精神分裂症一级亲属静息状态的功能磁共振研究
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摘要
目的:采用功能磁共振技术(functional magnetic resonance imaging,fMRI),探讨精神分裂症患者一级亲属是否存在静息状态的脑功能异常以及脑功能异常区域定位。
方法:选择13例符合第四版美国精神障碍与统计手册(Diagnosticand statistical manual,fourth edition DSM-IV)诊断标准的精神分裂症患者的同胞为研究组,13例与精神分裂症患者同胞年龄、性别、受教育年限相匹配的正常人为正常对照组,两组均进行静息状态的血氧水平依赖(blood oxygen level dependent,BOLD)的脑功能成像。采用统计参数图(statistical parametric mapping,SPM2)经头部运动检测、去基线漂移、空间标准化以及高斯平滑后用局部一致(regional homogeneity,ReHo)方法处理fMRI数据。为比较精神分裂症一级亲属和正常对照在静息状态下的脑功能差异,对以ReHo方法得到的两组KCC(Kendall coefficient concordance)图像中相应位置的体素逐个进行两样本t检验。
结果:与正常人相比,精神分裂症一级亲属在静息状态下脑的BOLD信号的ReHo普遍降低(P＜0.005)。ReHo降低的脑区有双侧额中回、颞中回、扣带回、小脑扁桃体;左侧额下回、顶下小叶、前额叶中部背侧皮层;右侧额上回及前额叶中部背侧皮层。ReHo增高的脑区有右侧楔前叶及颞上回。
结论:精神分裂症一级亲属在静息状态下存在脑功能异常。静息状态下血氧依赖水平的fMRI将成为精神分裂症的重要研究手段。
Objective: To explore whether and where abnormal brain activity exists in the first-degree relatives of schizophrenia during resting state by using functional magnetic resonance imaging ;and the mapping of abnormal area in fMRI of the relatives of schizophrenia.
Methods: 13 first degree relatives of schizophrenia(study group) and 13 healthy controls(control group)were enrolled in this study. They all underwent fMRI in resting state. The newly published ReHo approach was applied for fMRI data analysis after realignment, registration, normalization and smooth in SPM2. For exploring the difference of fMRI between the schizophrenic and controls, a two-sample t test was performed on the individual in a voxel by voxel manner. Resulted statistical map was set a combined threshold of p<0.005 and the number of voxel>5.
Results: Compared to control group, the first-degree relatives of schizophrenia showed decreased ReHo of BOLD signal in resting brain compared with control subjects (P<0.005) . The decreased ReHo was distributed over bilateral medial frontal, middle temporal, cingulate gyrus and cerebellar tonsil; the left inferior frontal gyrus, inferior parietal lobule and dorsolateral prefrontal cortex; the right superior frontal gyrus and dorsolateral prefrontal cortex. The increased ReHo was distributed in the right precuneus and superior temporal gyrus.
Conclusions:The resting state fMRI study showed that abnormal brain activity in the first-degree relatives of schizophrenia might exist in resting state. BOLD-fMRI will be an important research means in schizophasia.
方法:选择13例符合第四版美国精神障碍与统计手册(Diagnosticand statistical manual,fourth edition DSM-IV)诊断标准的精神分裂症患者的同胞为研究组,13例与精神分裂症患者同胞年龄、性别、受教育年限相匹配的正常人为正常对照组,两组均进行静息状态的血氧水平依赖(blood oxygen level dependent,BOLD)的脑功能成像。采用统计参数图(statistical parametric mapping,SPM2)经头部运动检测、去基线漂移、空间标准化以及高斯平滑后用局部一致(regional homogeneity,ReHo)方法处理fMRI数据。为比较精神分裂症一级亲属和正常对照在静息状态下的脑功能差异,对以ReHo方法得到的两组KCC(Kendall coefficient concordance)图像中相应位置的体素逐个进行两样本t检验。
结果:与正常人相比,精神分裂症一级亲属在静息状态下脑的BOLD信号的ReHo普遍降低(P＜0.005)。ReHo降低的脑区有双侧额中回、颞中回、扣带回、小脑扁桃体;左侧额下回、顶下小叶、前额叶中部背侧皮层;右侧额上回及前额叶中部背侧皮层。ReHo增高的脑区有右侧楔前叶及颞上回。
结论:精神分裂症一级亲属在静息状态下存在脑功能异常。静息状态下血氧依赖水平的fMRI将成为精神分裂症的重要研究手段。
Objective: To explore whether and where abnormal brain activity exists in the first-degree relatives of schizophrenia during resting state by using functional magnetic resonance imaging ;and the mapping of abnormal area in fMRI of the relatives of schizophrenia.
Methods: 13 first degree relatives of schizophrenia(study group) and 13 healthy controls(control group)were enrolled in this study. They all underwent fMRI in resting state. The newly published ReHo approach was applied for fMRI data analysis after realignment, registration, normalization and smooth in SPM2. For exploring the difference of fMRI between the schizophrenic and controls, a two-sample t test was performed on the individual in a voxel by voxel manner. Resulted statistical map was set a combined threshold of p<0.005 and the number of voxel>5.
Results: Compared to control group, the first-degree relatives of schizophrenia showed decreased ReHo of BOLD signal in resting brain compared with control subjects (P<0.005) . The decreased ReHo was distributed over bilateral medial frontal, middle temporal, cingulate gyrus and cerebellar tonsil; the left inferior frontal gyrus, inferior parietal lobule and dorsolateral prefrontal cortex; the right superior frontal gyrus and dorsolateral prefrontal cortex. The increased ReHo was distributed in the right precuneus and superior temporal gyrus.
Conclusions:The resting state fMRI study showed that abnormal brain activity in the first-degree relatives of schizophrenia might exist in resting state. BOLD-fMRI will be an important research means in schizophasia.
引文
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4 Heydebrand G. Cognitive deficits in the families of patients with schizophrenia. Curt Opin Psychiatry, 2006, 19(3): 277.
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9 Job DE, Whalley THC, Johnstone EC, et al. Grey matter changes over time in high risk subjects developing schizophrenia. Neurolmage ,2005;25 (4) :1023 —1030.
10 Thermenos HW , Seidman LJ, BreiterH, et al. Functional magnetic resonance imaging during auditory verbal working memory in nonpsyehotic relatives of persons with schizophrenia: a pilot study.Bid Psychiatry, 2004;55:490-500.
11 Habel U, Klein M, shah NJ, et al. Genetic Load on Amygdala Hypofunc-tion During Sadness in Nonaffected Brothers of Schizophrenia Patients. Am J Psychiatry, 2004, 161: 1806—1813.
12 Foucher JR,Otzenberger H,Gounot D.Where arousal meets attention: a simultaneous fMRI and EEG recording study .Neuroimage 2004, 22: 688-697.
13 Masoyer B, Zago L, Mellet E, et al. Cortical network for working memory and executive function sustain the conscious resting state in man brain[J]. Res Bull,2001,54(3): 287—298.
14 Ma L, WangB, Chen X, etal. Detecting, functional connectivity in the resting brain: a comparison between ICA and CCA. Magn Reson Imaging, 2007, 25(1):47—56.
15 Cao Q, Zang Y, Sun L, et al. Abnormal neural activity in children with attention deficit hyperactivity disorder: a resting state functional magnetic resonance imaging study. Neuroreport, 2006, 17: 1033—1036.
16 Zang YF, Jiang TZ, Lu YL, etal. Regional homogeneity approach to fMRI data analysis. Neuroimage, 2004, 22(1): 394—400.
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20 Kendall M, Gibbons JD. Rank Correlation Methods. Oxford:Oxford University Press, 1990.
21 RaichleME, Gusnard DA. Intrinsic brain activity sets the stage for expression of motivated behavior. J Comp Neurol, 2005,493: 167 -176.
22 Greicius MD, Krasnow B,Reiss AL,et al.Functional connectivity in the restingbrain:a network analysis of the default mode hypothesis. PNAS 2003, 100:253-258.
23 Biswal B, Yetkin FZ, Haughton VM, et al. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI.Magn ResonMed, 1995,34:537-541.
24 Morgan VL, Price RR, Arain A, et al. Resting functional MRI with temporal clustering analysis for localization of epileptic activity without EEC Neurolmage,2004, 21: 473-481.
25 Friston KJ, Frith CD, Frackowiak RSJ. Time-dependent changes in effective connectivity measured with PET. Human Brain Mapping, 1993,1:69-80.
26 AndrewM, Mc Intosh,MRCPsych, LK. Neurop sychological impairments in people with schizophrenia or bipolar disorder and their unaffected relatives. The British Journal of Psychiatry, 2005,186: 378-385.
27 Cadenhead KS, Light GA , Shafer KM , et al. P50 Suppression in individuals at risk for schizophrenia: the convergence of clinical, familial, and vulnerability marker risk assessment. Biol Psychiatry , 2005, 57(12): 1504.
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30 Keri S, Kelemen O, Benedek G, et al. Different traitmarkers for schizphrenia and bipolar disorder: a neuro cognitive approach. PsycholMed,2001, 31 (5): 915-922.
31 Wible CG, Shenton ME, Fischer IA. et al. Parcellation of the human prefrontal cortex using MRI [J]. Psychiatry Res. 1997,76(1): 29-40.
32 Dierks T, Lindon DEJ., Jandl M..et al. Activation of Heschl's gyrus during auditory hallucinations[J]. Neuron. 1999,22:615- 621.
33 J.H. Fallon, I.O. Opole and S.G Potkin, The neuroanatomy of schizophrenia: circuitry and neurotransmitter systems, Clin. Neurosci. Res. 77(2003), pp. 77-107.
34 Simonotto, Flett E, Shillcock S, et al. Event—related fMRI of word classification and successful word recognition in subjects at genetically enhanced risk of schizophrenia. Psychological Medicine, 2006, 36: 1427—1439.
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[1] Raedler TJ , Knable MB , Weinberger DR. Schizophrenia as a developmental disorder of the cerebral cortex. Curr Opin Neurobiol. 1998, 8:157—161.
[2] Gottesman II ,Gould TD. Theendophenotypeconceptin psychiatry:etymologyandstrategicintentions.AmJPsychiatry,2003;160:636-645.
[31 RomanT, Schmitz M, Polanczyk GV, et al. Further evidence for the association between attention deficit hyperactivity disorder and beta-hydroxylase gene. Am J Med Genet, 2002, 114: 154—158.
[4] Niznikiewicz MA, Marek K, Martha ES. Recent structural and functional imaging findings in schizophrenia[J]. Curr Opin in Psychiatry,2003,16(2): 123-147.
[5] Tost H, EndeG, RufM, et al. Functional imaging research in schizophrenia[J].Int Rev Neurobiol, 2005, 67: 95-118.
[6] Liang M , Zhou Y, Jiang T, et al. Widespread functional disconnectivity in schizophrenia with resting -state functional magnetic resonance imaging. Brain Imaging Neuroreport, 2006, 17(2): 209—213
[71 Zhou Y, Liang M, Jiang T, et al. Functional dysconnectivity of the dorsolateral prefrontal codex in first-episode schizophrenia using resting-state fMRI. Neurosci Lett, 2007, 417(3): 297—302
[8]Hai Hong L. Decreased regional homogeneity in schizophrenia: a resting state functional magnetic resonance imaging study. Neuroreport, 2006, 17(1): 19—22
[9] Simonotto, Flett E, Shillcock S, et al. Event—related fMRI of word classification and successful word recognition in subjects at genetically enhance drisk of schizophrenia. Psychological Medicine, 2006, 36: 1427—1439.
[10] Whalley HC, Simonotto E, Moorhead W, et al. Functional imaging as a predictor of schizophrenia. Biological Psychiatry, 2006, 60(5): 454—462.
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2 Gottesman II , Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry, 2003: 160: 636—645.
3 TsuangMJ, etal: Acta Psychiatr Scand. 1999 (suppl 395): 2-11.
4 Heydebrand G. Cognitive deficits in the families of patients with schizophrenia. Curt Opin Psychiatry, 2006, 19(3): 277.
5 Jones LA, Cardno AG, Sanders RD, et al. Sustmned and selective attention as measures of genetic liability to schizophrenia. SchizophrRes, 2001, 48(2-3):263.
6 NiznikiewiczMA, Marek K, Martha ES. Recent structural and functional imaging findings in schizophrenia[J]. Curr Opin in Psychiatry,2003,16(2): 123-147.
7 Tost H, EndeG, RufM, et al. Functional imaging research in schizophrenia[J].Int Rev Neurobiol, 2005, 67: 95-118.
8 Styner M, Lieberman JA, McClure RK,et al. Morphometric analysis of lateral ventricles in schizophrenia and healthy controls regarding genetic and disease-specific factors.ProcNatl Acad Sci USA, 2005,102(13):4872- 4877.
9 Job DE, Whalley THC, Johnstone EC, et al. Grey matter changes over time in high risk subjects developing schizophrenia. Neurolmage ,2005;25 (4) :1023 —1030.
10 Thermenos HW , Seidman LJ, BreiterH, et al. Functional magnetic resonance imaging during auditory verbal working memory in nonpsyehotic relatives of persons with schizophrenia: a pilot study.Bid Psychiatry, 2004;55:490-500.
11 Habel U, Klein M, shah NJ, et al. Genetic Load on Amygdala Hypofunc-tion During Sadness in Nonaffected Brothers of Schizophrenia Patients. Am J Psychiatry, 2004, 161: 1806—1813.
12 Foucher JR,Otzenberger H,Gounot D.Where arousal meets attention: a simultaneous fMRI and EEG recording study .Neuroimage 2004, 22: 688-697.
13 Masoyer B, Zago L, Mellet E, et al. Cortical network for working memory and executive function sustain the conscious resting state in man brain[J]. Res Bull,2001,54(3): 287—298.
14 Ma L, WangB, Chen X, etal. Detecting, functional connectivity in the resting brain: a comparison between ICA and CCA. Magn Reson Imaging, 2007, 25(1):47—56.
15 Cao Q, Zang Y, Sun L, et al. Abnormal neural activity in children with attention deficit hyperactivity disorder: a resting state functional magnetic resonance imaging study. Neuroreport, 2006, 17: 1033—1036.
16 Zang YF, Jiang TZ, Lu YL, etal. Regional homogeneity approach to fMRI data analysis. Neuroimage, 2004, 22(1): 394—400.
17 Liu HH, Hu ZN, Hang M, et al. Decreased regional homogeneity in schizophrenia : a resting state functional magnetic resonance : imaging study. Neuroreport, 2006, 17(1): 19—22.
18 Katanoda K, Matsuda Y, Sugishita M, et al. A spatial -temporal regression model for the analysis of functional MRI data. Neuroimage, 2002,17: 1415-1428.
19 Tononi G, McIntosh AR, Russell DP, et al. Functional clustering: identifying strongly interactive brain regions in neuroimaging data. Neuroimage, 1998, 7: 133-149.
20 Kendall M, Gibbons JD. Rank Correlation Methods. Oxford:Oxford University Press, 1990.
21 RaichleME, Gusnard DA. Intrinsic brain activity sets the stage for expression of motivated behavior. J Comp Neurol, 2005,493: 167 -176.
22 Greicius MD, Krasnow B,Reiss AL,et al.Functional connectivity in the restingbrain:a network analysis of the default mode hypothesis. PNAS 2003, 100:253-258.
23 Biswal B, Yetkin FZ, Haughton VM, et al. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI.Magn ResonMed, 1995,34:537-541.
24 Morgan VL, Price RR, Arain A, et al. Resting functional MRI with temporal clustering analysis for localization of epileptic activity without EEC Neurolmage,2004, 21: 473-481.
25 Friston KJ, Frith CD, Frackowiak RSJ. Time-dependent changes in effective connectivity measured with PET. Human Brain Mapping, 1993,1:69-80.
26 AndrewM, Mc Intosh,MRCPsych, LK. Neurop sychological impairments in people with schizophrenia or bipolar disorder and their unaffected relatives. The British Journal of Psychiatry, 2005,186: 378-385.
27 Cadenhead KS, Light GA , Shafer KM , et al. P50 Suppression in individuals at risk for schizophrenia: the convergence of clinical, familial, and vulnerability marker risk assessment. Biol Psychiatry , 2005, 57(12): 1504.
28 Kom H. Schizophrenia and eye movement—a new diagnostic and therapeutic concept[J]. Med Hypotheses, 2004, 62:29-34.
29 Seidman LJ,Faraone SV,Goldstein JM,etal.Left hippocampal volume as a vulner ability indicator for schizophrenia:a magnetic resonance Imaging morphometric study of nonpsychotic first -degree relatives. Arch Gen Psychiatry,2002,59:839-849.
30 Keri S, Kelemen O, Benedek G, et al. Different traitmarkers for schizphrenia and bipolar disorder: a neuro cognitive approach. PsycholMed,2001, 31 (5): 915-922.
31 Wible CG, Shenton ME, Fischer IA. et al. Parcellation of the human prefrontal cortex using MRI [J]. Psychiatry Res. 1997,76(1): 29-40.
32 Dierks T, Lindon DEJ., Jandl M..et al. Activation of Heschl's gyrus during auditory hallucinations[J]. Neuron. 1999,22:615- 621.
33 J.H. Fallon, I.O. Opole and S.G Potkin, The neuroanatomy of schizophrenia: circuitry and neurotransmitter systems, Clin. Neurosci. Res. 77(2003), pp. 77-107.
34 Simonotto, Flett E, Shillcock S, et al. Event—related fMRI of word classification and successful word recognition in subjects at genetically enhanced risk of schizophrenia. Psychological Medicine, 2006, 36: 1427—1439.
35 Katanoda K,Yoshikawa K,Sugishita M,et al . A functional MRI study on the neural substrates for writing[J]. Hunn Brain Mapp, 2001, 13(1): 34-42.
36 Preibisch C, Berg D, Hofmann E, et al. Cerebral activation patterns in patients with writer's cramp: a functional magnetic resonance imaging study[J]. J Neural, 2001, 248(1): 10-17.
37 Wassink TH, Andreasen NC, Nopoulos P.et al. Cerebellar morphology as a predictor of symptom and psychosocial outcome in schizophrenia[J]. Biol Psychiatry.1999,45(1):41-48.
38 Neckelmann G, Specht K, Lund A.et al. Mr morphometry analysis of grey matter volume reduction in schizophrenia: association with hallucinations [J]. Int J Neurosci. 2006,116(1):9-23.
39 Callicott JH, Egan MF, Mattay VS,et al. Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact sibling of patients with schizophrenia. Am J Psychiatry, 2003; 160: 709-719.
40 Whalley HC, Simonotto E, Moorhead W, et al. Functional imaging as a predictor of schizophrenia. Biological Psychiatry, 2006, 60(5): 454—462.
41 Cavanna AE, Trimble MR. The precuneus: a review of its functional anatomy and behavioural correlates[J]. Brain,2006,129(Pt 3): 564-583.
42 Ralchle ME, Macleod AM, SnyderAZ, etal. A default mode of brain function[J]. PNAS, 2001, 98(2): 676—682.
43 Roman T, Schmitz M, Polanczyk GV, et al. Further evidence for the association between attention deficit hyperactivity disorder and beta-hydroxylase gene. American Journal of Medical Genetics, 2002, 114: 154—158.
44 Kent L, Doerry U, Hardy E et al. Evidence that variation at the serotonin transporter gene influences susceptibility to attention deficit hyperactivity disorder (ADHD): analysis and pooled analysis. Molecular Psychiatry, 2002, 7: 908—912.
45 Bernice P,Madhavi R,Chella K,etal.Theutility of neuro physiological markers in the study of alcoholism[J].ClinNeuro physiol,2005,116,993-1018.
46 Hasler G, Drevets WC, Manji HK, et al. Discovering endophenotypes for major depression. Neuropsychopharmacology,2004; 29: 1765—1781.
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