Gray and white matter reduction in schizophrenia patients

Nội dung text: Gray and white matter reduction in schizophrenia patients

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