Journal
MOLECULAR PSYCHIATRY
Volume 22, Issue 6, Pages 900-909Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2016.60
Keywords
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Funding
- NIH [U54 EB020403]
- Geestkracht program of the Netherlands Organisation for Health Research and Development [10-000-1002]
- VU University Medical Center
- GGZ inGeest
- Arkin
- Leiden University Medical
- Netherlands Brain Foundation [F2014(1)-24]
- Neuroscience Campus Amsterdam grant [IPB-SE-15-PSYCH]
- Australian National Health and Medical Research Council [496682, 1009064]
- US National Institute of Child Health and Human Development [RO1HD050735]
- PhD scholarship from the University of Queensland
- European Union`s Seventh Framework Programme [602450]
- Wellcome Trust [104036/Z/14/Z]
- Lundbeck and the German Research Foundation [WA 1539/4-1, SCHN 1204/3-1]
- Deutsche Forschungsgemeinschaft / German Research Association [SCHR 443/11-1]
- Exzellenz-Stiftung of the Max Planck Society
- Federal Ministry of Education and Research (BMBF) in the framework of the National Genome Research Network (NGFN) [FKZ 01GS0481]
- German Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403]
- Ministry of Cultural Affairs
- Social Ministry of the Federal State of Mecklenburg-West Pomerania
- Siemens Healthcare, Erlangen, Germany
- German Research Foundation [GR1912/5-1]
- Erasmus MC and Erasmus University Rotterdam
- Netherlands Organisation for Scientific Research (NWO)
- Netherlands Organisation for Health Research and Development (ZonMW)
- Research Institute for Diseases in the Elderly (RIDE)
- Netherlands Genomics Initiative
- Ministry of Education, Culture and Science
- Ministry of Health, Welfare and Sports
- European Commission
- Municipality of Rotterdam
- German Research Foundation (DFG) [FOR 2107, DA1151/5-1]
- Innovative Medizinische Forschung (IMF) of the Medical Faculty of Munster [DA120903, DA111107, DA211012]
- NIMH Grant [R01MH59259, R01 085667]
- National Science Foundation Integrative Graduate Education and Research Traineeship (NSF IGERT) [0801700]
- National Science Foundation Graduate Research Fellowship Program (NSF GRFP) [DGE-1147470]
- National Health and Medical Research Council of Australia (NHMRC) [1064643, 1024570]
- Dunn Foundation
- Endowed Chair in Psychiatry
- Science Foundation Ireland (SFI) Stokes Professorship Grant
- Russian Science Foundation [16-15-00128]
- National Health & Medical Research Council
- Centres of Clinical Research Excellence Grant, Austr [264611]
- [566529]
- Medical Research Council [MR/K026992/1] Funding Source: researchfish
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The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.
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