title: Neural correlates of treatment outcome in major depression.
abstract: There is a need to identify clinically useful biomarkers in major depressive disorder (MDD). In this context the functional connectivity of the orbitofrontal cortex (OFC) to other areas of the affect regulation circuit is of interest. The aim of this study was to identify neural changes during antidepressant treatment and correlates associated with the treatment outcome. In an exploratory analysis it was investigated whether functional connectivity measures moderated a response to mirtazapine and venlafaxine. Twenty-three drug-free patients with MDD were recruited from the Department of Psychiatry and Psychotherapy of the Ludwig-Maximilians University in Munich. The patients were subjected to a 4-wk randomized clinical trial with two common antidepressants, venlafaxine or mirtazapine. Functional connectivity of the OFC, derived from functional magnetic resonance imaging with an emotional face-matching task, was measured before and after the trial. Higher OFC connectivity with the left motor areas and the OFC regions prior to the trial characterized responders (p<0.05, false discovery rate). The treatment non-responders were characterized by higher OFC-cerebellum connectivity. The strength of response was positively correlated with functional coupling between left OFC and the caudate nuclei and thalami. Differences in longitudinal changes were detected between venlafaxine and mirtazapine treatment in the motor areas, cerebellum, cingulate gyrus and angular gyrus. These results indicate that OFC functional connectivity might be useful as a marker for therapy response to mirtazapine and venlafaxine and to reconstruct the differences in their mechanism of action.
authors.affiliation: Department of Psychiatry, School of Medicine & Trinity College Institute of Neuroscience, Integrated Neuroimaging, The Adelaide and Meath Hospital Incorporating the National Children's Hospital (AMiNCH), & St James's Hospital, Trinity College, Dublin, Ireland.
authors.forename: Danuta
authors.initials: D
authors.lastname: Lisiecka
authors.forename: Eva
authors.initials: E
authors.lastname: Meisenzahl
authors.forename: Johanna
authors.initials: J
authors.lastname: Scheuerecker
authors.forename: Veronica
authors.initials: V
authors.lastname: Schoepf
authors.forename: Peter
authors.initials: P
authors.lastname: Whitty
authors.forename: Aisling
authors.initials: A
authors.lastname: Chaney
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Moeller
authors.forename: Martin
authors.initials: M
authors.lastname: Wiesmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Frodl
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects*; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D002540:Cerebral Cortex / Q000503:physiopathology; D003511:Cyclohexanols / Q000008:administration & dosage / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D005145:Face; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008803:Mianserin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D009415:Nerve Net / Q000187:drug effects* / Q000503:physiopathology; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D003511:Cyclohexanols; D008803:Mianserin; D000069470:Venlafaxine Hydrochloride; D000078785:Mirtazapine