title: Single dose of mirtazapine modulates whole-brain functional connectivity during emotional narrative processing.
abstract: The link between neurotransmitter-level effects of antidepressants and their clinical effect remain poorly understood. A single dose of mirtazapine decreases limbic responses to fearful faces in healthy subjects, but it is unknown whether this effect applies to complex emotional situations and dynamic connectivity between brain regions. Thirty healthy volunteers listened to spoken emotional narratives during functional magnetic resonance imaging (fMRI). In an open-label design, 15 subjects received 15mg of mirtazapine two hours prior to fMRI while 15 subjects served as a control group. We assessed the effects of mirtazapine on regional neural responses and dynamic functional connectivity associated with valence and arousal. Mirtazapine attenuated responses to unpleasant events in the right fronto-insular cortex, while modulating responses to arousing events in the core limbic regions and the cortical midline structures (CMS). Mirtazapine decreased responses to unpleasant and arousing events in sensorimotor areas and the anterior CMS implicated in self-referential processing and formation of subjective feelings. Mirtazapine increased functional connectivity associated with positive valence in the CMS and limbic regions. Mirtazapine triggers large-scale changes in regional responses and functional connectivity during naturalistic, emotional stimuli. These span limbic, sensorimotor, and midline brain structures, and may be relevant to the clinical effectiveness of mirtazapine.
authors.affiliation: University of Helsinki and Helsinki University Hospital, Psychiatry, Helsinki, Finland. Electronic address: emma.komulainen@helsinki.fi.
authors.forename: Emma
authors.initials: E
authors.lastname: Komulainen
authors.affiliation: Aalto University, School of Science, Department of Neuroscience and Biomedical Engineering, Espoo, Finland.
authors.forename: Enrico
authors.initials: E
authors.lastname: Glerean
authors.affiliation: University of Helsinki and Helsinki University Hospital, Psychiatry, Helsinki, Finland.
authors.forename: Katarina
authors.initials: K
authors.lastname: Meskanen
authors.affiliation: University of Helsinki and Helsinki University Hospital, Psychiatry, Helsinki, Finland.
authors.forename: Roope
authors.initials: R
authors.lastname: Heikkilä
authors.affiliation: Turku PET Centre and Department of Psychology, University of Turku, Turku, Finland.
authors.forename: Lauri
authors.initials: L
authors.lastname: Nummenmaa
authors.affiliation: University of Helsinki and Helsinki University Hospital, Psychiatry, Helsinki, Finland; Aalto University, School of Science, Department of Neuroscience and Biomedical Engineering, Espoo, Finland; Aalto NeuroImaging, Aalto University, Espoo, Finland.
authors.forename: Tuukka T
authors.initials: TT
authors.lastname: Raij
authors.affiliation: University of Helsinki, Institute of Behavioral Sciences, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland; Helsinki collegium of Advanced Studies, University of Helsinki, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Lahti
authors.affiliation: University of Helsinki and Helsinki University Hospital, Psychiatry, Helsinki, Finland; National Institute of Health and Welfare, Department of Mental Health and Substance Abuse Services, Helsinki, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Jylhä
authors.affiliation: University of Helsinki and Helsinki University Hospital, Psychiatry, Helsinki, Finland.
authors.forename: Tarja
authors.initials: T
authors.lastname: Melartin
authors.affiliation: University of Helsinki and Helsinki University Hospital, Psychiatry, Helsinki, Finland.
authors.forename: Erkki
authors.initials: E
authors.lastname: Isometsä
authors.affiliation: University of Helsinki and Helsinki University Hospital, Psychiatry, Helsinki, Finland; Vaasa Hospital District, Department of Psychiatry, Vaasa, Finland.
authors.forename: Jesper
authors.initials: J
authors.lastname: Ekelund
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage; D000328:Adult; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D001931:Brain Mapping / Q000379:methods; D004644:Emotions / Q000187:drug effects* / Q000502:physiology; D005239:Fear / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008803:Mianserin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000078785:Mirtazapine; D033262:Narration; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D000317:Adrenergic alpha-Antagonists; D008803:Mianserin; D000078785:Mirtazapine
keywords: Antidepressant; Emotion; Information processing; Neural network; fMRI