title: Effects of duloxetine treatment on brain response to painful stimulation in major depressive disorder.
abstract: Major depressive disorder (MDD) is characterized by a constellation of affective, cognitive, and somatic symptoms associated with functional abnormalities in relevant brain systems. Painful stimuli are primarily stressful and can trigger consistent responses in brain regions highly overlapping with the regions altered in MDD patients. Duloxetine has proven to be effective in treating both core emotional symptoms and somatic complaints in depression. This study aimed to assess the effects of duloxetine treatment on brain response to painful stimulation in MDD patients. A total of 13 patients and a reference group of 20 healthy subjects were assessed on three occasions (baseline, treatment week 1, and week 8) with functional magnetic resonance imaging (fMRI) during local application of painful heat stimulation. Treatment with duloxetine was associated with a significant reduction in brain responses to painful stimulation in MDD patients in regions generally showing abnormally enhanced activation at baseline. Clinical improvement was associated with pain-related activation reductions in the pregenual anterior cingulate cortex, right prefrontal cortex, and pons. Pontine changes were specifically related to clinical remission. Increased baseline activations in the right prefrontal cortex and reduced deactivations in the subgenual anterior cingulate cortex predicted treatment responders at week 8. This is the first fMRI study addressed to assess the effect of duloxetine in MDD. As a novel approach, the application of painful stimulation as a basic neural stressor proved to be effective in mapping brain response changes associated with antidepressant treatment and brain correlates of symptom improvement in regions of special relevance to MDD pathophysiology.
authors.affiliation: Institut d'Alta Tecnologia-PRBB, CRC Hospital del Mar, Faculty of Medicine, Department of Clinical Sciences, University of Barcelona, Barcelona, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: López-Solà
authors.forename: Jesus
authors.initials: J
authors.lastname: Pujol
authors.forename: Rosa
authors.initials: R
authors.lastname: Hernández-Ribas
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Harrison
authors.forename: Oren
authors.initials: O
authors.lastname: Contreras-Rodríguez
authors.forename: Carles
authors.initials: C
authors.lastname: Soriano-Mas
authors.forename: Joan
authors.initials: J
authors.lastname: Deus
authors.forename: Héctor
authors.initials: H
authors.lastname: Ortiz
authors.forename: José M
authors.initials: JM
authors.lastname: Menchón
authors.forename: Julio
authors.initials: J
authors.lastname: Vallejo
authors.forename: Narcís
authors.initials: N
authors.lastname: Cardoner
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D010147:Pain Measurement / Q000187:drug effects; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D013876:Thiophenes; D000068736:Duloxetine Hydrochloride