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.
| Original language | English |
|---|---|
| Article number | 425 |
| Pages (from-to) | 1-11 |
| Number of pages | 11 |
| Journal | Translational Psychiatry |
| Volume | 10 |
| DOIs | |
| Publication status | Published - 8 Dec 2020 |
Funding
This project has received funding from the European Research Council (ERC) under the European Union\u2019s Horizon 2020 research and innovation program (grant agreement No. 671084 - INSOMNIA, J.L., T.F.B., E.J.W.V.S.) and from the VU University Amsterdam University Research Fellowships (J.L., T.F.B.). The ENIGMA-MDD Working Group is supported by NIH Consortium grant U54 EB020403, R01 MH116147, P41 EB015922 (P.M.T., N.J.) and R01 MH117601 (N.J., L.S.). This work was further supported by a \u201CMiguel Servet-II\u201D contract from the Spanish Ministry of Health (CP16-00020) and partly funded by PI13/01057 (M.J. P.), Wellcome Trust Grant 10436/Z/14/Z (A.M.M.), and the European Community\u2019s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 602450. This paper reflects only the author\u2019s views and the European Union is not liable for any use that may be made of the information contained therein. This work was also supported by a Wellcome Trust Strategic Award 104036/Z/14/Z and the IMAGEMEND grant (H.C.W.); Branch Out Neurological Foundation, Children\u2019s Hospital Aid Society (F.P.M.); Science Foundation Ireland (SFI) Professorship grant (T.F.); German Research Foundation (DFG, grant FOR2107 KR 3822/5-1 and KR 3822/7-2 to A.K.; DFG, grant FOR2107 KI 588/14-1 and KI 588/14-2 to T.K.; DFG, grant FOR2107 NE 2254/1-2 to I.N.; DFG, grant FOR2107 DA1151/5-1 and DA1151/5-2 to U.D.); NIMH grant R01 085667, the Dunn Foundation and the Pat Rutherford, Jr. Endowed Chair in Psychiatry (J.C.S.); German Research Foundation (SFB-TRR58, Projects C09 and Z02 to U.D.) and the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of M\u00FCnster (grant Dan3/012/17 to U.D.); Optimising Personalised Care, at scale, for Young People with Emerging Mood Disorders $951,005 over 5 years (2018-2022) (APP1136259, I.B.H.). Russian Science Foundation grant #16-15-00128 (L.A.); UK Medical Research Council, Grant number G0701421, (B.R.G.); NIMH Grants R01-MH59259 and R37-MH101495 (I.H.G.); NIA T32AG058507, NIH/NIMH 5T32MH073526, NIH grant U54EB020403 from the Big Data to Knowledge (BD2K) Program (C.R.K.C.); Wellcome Trust Strategic Award \u201CSTratifying Resilience and Depression Longitudinally\u201D (STRADL) Reference 104036/Z/14/Z (E.H.); Dr Mortimer and Theresa Sackler Foundation (M.A.H.); Innovative Medical Research (RE111604 and RE111722 to R.R.); Medical Review, Sogen-sha (N.W.); Alberta Children\u2019s Hospital Research Institute (Q.M.). MPIP data were in part provided by the Munich Antidepressant Response Signature study, supported by a grant of the Exzellenz-Stiftung of the Max Planck Society and funded by the Federal Ministry of Education and Research (BMBF) in the framework of the National Genome Research Network (NGFN), FKZ 01GS0481. Data were provided (in part) by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research and by the McDonnell Center for Systems Neuroscience at Washington University. I.B.H. has previously led community-based and pharmaceutical industry-supported (Wyeth, Eli Lily, Servier, Pfizer, AstraZeneca) projects focused on the identification and better management of anxiety and depression. He was a member of the Medical Advisory Panel for Medibank Private until October 2017, a Board Member of Psychosis Australia Trust, and a member of Veterans Mental Health Clinical Reference group. He is the Chief Scientific Advisor to, and an equity shareholder in, Innowell. Innowell has been formed by the University of Sydney and PwC to deliver the $30 m Australian Government-funded \u201CProject Synergy.\u201D Project Synergy is a 3-year program for the transformation of mental health services through the use of innovative technologies. C.R.K.C. received partial research support from Biogen, Inc. (Boston, USA) for work unrelated to the topic of this manuscript. The other authors report no financial relationships with commercial interests.
| Funders | Funder number |
|---|---|
| National Institute on Aging | T32AG058507 |
