negative attentional bias, and resting state. No significant effects were observed in affective facial processing, while the interaction effect in negative attentional bias and individual group effects in resting state connectivity could be related to the SNRI class of antidepressant medication. The specificity of the observed effects to SNRI pharmacological treatments requires further investigation.
  
  
  BACKGROUND
  Registered at clinicaltrials.gov ( NCT01051466 ).
authors.affiliation: School of Psychology, University of East London, Arthur Edwards Building, Rm 3.11, Water Lane, London, E15 4LZ, UK. c.fu@uel.ac.uk.|Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK. c.fu@uel.ac.uk.
authors.forename: Cynthia H Y
authors.initials: CH
authors.lastname: Fu
authors.affiliation: Department of Psychiatry, University College London, London, UK. s.costafreda@ucl.ac.uk.|Department of Old Age Psychiatry, IoPPN, King's College London, London, UK. s.costafreda@ucl.ac.uk.
authors.forename: Sergi G
authors.initials: SG
authors.lastname: Costafreda
authors.affiliation: Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK. anjali.sankar@kcl.ac.uk.
authors.forename: Anjali
authors.initials: A
authors.lastname: Sankar
authors.affiliation: Psychological Services, Warneford Hospital, Oxford, UK. tracey.m.adams@gmail.com.
authors.forename: Tracey M
authors.initials: TM
authors.lastname: Adams
authors.affiliation: University of Illinois at Chicago, College of Medicine, Chicago, IL, USA. raz@uic.edu.|Jesse Brown VA Medical Center, Chicago, IL, USA. raz@uic.edu.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Rasenick
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA. liu_peng_x1@lilly.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: University of Illinois at Chicago, College of Medicine, Chicago, IL, USA. RDonati@ico.edu.|Illinois College of Optometry, Chicago, IL, USA. RDonati@ico.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Donati
authors.affiliation: Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK. luigi_maglanoc@hotmail.com.
authors.forename: Luigi A
authors.initials: LA
authors.lastname: Maglanoc
authors.affiliation: Department of Old Age Psychiatry, IoPPN, King's College London, London, UK. paul.horton@kcl.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Horton
authors.affiliation: University of Texas Health Science Center, Houston, TX, USA. Drlm@brainhealthconsultants.com.
authors.forename: Lauren B
authors.initials: LB
authors.lastname: Marangell
mesh_terms: D000328:Adult; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology*; D000068736:Duloxetine Hydrochloride; D017352:Echo-Planar Imaging; D004644:Emotions; D005149:Facial Expression; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods*; D011446:Prospective Studies; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D057190:Stroop Test; D013876:Thiophenes / Q000627:therapeutic use*
chemical_list: D000068736:Duloxetine Hydrochloride; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes