title: Resting state functional connectivity and treatment response in late-life depression.
abstract: Indices of functional connectivity in the default mode network (DMN) are promising neural markers of treatment response in late-life depression. We examined the differences in DMN functional connectivity between treatment-responsive and treatment-resistant depressed older adults. Forty-seven depressed older adults underwent MRI scanning pre- and post-pharmacotherapy. Forty-six never depressed older adults underwent MR scanning as comparison subjects. Treatment response was defined as achieving a Hamilton Depression Rating Scale of 10 or less post-treatment. We analyzed resting state functional connectivity using the posterior cingulate cortex as the seed region-of-interest. The resulting correlation maps were employed to investigate between-group differences. Additionally we examined the association between white matter hyperintensity burden and functional connectivity results. Comparison of pre- and post-treatment scans of depressed participants revealed greater post-treatment functional connectivity in the frontal precentral gyrus. Relative to treatment-responsive participants, treatment-resistant participants had increased functional connectivity in the left striatum. When adjusting for white matter hyperintensity burden, the observed differences lost significance for the PCC-prefrontal functional connectivity, but not for the PCC-striatum functional connectivity. The post-treatment "frontalization" of the DMN connectivity suggests a normalizing effect of antidepressant treatment. Moreover, our study confirms the central role of white matter lesions in disrupting brain functional connectivity.
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: andrcx@upmc.edu.
authors.forename: Carmen
authors.initials: C
authors.lastname: Andreescu
authors.forename: Dana L
authors.initials: DL
authors.lastname: Tudorascu
authors.forename: Meryl A
authors.initials: MA
authors.lastname: Butters
authors.forename: Erica
authors.initials: E
authors.lastname: Tamburo
authors.forename: Meenal
authors.initials: M
authors.lastname: Patel
authors.forename: Julie
authors.initials: J
authors.lastname: Price
authors.forename: Jordan F
authors.initials: JF
authors.lastname: Karp
authors.forename: Charles F
authors.initials: CF
authors.lastname: Reynolds
authors.forename: Howard
authors.initials: H
authors.lastname: Aizenstein
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017072:Neostriatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D012146:Rest; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents
keywords: Default Mode Network; Late-life depression; MRI; Treatment response; White matter hyperintensity