Đang tải... (xem toàn văn)
Objectives: Brain structure changes in schizophrenia (SZ) have been a focus for recent decades. Yet such researches, especially those on gray and white matters in Vietnamese SZ patients, still parsimonious. The present study concerned changes of brain structures including gray and white matters in SZ.
TẠP CHÍ Y - DƢỢC HỌC QUÂN SỰ SỐ CHUYÊN ĐỀ HÌNH THÁI HỌC-2017 GRAY AND WHITE MATTER REDUCTION IN SCHIZOPHRENIA PATIENTS Dang Tien Truong*; Nguyen Duy Bac*; Tran Ngoc Anh*; Tran Hai Anh* SUMMARY Objectives: Brain structure changes in schizophrenia (SZ) have been a focus for recent decades Yet such researches, especially those on gray and white matters in Vietnamese SZ patients, still parsimonious The present study concerned changes of brain structures including gray and white matters in SZ Subjects and methods: Participants included 39 patients with SZ and 40 healthy control individuals, they were underwent 1.5 tesla MRI Automated segmentation of brain structures was performed using FreeSurfer software Results: There was a significant reduction in total brain with ventricles, total brain with ventricles/ICV ratio, total brain without ventricles, and gray and white matters in SZ patients, but an enlargement of ventricles comparing to those in controls Conclusion: Our results of MRI study in Vietnamese people support a notion of the reduction of gray and white matters and of brain volume in SZ * Keywords: Schizophrenia; MRI; Brain structure INTRODUCTION Schizophrenia is a mental disorder with variations in symptoms and pathophysiology, but its etiology still remains largely unclear [1] The disease is characterized by alterations in cognition, motivation, memory, and social communications Research interest in investigating brain abnormalities in SZ thus paled until 1976, when the first computed tomography showed enlarged lateral ventricles in SZ and magnetic resonance imaging (MRI) studies followed [12] MRI has been a powerful tool for visualizing soft tissue contrast in the brain and no known adverse effects Hence, there have been a plentiful number of studies using MRI with higher resolution [2, 3], which report morphologic abnormalities of the brain in SZ [5, 7], the correlation of symptoms and brain changes [5, 6, 11], and between cognitive functions with gray matter (GM) [9, 10] and white matter (WM) [6, 12] In Vietnam, most among numerous studies on SZ have concentrated on its epidemiological and/or clinical aspects, and still few those concerned its pathology (such as serotonin level in SZ patients) or brain morphology in SZ, but no studies reported for GM and WM This report showed findings on volumes of the whole brain/cranium and regions generally, and GM and WM in SZ specifically SUBJECTS AND METHODS Subjects 39 schizophrenic patients and 40 healthy controls were recruited in the research, they were all right-handed SZ cases were collected from Department of Psychiatry,103 Hospital, Vietnam Military Medical University * Vietnam Military Medical University Corresponding author: Tran Hai Anh (anhhtr@yahoo.com) Date received: 30/07/2017 Date accepted: 09/09/2017 656 TẠP CHÍ Y - DƢỢC HỌC QUÂN SỰ SỐ CHUYÊN ĐỀ HÌNH THÁI HỌC-2017 The SZ patients were diagnosed by criteria of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), confirming by two independent psychiatrists All patients had no second psychiatric condition All healthy controls had no history of psychiatric disorder, current psychiatric disorder, neurological or other significant medical disorders potentially influencing neurocognitive function, and first-degree relatives with psychiatric disorders according to DSM-IV automated transformation, segmentation of the subcortical WM and deep GM, volumetric structures intensity normalization, tessellation of the GM and WM boundary, automated topology correction, and surface deformation following intensity gradients to optimally place the gray/white and gray/cerebrospinal fluid borders at the location where the greatest shift in intensity defines the transition to the other tissues Once the cortical models were completed, Methods Talairach a number of deformable procedures can be performed for further * MRI acquisition: data processing and analyzing including The MRI scans were acquired on a 1.5T system, using a three-dimensional spoiled gradient echo sequence according to the following protocol: mm sagittal slices with TR = 15 ms, TE = ms, Flip angle = 30°, FOV = 256, Matrix = 256 x 256 Scans were inspected for motion artifacts and a neuroradiologist confirmed absence of gross pathological findings * MRI scan processing and calculation of morphological brain: surface inflation, registration to a spherical atlas which is based on individual cortical folding patterns to match cortical geometry across subjects [3], parcellation of the cerebral cortex into units with respect to gyral and sulcal structure [3, 4], and creation of a variety of surface based data including maps of curvature and sulcal depth * Statistical analysis: We used FreeSurfer software package Volumes of brain regions were calculated (version 5.3.0, http://surfer.nmr.mgh.harvard.edu) and compared using a student t-test for processing images The technical The volumes were compared further in details of these procedures are described subgroups by genders of participants elsewhere in prior publications [3, 8] Demographic data were compared using Briefly, the image processing includes a Chi-square test motion correction and averaging of * Ethical approval: multiple volumetric T1 weighted images, This study was approved by the ethics removal of non-brain tissue using a hybrid review committee of Vietnam Military Medical watershed/surface deformation procedure, University 657 TẠP CHÍ Y - DƢỢC HỌC QUÂN SỰ SỐ CHUYÊN ĐỀ HÌNH THÁI HỌC-2017 RESULTS AND DISCUSSION Demographics of participants Table 1: Demographic characteristics of SZ patients and controls Age Groups ( Gender (n, %) ± SD) Male Female SZ 32.74 ± 10.13 26 (54.17) 13 (40.63) Control 34.54 ± 11.64 22 (45.83) 19 (59.38) p = 0.46 p = 0.23 The results in table showed that SZ patients did not differ from controls regarding age and gender Volumes of brain regions in SZ and control groups Table 2: Volumes of brain regions in SZ and control groups SZ (n = 39) Control (n = 40) Volume p ( ± SD) ( ± SD) 1153.40 ± 111.56 1208.51 ± 108.51 0.028a Total brain with ventricle/ICV 0.78 ± 0.06 0.80 ± 0.03 0.037b Total brain without ventricle 1131.59 ± 108.04 1191.95 ± 109.59 0.015a, b 2.21 ± 2.23 2.33 ± 2.58 0.013a Total cerebellum 108.66 ± 12.90 111.73 ± 10.25 0.24 Left cerebellum 53.41 ± 5.95 54.72 ± 4.99 0.29 Right cerebellum 55.25 ± 7.07 57.01 ± 5.41 0.21 Lateral ventricle 14.67 ± 5.97 11.07 ± 6.62 0.012b Left lateral ventricle 8.03 ± 3.26 5.88 ± 3.46 0.005a, b Right lateral ventricle 6.64 ± 2.80 5.19 ± 3.26 0.036 Third ventricle 1.12 ± 0.34 0.80 ± 0.34 0.0001a, b Fourth ventricle 1.66 ± 0.46 1.52 ± 0.49 0.17b Cerebrospinal fluid (CSF) 1.123 ± 0.29 1.09 ± 0.26 0.23b Intracranial volume (ICV) 1491.53 ± 154.82 1520.36 ± 131.14 0.37 Total brain with ventricle Brain stem b (a: Significant difference in male; b: Significant difference in female The measured unit for volumes of brain regions was in milliliter, excepting fortotal brain with ventricle/ICV that was expressed as a ratio number) 658 TẠP CHÍ Y - DƢỢC HỌC QUÂN SỰ SỐ CHUYÊN ĐỀ HÌNH THÁI HỌC-2017 Table showed no difference in ICV between SZ and control groups A significant reduction in total brain with ventricle, total brain with ventricle/ICV, and total brain without ventricle was found in SZ compared to those in controls (p values of 0.028, 0.037, and 0.015, respectively) In which, the significant difference was only for total brain with ventricle in male, total brain with ventricle/ICV in female, and total brain without ventricle in both genders Also, the brain stem volume was reduced in male SZ, whereas cerebellum structure unchanged The lateral, third, and fourth ventricles in SZ were enlarged Though SZ group did not differ from controls concerning the fourth ventricle and CSF volumes, but those indices did enlarge in female SZ Our results were consistent with those in previous studies [11] regarding lateral ventricle enlargement and brain changes in SZ The cerebellum volume was indifferent between SZ patients and controls, which was in line with several previous studies [7, 12], yet inconsistent with other reports [7] The reduction of brain was matched properly with changes in ventricle volume and CSF change in SZ [12] The volumes of GM and WM in the sample were shown in table 3, and an illustration of GM and WM extraction was demonstrated in figure Table 3: Volumes of GM and WM in SZ patients and controls Volume SZ (n = 39) ( ± SD) Control (n = 40) ( ± SD) p Total cortical GM 438.70 ± 49.83 454.94 ± 52.70 0.16a LH cortical GM 218.61 ±25.00 226.77 ± 26.21 0.16a RH cortical GM 220.09 ± 24.89 228.17 ± 26.55 0.16a Total cortical WM 498.03 ± 57.05 537.52 ± 51.69 0.001a, b LH cortical WM 248.33 ± 28.63 266.67 ± 26.21 0.004a, b RH cortical WM 249.71 ± 28.49 270.85 ± 28.90 0.000a, b Subcortical GM 58.75 ± 5.30 59.42 ± 55.17 0.58 606.16 ± 62.21 626.335 ± 63.50 0.156a Total GM (a: Significant difference in male; b: Significant difference in female; LH: Left hemisphere; RH: Right hemisphere The measured unit for volumes of brain regions was in milliliter) The results in table showed the reduction of left and right hemisphere WM volumes and of total WM volume in SZ GM did not reduce in SZ patients, but it did in male SZ subgroup Subcortical GM volume was indifferent between groups Our results were in accordance with those of previous studies in whole GM and WM [12], and also in concordance with recent longitudinal neuroimaging studies showing the progressive structural brain changes in GM [9, 10] 659 TẠP CHÍ Y - DƢỢC HỌC QUÂN SỰ SỐ CHUYÊN ĐỀ HÌNH THÁI HỌC-2017 About antipsychotic effect on brain structural change, a meta-analysis of longitudinal studies showed progressive GM decreases among SZ patients [10] All patients in that study were administered an antipsychotic medication that supposed to have an influence on slowing the progress of GM loss in SZ However, the effect of antipsychotic medications on cortical GM change appeared in a generation-dependent manner [10] Therefore, further studies on antipsychotic effects to brain changes should be encouraged The changes of WM in SZ patients were consistent with those in previous studies [5, 6] The reduction of WM in SZ patients might due to a decrease of number and size of axons in the brain, and diffusion tensor imaging in following studies should be elicited to firmly elucidate such raised issue Figure 1: Brain gray and white matter extraction (upper images: sagittal; lower images: axial) 660 TẠP CHÍ Y - DƢỢC HỌC QUÂN SỰ SỐ CHUYÊN ĐỀ HÌNH THÁI HỌC-2017 CONCLUSION Our results of MRI study in Vietnamese people support a notion of the reduction of gray and white matters and of brain volume in SZ REFERENCES Borgwardt S.J, Dickey C, Hulshoff Pol H, Whitford T.J, DeLisi L.E Workshop on defining the significance of progressive brain change in SZ: December 12, 2008 American College of Neuropsychopharmacology (ACNP) all-day satellite, Scottsdale, Arizona The rapporteurs' report Schizophr Res 2009, 112 (1 - 3), pp.32-45 Dale A.M, Fischl B, Sereno M.I Cortical surface-based analysis I Segmentation and surface reconstruction Neuroimage 1999, (2), pp.179-194 Desikan R.S, Segonne F, Fischl B, Quinn B.T, Dickerson B.C, Blacker D, Buckner R.L, Dale A.M, Maguire R.P, Hyman B.T, Albert M.S, Killiany R.J An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest Neuroimage 2006, 31 (3), pp.968-980 Fischl B, van der Kouwe A, Destrieux C, Halgren E, Segonne F, Salat D.H, Busa E, Seidman L.J, Goldstein J, Kennedy D, Caviness V, Makris N, Rosen B, Dale A.M Automatically parcellating the human cerebral cortex Cereb Cortex 2004, 14 (1), pp.11-22 Karbasforoushan H, Duffy B, Blackford J.U, Woodward N.D Processing speed impairment in SZ is mediated by white matter integrity Psychol Med 2015, 45 (1), pp.109-120 Kochunov P, Coyle T.R, Rowland L.M, Jahanshad N, Thompson P.M, Kelly S, Du X, Sampath H, Bruce H, Chiappelli J, Ryan M, Fisseha F, Savransky A, Adhikari B, Chen S, Paciga S.A, Whelan C.D, Xie Z, Hyde C.L, Chen X, Schubert C.R, O'Donnell P, Hong L.E Association of white matter with core cognitive deficits in patients with SZ JAMA Psychiatry 2017 Laidi C, d'Albis M.A, Wessa M, Linke J, Phillips M.L, Delavest M, Bellivier F, Versace A, Almeida J, Sarrazin S, Poupon C, Le Dudal K, Daban C, Hamdani N, Leboyer M, Houenou J Cerebellar volume in SZ and bipolar I disorder with and without psychotic features Acta Psychiatr Scand 2015, 131 (3), pp.223-233 Reuter M, Schmansky N.J, Rosas H.D, Fischl B Within-subject template estimation for unbiased longitudinal image analysis Neuroimage 2012, 61 (4), pp.1402-1418 Torres U.S, Duran F.L, Schaufelberger M.S, Crippa J.A, Louza M.R, Sallet P.C, Kanegusuku C.Y, Elkis H, Gattaz W.F, Bassitt D.P, Zuardi A.W, Hallak J.E, Leite C.C, Castro C.C, Santos A.C, Murray R.M, Busatto G.F Patterns of regional gray matter loss at different stages of SZ: A multisite, cross-sectional VBM study in first-episode and chronic illness Neuroimage Clin 2016, 12, pp.1-15 10 Vita A, De Peri L, Deste G, Barlati S, Sacchetti E The effect of antipsychotic treatment on cortical gray matter changes in SZ: Does the class matter? A meta-analysis and metaregression of longitudinal magnetic resonance imaging studies Biol Psychiatry 2015, 78 (6), pp.403-412 11 Weinberg D, Lenroot R, Jacomb I, Allen K, Bruggemann J, Wells R, Balzan R, Liu D, Galletly C, Catts S.V, Weickert C.S, Weickert T.W Cognitive subtypes of SZ characterized by differential brain volumetric reductions and cognitive decline JAMA Psychiatry 2016, 73 (12), pp.1251-1259 12 Shenton M.E, Whitford T.J, Kubicki M Structural neuroimaging in SZ: from methods to insights to treatments Dialogues Clin Neurosci 2010, 12 (3), pp.317-332 661 ... number and size of axons in the brain, and diffusion tensor imaging in following studies should be elicited to firmly elucidate such raised issue Figure 1: Brain gray and white matter extraction (upper... were in accordance with those of previous studies in whole GM and WM [12], and also in concordance with recent longitudinal neuroimaging studies showing the progressive structural brain changes in. .. results in table showed that SZ patients did not differ from controls regarding age and gender Volumes of brain regions in SZ and control groups Table 2: Volumes of brain regions in SZ and control