Emma Komulainen1, Roope Heikkilä2, Lauri Nummenmaa3, Tuukka T Raij4, Catherine J Harmer5, Erkki Isometsä2, Jesper Ekelund6. 1. University of Helsinki and Helsinki University Hospital, Psychiatry, Helsinki, Finland. Electronic address: emma.komulainen@helsinki.fi. 2. University of Helsinki and Helsinki University Hospital, Psychiatry, Helsinki, Finland. 3. Turku PET Centre and Department of Psychology, University of Turku, Finland. 4. 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. 5. University Department of Psychiatry, Oxford, UK. 6. University of Turku and Turku University Hospital, Turku, Finland.
Abstract
BACKGROUND: Increased self-focus and negative self-concept play an important role in depression. Antidepressants influence self-referential processing in healthy volunteers, but their function in self-processing of depressed patients remains unknown. METHODS:Thirty-two depressed patients were randomly allocated to receive either escitalopram 10 mg or placebo for one week. After one week, neural responses to positive and negative self-referential adjectives and neutral control stimuli were assessed with functional magnetic resonance imaging. A group of matched healthy volunteers served as a control group. RESULTS: Escitalopram decreased responses of medial fronto-parietal regions to self-referential words relative to non-emotional control stimuli, driven by increased responses to the control condition. Escitalopram also increased responses in the pre-defined region of the medial prefrontal cortex (MPFC) and the anterior cingulate cortex (ACC) to positive relative to negative words. Importantly, the changes in neural responses occurred before any effect on depressive symptoms, implying a direct effect of escitalopram. Furthermore, the placebo group had decreased responses of the MPFC and the ACC to positive self-referential processing relative to the matched healthy controls. However, neural responses of the escitalopram group and the healthy unmedicated controls were similar. LIMITATIONS: Differences between the groups in self-reported depression symptoms and personality traits may have influenced the results. CONCLUSION: One-week treatment with escitalopram normalized aberrant self-referential processing in depressed patients, shifting the focus from the self to the external environment and potentiating positive self-referential processing. This may be an important factor in mechanism of action of antidepressants.
RCT Entities:
BACKGROUND: Increased self-focus and negative self-concept play an important role in depression. Antidepressants influence self-referential processing in healthy volunteers, but their function in self-processing of depressedpatients remains unknown. METHODS: Thirty-two depressedpatients were randomly allocated to receive either escitalopram 10 mg or placebo for one week. After one week, neural responses to positive and negative self-referential adjectives and neutral control stimuli were assessed with functional magnetic resonance imaging. A group of matched healthy volunteers served as a control group. RESULTS:Escitalopram decreased responses of medial fronto-parietal regions to self-referential words relative to non-emotional control stimuli, driven by increased responses to the control condition. Escitalopram also increased responses in the pre-defined region of the medial prefrontal cortex (MPFC) and the anterior cingulate cortex (ACC) to positive relative to negative words. Importantly, the changes in neural responses occurred before any effect on depressive symptoms, implying a direct effect of escitalopram. Furthermore, the placebo group had decreased responses of the MPFC and the ACC to positive self-referential processing relative to the matched healthy controls. However, neural responses of the escitalopram group and the healthy unmedicated controls were similar. LIMITATIONS: Differences between the groups in self-reported depression symptoms and personality traits may have influenced the results. CONCLUSION: One-week treatment with escitalopram normalized aberrant self-referential processing in depressedpatients, shifting the focus from the self to the external environment and potentiating positive self-referential processing. This may be an important factor in mechanism of action of antidepressants.
Authors: Manfred Klöbl; Gregor Gryglewski; Lucas Rischka; Godber Mathis Godbersen; Jakob Unterholzner; Murray Bruce Reed; Paul Michenthaler; Thomas Vanicek; Edda Winkler-Pjrek; Andreas Hahn; Siegfried Kasper; Rupert Lanzenberger Journal: Front Comput Neurosci Date: 2020-10-06 Impact factor: 2.380