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Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group.

ABSTRACT: The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.

SUBMITTER: Kelly S

PROVIDER: S-EPMC5984078 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group.

Kelly S S Jahanshad N N Zalesky A A Kochunov P P Agartz I I Alloza C C Andreassen O A OA Arango C C Banaj N N Bouix S S Bousman C A CA Brouwer R M RM Bruggemann J J Bustillo J J Cahn W W Calhoun V V Cannon D D Carr V V Catts S S Chen J J Chen J-X JX Chen X X Chiapponi C C Cho Kl K KK Ciullo V V Corvin A S AS Crespo-Facorro B B Cropley V V De Rossi P P Diaz-Caneja C M CM Dickie E W EW Ehrlich S S Fan F-M FM Faskowitz J J Fatouros-Bergman H H Flyckt L L Ford J M JM Fouche J-P JP Fukunaga M M Gill M M Glahn D C DC Gollub R R Goudzwaard E D ED Guo H H Gur R E RE Gur R C RC Gurholt T P TP Hashimoto R R Hatton S N SN Henskens F A FA Hibar D P DP Hickie I B IB Hong L E LE Horacek J J Howells F M FM Hulshoff Pol H E HE Hyde C L CL Isaev D D Jablensky A A Jansen P R PR Janssen J J Jönsson E G EG Jung L A LA Kahn R S RS Kikinis Z Z Liu K K Klauser P P Knöchel C C Kubicki M M Lagopoulos J J Langen C C Lawrie S S Lenroot R K RK Lim K O KO Lopez-Jaramillo C C Lyall A A Magnotta V V Mandl R C W RCW Mathalon D H DH McCarley R W RW McCarthy-Jones S S McDonald C C McEwen S S McIntosh A A Melicher T T Mesholam-Gately R I RI Michie P T PT Mowry B B Mueller B A BA Newell D T DT O'Donnell P P Oertel-Knöchel V V Oestreich L L Paciga S A SA Pantelis C C Pasternak O O Pearlson G G Pellicano G R GR Pereira A A Pineda Zapata J J Piras F F Potkin S G SG Preda A A Rasser P E PE Roalf D R DR Roiz R R Roos A A Rotenberg D D Satterthwaite T D TD Savadjiev P P Schall U U Scott R J RJ Seal M L ML Seidman L J LJ Shannon Weickert C C Whelan C D CD Shenton M E ME Kwon J S JS Spalletta G G Spaniel F F Sprooten E E Stäblein M M Stein D J DJ Sundram S S Tan Y Y Tan S S Tang S S Temmingh H S HS Westlye L T LT Tønnesen S S Tordesillas-Gutierrez D D Doan N T NT Vaidya J J van Haren N E M NEM Vargas C D CD Vecchio D D Velakoulis D D Voineskos A A Voyvodic J Q JQ Wang Z Z Wan P P Wei D D Weickert T W TW Whalley H H White T T Whitford T J TJ Wojcik J D JD Xiang H H Xie Z Z Yamamori H H Yang F F Yao N N Zhang G G Zhao J J van Erp T G M TGM Turner J J Thompson P M PM Donohoe G G

Molecular psychiatry 20171017 5

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the p ...[more]

PMID: 29038599

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Project description:Diffusion tensor imaging (DTI) is a noninvasive, quantitative MRI technique that measures white matter (WM) integrity. Many brain dimensions are heritable, including white matter integrity measured with DTI. Family studies are valuable to provide insights into the interactive effects of non-environmental factors on multiple sclerosis (MS). To examine the contribution of familial factors to the diffusion signals across WM microstructure, we performed DTI and calculated neurite orientation dispersion plus density imaging (NODDI) diffusion parameters in two patient groups comprising familial and sporadic forms of multiple sclerosis and their unaffected relatives. We divided 111 subjects (49 men and 62 women: age range 19-60) into three groups conforming to their MS history. The familial MS group included 30 participants (patients; n = 16, healthy relatives; n = 14). The sporadic group included 41 participants (patients; n = 10, healthy relatives; n = 31). Forty age-matched subjects with no history of MS in their families were defined as the control group. To study white matter integrity, two methods were employed: one for calculating the mean of DTI, FA, and MD parameters on 18 tracts using Tracts Constrained by Underlying Anatomy (TRACULA) and the other for whole brain voxel-based analysis using tract-based spatial statistics (TBSS) on NDI and ODI parameters derived from NODDI and DTI parameters. Voxel-based analysis showed considerable changes in FA, MD, NDI, and ODI in the familial group when compared with the control group, reflecting widespread impairment of white matter in this group. The analysis of 18 tracts with TRACULA revealed increased MD and FA reduction in more tracts (left and right ILF, UNC, and SLFT, forceps major and minor) in familial MS patients vs. the control group. There were no significant differences between the patient groups. We found no consequential changes in healthy relatives of both patient groups in voxel-based and tract analyses. Considering the multifactorial etiology of MS, familial studies are of great importance to clarify the effects of certain predisposing factors on demyelinating brain pathology.

Dataset Information

Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group.

Publications

Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group.

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