Brain structural correlates of insomnia severity in 1053 individuals with major depressive disorder: results from the ENIGMA MDD Working Group

Jeanne Leerssen*, Tessa F. Blanken, Elena Pozzi, Neda Jahanshad, Lyubomir Aftanas, Ole A. Andreassen, Bernhard T. Baune, Ivan Brack, Angela Carballedo, Christopher R. K. Ching, Udo Dannlowski, Katharina Dohm, Verena Enneking, Elena Filimonova, Stella M. Fingas, Thomas Frodl, Beata R. Godlewska, Janik Goltermann, Ian H. Gotlib, Dominik GrotegerdOliver Gruber, Mathew A. Harris, Sean N. Hatton, Emma Hawkins, Ian B. Hickie, Natalia Jaworska, Tilo Kircher, Axel Krug, Jim Lagopoulos, Hannah Lemke, Meng Li, Frank P. MacMaster, Andrew M. McIntosh, Quinn McLellan, Susanne Meinert, Benson Mwangi, Igor Nenadić, Evgeny Osipov, Maria J. Portella, Ronny Redlich, Jonathan Repple, Matthew D. Sacchet, Philipp G. Sämann, Egle Simulionyte, Jair C. Soares, Martin Walter, Norio Watanabe, Heather C. Whalley, Dilara Yüksel, Dick J. Veltman, Paul M. Thompson, Lianne Schmaal, Eus J. W. van Someren

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Article number425
JournalTranslational psychiatry
Issue number1
Publication statusPublished - 1 Dec 2020

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