title: Co-Variation of Peripheral Levels of miR-1202 and Brain Activity and Connectivity During Antidepressant Treatment.
abstract: MicroRNAs are short non-coding molecules that play a major role in regulating gene expression. Peripheral levels of miR-1202 have been shown to predict and mediate antidepressant response. However, it is not clear to what extent these peripheral measures reflect central neural changes in vivo. We approached this problem with the combined use of peripheral miR-1202 measures and neuroimaging. At baseline and after 8 weeks of desvenlafaxine (50-100 mg die), 20 patients were scanned with 3T magnetic resonance imaging, first at rest then during the Go/NoGo task, a classical test of response inhibition. Blood samples were collected at both time points. During resting state, lower baseline miR-1202 levels were predictive of increased connectivity from T0 to T8 between the posterior cingulate and the prefrontal, parietal, and occipital cortices. Changes in miR-1202 levels following desvenlafaxine treatment were negatively correlated with changes in activity in right precuneus within the default-mode network, and in connectivity between the posterior cingulate and the temporal and prefrontal cortices, and the precuneus. During the Go/NoGo task, baseline miR-1202 levels and changes in these levels were correlated with activity changes in different regions, including bilateral prefrontal, insular, cingulate, and temporal cortices, and left putamen and claustrum. Finally, secondary analyses in a subset of patients showed a trend for a significant correlation between miR-1202 levels and glutamate levels measured by spectroscopy. Changes in peripheral miR-1202 levels were therefore associated with changes in brain activity and connectivity in a network of brain regions associated with depression and antidepressant response. These effects may be mediated by the glutamatergic system.
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute, Montréal, Québec, Canada.|Max Planck Institute of Psychiatry, Department of Stress Neurobiology and Neurogenetics, Munich, Germany.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Lopez
authors.affiliation: Department of Radiology, Nîmes Academic Hospital, Nîmes, France &EA 2415, Montpellier University, Montpellier, France.
authors.forename: Fabricio
authors.identifier: http://orcid.org/0000-0003-3317-8756
authors.initials: F
authors.lastname: Pereira
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute, Montréal, Québec, Canada.|Department of Psychiatry, McGill University, Montréal,, Québec, Canada.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Richard-Devantoy
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute, Montréal, Québec, Canada.|Department of Psychiatry, McGill University, Montréal,, Québec, Canada.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Berlim
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute, Montréal, Québec, Canada.|Department of Psychiatry, McGill University, Montréal,, Québec, Canada.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Chachamovich
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute, Montréal, Québec, Canada.|Department of Psychiatry, McGill University, Montréal,, Québec, Canada.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Fiori
authors.affiliation: Laboratory of Pharmacogenomics, Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Niola
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute, Montréal, Québec, Canada.|Department of Psychiatry, McGill University, Montréal,, Québec, Canada.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute, Montréal, Québec, Canada.|Department of Psychiatry, McGill University, Montréal,, Québec, Canada.|Department of Psychiatry, Nîmes Academic Hospital, Nîmes, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Jollant
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D001931:Brain Mapping; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D000069468:Desvenlafaxine Succinate / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D009483:Neuropsychological Tests; D012146:Rest; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; C000591596:MIRN1202 microRNA, human; D035683:MicroRNAs; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; D000069468:Desvenlafaxine Succinate