Abstract

It has been difficult to find robust brain structural correlates of the overall severity of major depressive disorder (MDD). We hypothesized that specific symptoms may better reveal correlates and investigated this for the severity of insomnia, both a key symptom and a modifiable major risk factor of MDD. Cortical thickness, surface area and subcortical volumes were assessed from T1-weighted brain magnetic resonance imaging (MRI) scans of 1053 MDD patients (age range 13-79 years) from 15 cohorts within the ENIGMA MDD Working Group. Insomnia severity was measured by summing the insomnia items of the Hamilton Depression Rating Scale (HDRS). Symptom specificity was evaluated with correlates of overall depression severity. Disease specificity was evaluated in two independent samples comprising 2108 healthy controls, and in 260 clinical controls with bipolar disorder. Results showed that MDD patients with more severe insomnia had a smaller cortical surface area, mostly driven by the right insula, left inferior frontal gyrus pars triangularis, left frontal pole, right superior parietal cortex, right medial orbitofrontal cortex, and right supramarginal gyrus. Associations were specific for insomnia severity, and were not found for overall depression severity. Associations were also specific to MDD; healthy controls and clinical controls showed differential insomnia severity association profiles. The findings indicate that MDD patients with more severe insomnia show smaller surfaces in several frontoparietal cortical areas. While explained variance remains small, symptom-specific associations could bring us closer to clues on underlying biological phenomena of MDD.

Details

Title
Brain structural correlates of insomnia severity in 1053 individuals with major depressive disorder: results from the ENIGMA MDD Working Group
Author
Leerssen Jeanne 1   VIAFID ORCID Logo  ; Blanken, Tessa F 1   VIAFID ORCID Logo  ; Pozzi, Elena 2 ; Jahanshad Neda 3   VIAFID ORCID Logo  ; Aftanas Lyubomir 4 ; Andreassen, Ole A 5 ; Baune, Bernhard T 6 ; Brack, Ivan 7   VIAFID ORCID Logo  ; Carballedo Angela 8 ; Ching Christopher R K 3 ; Dannlowski Udo 9 ; Dohm Katharina 9 ; Enneking Verena 9 ; Filimonova Elena 7 ; Fingas, Stella M 9 ; Frodl, Thomas 10   VIAFID ORCID Logo  ; Godlewska, Beata R 11 ; Janik, Goltermann 9 ; Gotlib, Ian H 12   VIAFID ORCID Logo  ; Grotegerd Dominik 9 ; Gruber, Oliver 13 ; Harris, Mathew A 14   VIAFID ORCID Logo  ; Hatton, Sean N 15 ; Hawkins, Emma 14 ; Hickie, Ian B 15 ; Jaworska Natalia 16   VIAFID ORCID Logo  ; Kircher Tilo 17 ; Krug Axel 18   VIAFID ORCID Logo  ; Lagopoulos, Jim 19 ; Lemke, Hannah 9 ; Li, Meng 20 ; MacMaster, Frank P 21 ; McIntosh, Andrew M 22   VIAFID ORCID Logo  ; McLellan Quinn 23   VIAFID ORCID Logo  ; Meinert, Susanne 9 ; Benson, Mwangi 24 ; Nenadić Igor 17 ; Osipov Evgeny 25   VIAFID ORCID Logo  ; Portella, Maria J 26 ; Redlich Ronny 27 ; Repple Jonathan 9 ; Sacchet, Matthew D 28 ; Sämann, Philipp G 29 ; Simulionyte Egle 13 ; Soares, Jair C 30 ; Martin, Walter 31 ; Watanabe, Norio 32 ; Whalley, Heather C 14   VIAFID ORCID Logo  ; Yüksel Dilara 33 ; Veltman, Dick J 34 ; Thompson, Paul M 3 ; Schmaal Lianne 35   VIAFID ORCID Logo  ; Van Someren Eus J W 36 

1  Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Department of Sleep and Cognition, Amsterdam, The Netherlands (GRID:grid.419918.c) (ISNI:0000 0001 2171 8263); VU University Amsterdam, Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, Amsterdam, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227) 
2  The University of Melbourne & Melbourne Health, Melbourne Neuropsychiatry Centre, Department of Psychiatry, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X); Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Australia (GRID:grid.488501.0) 
3  University of Southern California, Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Marina del Rey, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853) 
4  Scientific Research Institute of Neuroscience & Medicine, Department of Clinical Neuroscience, Behavior & Neurotechnology, Novosibirsk, Russia (GRID:grid.42505.36); Novosibirsk State University, Department of Neuroscience, Novosibirsk, Russia (GRID:grid.4605.7) (ISNI:0000000121896553) 
5  Oslo University Hospital, NORMENT Centre, Division of Mental Health and Addiction, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485); University of Oslo, Institute of Clinical Medicine, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921) 
6  University of Melbourne, Department of Psychiatry, Melbourne Medical School, Parkville, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X); University of Münster, Department of Psychiatry, Münster, Germany (GRID:grid.5949.1) (ISNI:0000 0001 2172 9288) 
7  Scientific Research Institute of Neuroscience & Medicine, Department of Clinical Neuroscience, Behavior & Neurotechnology, Novosibirsk, Russia (GRID:grid.5949.1) 
8  Trinity College Dublin, Department of Psychiatry, Dublin, Ireland (GRID:grid.8217.c) (ISNI:0000 0004 1936 9705) 
9  University of Münster, Department of Psychiatry, Münster, Germany (GRID:grid.5949.1) (ISNI:0000 0001 2172 9288) 
10  Trinity College Dublin, Department of Psychiatry, Dublin, Ireland (GRID:grid.8217.c) (ISNI:0000 0004 1936 9705); Otto von Guericke University Magdeburg, Department of Psychiatry and Psychotherapy, Magdeburg, Germany (GRID:grid.5807.a) (ISNI:0000 0001 1018 4307) 
11  University of Oxford, Psychopharmacology Research Unit, Department of Psychiatry, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
12  Stanford University, Department of Psychology, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
13  Heidelberg University, Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg, Germany (GRID:grid.7700.0) (ISNI:0000 0001 2190 4373) 
14  University of Edinburgh, Division of Psychiatry, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
15  University of Sydney, Youth Mental Health Team, Brain and Mind Centre, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
16  University of Ottawa’s Institute of Mental Health Research, Ottawa, Canada (GRID:grid.1013.3); University of Ottawa, Cellular & Molecular Medicine, Ottawa, Canada (GRID:grid.28046.38) (ISNI:0000 0001 2182 2255) 
17  Philipps-University Marburg, Department of Psychiatry and Psychotherapy, Marburg, Germany (GRID:grid.10253.35) (ISNI:0000 0004 1936 9756) 
18  Philipps-University Marburg, Department of Psychiatry and Psychotherapy, Marburg, Germany (GRID:grid.10253.35) (ISNI:0000 0004 1936 9756); University of Bonn, Department of Psychiatry and Psychotherapy, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300) 
19  Sunshine Coast Mind and Neuroscience Thompson Institute, Birtinya, Australia (GRID:grid.10388.32) 
20  Jena University Hospital, Department of Psychiatry and Psychotherapy, Jena, Germany (GRID:grid.275559.9) (ISNI:0000 0000 8517 6224); Max Planck Institute for Biological Cybernetics, Tübingen, Germany (GRID:grid.419501.8) (ISNI:0000 0001 2183 0052) 
21  University of Calgary, Psychiatry and Paediatrics, Calgary, Canada (GRID:grid.22072.35) (ISNI:0000 0004 1936 7697); Strategic Clinical Network for Addictions and Mental Health, Calgary, Canada (GRID:grid.22072.35) 
22  University of Edinburgh, Division of Psychiatry, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
23  University of Calgary, Psychiatry and Paediatrics, Calgary, Canada (GRID:grid.22072.35) (ISNI:0000 0004 1936 7697); University of Alberta, Faculty of Medicine and Dentistry, Edmonton, Canada (GRID:grid.17089.37) 
24  University of Texas Health Science Center at Houston, Department of Psychiatry, Houston, USA (GRID:grid.267308.8) (ISNI:0000 0000 9206 2401) 
25  Scientific Research Institute of Neuroscience & Medicine, Department of Clinical Neuroscience, Behavior & Neurotechnology, Novosibirsk, Russia (GRID:grid.10253.35) 
26  Institute of Biomedical Research Sant Pau, Department of Psychiatry, Barcelona, Spain (GRID:grid.10253.35); CIBERSAM, Barcelona, Spain (GRID:grid.418264.d) (ISNI:0000 0004 1762 4012) 
27  University of Münster, Department of Psychiatry, Münster, Germany (GRID:grid.5949.1) (ISNI:0000 0001 2172 9288); University of Halle, Department of Psychology, Halle, Germany (GRID:grid.9018.0) (ISNI:0000 0001 0679 2801) 
28  McLean Hospital, Harvard Medical School, Center for Depression, Anxiety, and Stress Research, Belmont, USA (GRID:grid.240206.2) (ISNI:0000 0000 8795 072X) 
29  Max Planck Institute of Psychiatry, Munich, Germany (GRID:grid.419548.5) (ISNI:0000 0000 9497 5095) 
30  University of Texas Health Science Center at Houston, UT Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, Houston, USA (GRID:grid.267308.8) (ISNI:0000 0000 9206 2401) 
31  Jena University Hospital, Department of Psychiatry and Psychotherapy, Jena, Germany (GRID:grid.275559.9) (ISNI:0000 0000 8517 6224); University of Tübingen, Department of Psychiatry and Psychotherapy, Tübingen, Germany (GRID:grid.10392.39) (ISNI:0000 0001 2190 1447) 
32  Kyoto University, Department of Health Promotion and Human Behavior, Graduate School of Public Health/ School of Public Health, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033) 
33  Philipps-University Marburg, Department of Psychiatry and Psychotherapy, Marburg, Germany (GRID:grid.10253.35) (ISNI:0000 0004 1936 9756); Center for Health Sciences, SRI International, Menlo Park, USA (GRID:grid.98913.3a) (ISNI:0000 0004 0433 0314) 
34  VU University, Department of Psychiatry, Amsterdam UMC, Amsterdam Neuroscience, Amsterdam, Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227); VU University Medical Center, Amsterdam Neuroscience, Amsterdam, Netherlands (GRID:grid.16872.3a) (ISNI:0000 0004 0435 165X) 
35  Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Australia (GRID:grid.488501.0); The University of Melbourne, Centre for Youth Mental Health, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
36  Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Department of Sleep and Cognition, Amsterdam, The Netherlands (GRID:grid.419918.c) (ISNI:0000 0001 2171 8263); VU University Amsterdam, Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, Amsterdam, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227); VU University, Department of Psychiatry, Amsterdam UMC, Amsterdam Neuroscience, Amsterdam, Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
21583188
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41398-020-01109-5
ProQuest document ID
2473291459
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.