首发未服药精神分裂症全脑及局部白质脑网络拓扑改变
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摘要
目的:研究首次发病未经任何治疗的精神分裂症患者脑白质网络拓扑学特征。方法:采集42例首发未治疗精神分裂症患者、38例健康对照者进行弥散张量成像(diffusion tensor imaging, DTI)扫描,构建脑白质结构网络,计算拓扑属性。采用阳性和阴性症状量表(Positive and Negative Syndrome Scale, PANSS)评定患者症状严重程度。结果:患者全局拓扑属性相对保持完整,而节点拓扑属性显示双侧前、后扣带回、额上回等脑区较健康对照降低,且患者左侧后扣带回的节点拓扑属性与PANSS量表一般精神病理分呈负相关。结论:精神分裂症患者发病早期存在边缘系统及前额叶局部脑白质网络拓扑属性降低,而全脑白质拓扑架构保持相对完整。损害的局部边缘系统白质拓扑结构可能为精神分裂症大体精神症状行为表型所对应的脑网络方面的生物学标记,而前额叶拓扑结构损害可能构成该病内在的素质性生物学标记。
Objective: To study the cerebral white matter network in drug-naive first-episode schizophrenia patients(FESP). Methods: Topological characteristics of cerebral white matter network were calculated by using diffusion tensor imaging(DTI) data which were collected from 42 drug-naive FESP and 38 healthy volunteers. Patients' clinical state was evaluated using Positive and Negative Syndrome Scale(PANSS). Results: Patients showed relatively intact overall topological organizations, and deficient nodal topological properties primarily located in prefrontal gyrus and limbic system components such as bilateral anterior and posterior cingulate. The nodal topological character of the left posterior cingulate showed a negative correlation with PANSS general psychopathology scores. Conclusion: During the early phase of schizophrenia there are region-specific alterations in white matter topological measures. Limbic white matter topological dysfunction may be considered as a biomarker to reflect the general psychopathology. Prefrontal deficits are potential trait biomarkers and targets for negative symptom.
Objective: To study the cerebral white matter network in drug-naive first-episode schizophrenia patients(FESP). Methods: Topological characteristics of cerebral white matter network were calculated by using diffusion tensor imaging(DTI) data which were collected from 42 drug-naive FESP and 38 healthy volunteers. Patients' clinical state was evaluated using Positive and Negative Syndrome Scale(PANSS). Results: Patients showed relatively intact overall topological organizations, and deficient nodal topological properties primarily located in prefrontal gyrus and limbic system components such as bilateral anterior and posterior cingulate. The nodal topological character of the left posterior cingulate showed a negative correlation with PANSS general psychopathology scores. Conclusion: During the early phase of schizophrenia there are region-specific alterations in white matter topological measures. Limbic white matter topological dysfunction may be considered as a biomarker to reflect the general psychopathology. Prefrontal deficits are potential trait biomarkers and targets for negative symptom.
引文
1 Wernicke C.Grundrisse der Psychiatrie.Leipzig.Germany:Thieme,1906
2 Stephan KE,Friston KJ,Frith CD.Dysconnection in schizophrenia:from abnormal synaptic plasticity to failures of selfmonitoring.Schizophrenia Bulletin,2009,35(3):509-527
3 Skudlarski P,Schretlen DJ,Thaker GK,et al.Diffusion tensor imaging white matter endophenotypes in patients with schizophrenia or psychotic bipolar disorder and their relatives.The American Journal of Psychiatry,2013,170(8):886-898
4 Iturria-Medina Y,Sotero RC,Canales-Rodriguez EJ,et al.Studying the human brain anatomical network via diffusionweighted MRI and Graph Theory.NeuroImage,2008,40(3):1064-1076
5 Grunder G,Vernaleken I,Muller MJ,et al.Subchronic haloperidol downregulates dopamine synthesis capacity in the brain of schizophrenic patients in vivo.Neuropsychopharmacology:Official Publication of the American College of Neuropsychopharmacology,2003,28(4):787-794
6 Elkashef AM,Doudet D,Bryant T,et al.6-(18)F-DOPAPET study in patients with schizophrenia.Positron emission tomography.Psychiatry Research,2000,100(1):1-11
7 Nelson MD,Saykin AJ,Flashman LA,et al.Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging:a meta-analytic study.Archives of General Psychiatry,1998,55(5):433-440
8 Macrae CN,Moran JM,Heatherton TF,et al.Medial prefrontal activity predicts memory for self.Cerebral Cortex(New York,NY:1991),2004,14(6):647-654
9 Fusar-Poli P,Bechdolf A,Taylor MJ,et al.At risk for schizophrenic or affective psychoses?A meta-analysis of DSM/ICD diagnostic outcomes in individuals at high clinical risk.Schizophrenia Bulletin,2013,39(4):923-932
10 Fusar-Poli P,Bonoldi I,Yung AR,et al.Predicting psychosis:meta-analysis of transition outcomes in individuals at high clinical risk.Archives of General Psychiatry,2012,69(3):220-229
11 Diwadkar VA,Montrose DM,Dworakowski D,et al.Genetically predisposed offspring with schizotypal features:an ultra high-risk group for schizophrenia?Progress in Neuropsychopharmacology&Biological Psychiatry,2006,30(2):230-238
12 Zhang Z,Liao W,Chen H,et al.Altered functionalstructural coupling of large-scale brain networks in idiopathic generalized epilepsy.Brain:a Journal of Neurology,2011,134(Pt 10):2912-2928
13 Rubinov M,Sporns O.Complex network measures of brain connectivity:uses and interpretations.NeuroImage,2010,52(3):1059-1069
14 Davis KL,Kahn RS,Ko G,et al.Dopamine in schizophrenia:a review and reconceptualization.The American Journal of Psychiatry,1991,148(11):1474-1486
15 Storey JD.A direct approach to false discovery rates.Journal of the Royal Statistical Society:Series B(Statistical Methodology),2002,64(3):479-498
16 Wang Q,Cheung C,Deng W,et al.White-matter microstructure in previously drug-naive patients with schizophrenia after 6 weeks of treatment.Psychological Medicine,2013,43(11):2301-2309
17 Piantadosi PT,Floresco SB.Prefrontal cortical GABA trans mission modulates discrimination and latent inhibition of conditioned fear:relevance for schizophrenia.Neuropsychopharmacology:Official Publication of the American College of Neuropsychopharmacology,2014,39(10):2473-2484
18 Snitz BE,MacDonald A,3rd,Cohen JD,et al.Lateral and medial hypofrontality in first-episode schizophrenia:functional activity in a medication-naive state and effects of short-term atypical antipsychotic treatment.The American Journal of Psychiatry,2005,162(12):2322-2329
19 van Veelen NM,Vink M,Ramsey NF,et al.Prefrontal lobe dysfunction predicts treatment response in medication-naive first-episode schizophrenia.Schizophrenia Research,2011,129(2-3):156-162
20 Gur RE,Loughead J,Kohler CG,et al.Limbic activation associated with misidentification of fearful faces and flat affect in schizophrenia.Archives of General Psychiatry,2007,64(12):1356-1366
21 Lahti AC,Weiler MA,Holcomb HH,et al.Modulation of limbic circuitry predicts treatment response to antipsychotic medication:a functional imaging study in schizophrenia.Neuropsychopharmacology:official publication of the American College of Neuropsychopharmacology,2009,34(13):2675-2690
22 Lui S,Li T,Deng W,et al.Short-term effects of antipsychotic treatment on cerebral function in drug-naive first-episode schizophrenia revealed by“resting state”functional magnetic resonance imaging.Archives of General Psychiatry,2010,67(8):783-792
23 Catani M,Dell'acqua F,Thiebaut de Schotten M.A revised limbic system model for memory,emotion and behaviour.Neuroscience and Biobehavioral Reviews,2013,37(8):1724-1737
24 Farkas N,Lendeckel U,Dobrowolny H,et al.Reduced density of ADAM 12-immunoreactive oligodendrocytes in the anterior cingulate white matter of patients with schizophrenia.The World Journal of Biological Psychiatry:the Official Journal of the World Federation of Societies of Biological Psychiatry,2010,11(3):556-566
25 van den Heuvel MP,Mandl RC,Stam CJ,et al.Aberrant frontal and temporal complex network structure in schizophrenia:a graph theoretical analysis.The Journal of Neuroscience:the Official Journal of the Society for Neuroscience,2010,30(47):15915-15926
26 Menon V.Large-scale brain networks and psychopathology:a unifying triple network model.Trends in Cognitive Sciences,2011,15(10):483-506
27 Palaniyappan L,Liddle PF.Does the salience network play a cardinal role in psychosis?An emerging hypothesis of insular dysfunction.Journal of Psychiatry&Neuroscience:JPN,2012,37(1):17-27
28 Sambataro F,Blasi G,Fazio L,et al.Treatment with olanzapine is associated with modulation of the default mode network in patients with Schizophrenia.Neuropsychopharmacology:Official Publication of the American College of Neuropsychopharmacology,2010,35(4):904-912
29 Carter CS,MacDonald AW,3rd,Ross LL,et al.Anterior cingulate cortex activity and impaired self-monitoring of performance in patients with schizophrenia:an eventrelated fMRI study.The American Journal of Psychiatry,2001,158(9):1423-1428
30 Kubicki M,Westin CF,Nestor PG,et al.Cingulate fasciculus integrity disruption in schizophrenia:a magnetic resonance diffusion tensor imaging study.Biological Psychiatry,2003,54(11):1171-1180
31 Maddock RJ.The retrosplenial cortex and emotion:new insights from functional neuroimaging of the human brain.Trends in Neurosciences,1999,22(7):310-316
32 Fornito A,Yoon J,Zalesky A,et al.General and specific functional connectivity disturbances in first-episode schizophrenia during cognitive control performance.Biological Psychiatry,2011,70(1):64-72
33 Collin G,Kahn RS,de Reus MA,et al.Impaired rich club connectivity in unaffected siblings of schizophrenia patients.Schizophrenia Bulletin,2014,40(2):438-448
34 Fornito A,Zalesky A,Pantelis C,et al.Schizophrenia,neuroimaging and connectomics.NeuroImage,2012,62(4):2296-2314
2 Stephan KE,Friston KJ,Frith CD.Dysconnection in schizophrenia:from abnormal synaptic plasticity to failures of selfmonitoring.Schizophrenia Bulletin,2009,35(3):509-527
3 Skudlarski P,Schretlen DJ,Thaker GK,et al.Diffusion tensor imaging white matter endophenotypes in patients with schizophrenia or psychotic bipolar disorder and their relatives.The American Journal of Psychiatry,2013,170(8):886-898
4 Iturria-Medina Y,Sotero RC,Canales-Rodriguez EJ,et al.Studying the human brain anatomical network via diffusionweighted MRI and Graph Theory.NeuroImage,2008,40(3):1064-1076
5 Grunder G,Vernaleken I,Muller MJ,et al.Subchronic haloperidol downregulates dopamine synthesis capacity in the brain of schizophrenic patients in vivo.Neuropsychopharmacology:Official Publication of the American College of Neuropsychopharmacology,2003,28(4):787-794
6 Elkashef AM,Doudet D,Bryant T,et al.6-(18)F-DOPAPET study in patients with schizophrenia.Positron emission tomography.Psychiatry Research,2000,100(1):1-11
7 Nelson MD,Saykin AJ,Flashman LA,et al.Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging:a meta-analytic study.Archives of General Psychiatry,1998,55(5):433-440
8 Macrae CN,Moran JM,Heatherton TF,et al.Medial prefrontal activity predicts memory for self.Cerebral Cortex(New York,NY:1991),2004,14(6):647-654
9 Fusar-Poli P,Bechdolf A,Taylor MJ,et al.At risk for schizophrenic or affective psychoses?A meta-analysis of DSM/ICD diagnostic outcomes in individuals at high clinical risk.Schizophrenia Bulletin,2013,39(4):923-932
10 Fusar-Poli P,Bonoldi I,Yung AR,et al.Predicting psychosis:meta-analysis of transition outcomes in individuals at high clinical risk.Archives of General Psychiatry,2012,69(3):220-229
11 Diwadkar VA,Montrose DM,Dworakowski D,et al.Genetically predisposed offspring with schizotypal features:an ultra high-risk group for schizophrenia?Progress in Neuropsychopharmacology&Biological Psychiatry,2006,30(2):230-238
12 Zhang Z,Liao W,Chen H,et al.Altered functionalstructural coupling of large-scale brain networks in idiopathic generalized epilepsy.Brain:a Journal of Neurology,2011,134(Pt 10):2912-2928
13 Rubinov M,Sporns O.Complex network measures of brain connectivity:uses and interpretations.NeuroImage,2010,52(3):1059-1069
14 Davis KL,Kahn RS,Ko G,et al.Dopamine in schizophrenia:a review and reconceptualization.The American Journal of Psychiatry,1991,148(11):1474-1486
15 Storey JD.A direct approach to false discovery rates.Journal of the Royal Statistical Society:Series B(Statistical Methodology),2002,64(3):479-498
16 Wang Q,Cheung C,Deng W,et al.White-matter microstructure in previously drug-naive patients with schizophrenia after 6 weeks of treatment.Psychological Medicine,2013,43(11):2301-2309
17 Piantadosi PT,Floresco SB.Prefrontal cortical GABA trans mission modulates discrimination and latent inhibition of conditioned fear:relevance for schizophrenia.Neuropsychopharmacology:Official Publication of the American College of Neuropsychopharmacology,2014,39(10):2473-2484
18 Snitz BE,MacDonald A,3rd,Cohen JD,et al.Lateral and medial hypofrontality in first-episode schizophrenia:functional activity in a medication-naive state and effects of short-term atypical antipsychotic treatment.The American Journal of Psychiatry,2005,162(12):2322-2329
19 van Veelen NM,Vink M,Ramsey NF,et al.Prefrontal lobe dysfunction predicts treatment response in medication-naive first-episode schizophrenia.Schizophrenia Research,2011,129(2-3):156-162
20 Gur RE,Loughead J,Kohler CG,et al.Limbic activation associated with misidentification of fearful faces and flat affect in schizophrenia.Archives of General Psychiatry,2007,64(12):1356-1366
21 Lahti AC,Weiler MA,Holcomb HH,et al.Modulation of limbic circuitry predicts treatment response to antipsychotic medication:a functional imaging study in schizophrenia.Neuropsychopharmacology:official publication of the American College of Neuropsychopharmacology,2009,34(13):2675-2690
22 Lui S,Li T,Deng W,et al.Short-term effects of antipsychotic treatment on cerebral function in drug-naive first-episode schizophrenia revealed by“resting state”functional magnetic resonance imaging.Archives of General Psychiatry,2010,67(8):783-792
23 Catani M,Dell'acqua F,Thiebaut de Schotten M.A revised limbic system model for memory,emotion and behaviour.Neuroscience and Biobehavioral Reviews,2013,37(8):1724-1737
24 Farkas N,Lendeckel U,Dobrowolny H,et al.Reduced density of ADAM 12-immunoreactive oligodendrocytes in the anterior cingulate white matter of patients with schizophrenia.The World Journal of Biological Psychiatry:the Official Journal of the World Federation of Societies of Biological Psychiatry,2010,11(3):556-566
25 van den Heuvel MP,Mandl RC,Stam CJ,et al.Aberrant frontal and temporal complex network structure in schizophrenia:a graph theoretical analysis.The Journal of Neuroscience:the Official Journal of the Society for Neuroscience,2010,30(47):15915-15926
26 Menon V.Large-scale brain networks and psychopathology:a unifying triple network model.Trends in Cognitive Sciences,2011,15(10):483-506
27 Palaniyappan L,Liddle PF.Does the salience network play a cardinal role in psychosis?An emerging hypothesis of insular dysfunction.Journal of Psychiatry&Neuroscience:JPN,2012,37(1):17-27
28 Sambataro F,Blasi G,Fazio L,et al.Treatment with olanzapine is associated with modulation of the default mode network in patients with Schizophrenia.Neuropsychopharmacology:Official Publication of the American College of Neuropsychopharmacology,2010,35(4):904-912
29 Carter CS,MacDonald AW,3rd,Ross LL,et al.Anterior cingulate cortex activity and impaired self-monitoring of performance in patients with schizophrenia:an eventrelated fMRI study.The American Journal of Psychiatry,2001,158(9):1423-1428
30 Kubicki M,Westin CF,Nestor PG,et al.Cingulate fasciculus integrity disruption in schizophrenia:a magnetic resonance diffusion tensor imaging study.Biological Psychiatry,2003,54(11):1171-1180
31 Maddock RJ.The retrosplenial cortex and emotion:new insights from functional neuroimaging of the human brain.Trends in Neurosciences,1999,22(7):310-316
32 Fornito A,Yoon J,Zalesky A,et al.General and specific functional connectivity disturbances in first-episode schizophrenia during cognitive control performance.Biological Psychiatry,2011,70(1):64-72
33 Collin G,Kahn RS,de Reus MA,et al.Impaired rich club connectivity in unaffected siblings of schizophrenia patients.Schizophrenia Bulletin,2014,40(2):438-448
34 Fornito A,Zalesky A,Pantelis C,et al.Schizophrenia,neuroimaging and connectomics.NeuroImage,2012,62(4):2296-2314