精神病未治疗期对首发未服药精神分裂症脑白质完整性的影响

目的 探讨精神病未治疗期(DUP)对首发未服药精神分裂症患者脑白质完整性的影响.方法 应用汉化的诺丁汉发病症状量表评定39例首发未服药精神分裂症患者的DUP,以其中位数为界将患者分为长DUP组和短DUP组,同时比较两组患者的性别构成、年龄、受教育年限、阳性和阴性症状量表总分.采用自旋回波序列得到弥散张量磁共振成像资料,以DTI-Studi0软件和统计参数图软件(SPM5)对所得图像进行预处理,得到的分子各向异性分数(FA)图像在SPM5软件中进行两样本t检验,获得两组FA差异统计参数图.结果 两组患者性别构成、年龄、受教育年限、阳性和阴性症状量表总分比较差异无统计学意义(P＞0.05).在P值小于0.001(未校正)水平下,长DUP组患者大脑右侧前扣带束(x=8,y=40,z=24)和左侧前额叶白质(x=32,y=34,z=4)FA值较短DUP组降低.结论 延长的DUP会降低首发未服药精神分裂症患者脑白质的完整性.     

精神分裂症早发患者脑白质的弥散张量成像研究

目的 分析发病年龄<18岁的早发精神分裂症(early-onset schizophrenia,EOS)患者脑结构连接的变化.方法 对26例EOS患者(患者组)和23名健康对照(对照组)全脑进行磁共振弥散张量成像,2组图像经过DTIstudio软件和统计参数图5(SPM5)软件包进行标准化、平滑等预处理后,再以SPM5软件包对2组全脑白质分数各向异性(FA)值图像进行两样本t检验.结果 (1)患者组脑白质FA值较对照组显著降低的脑区有:胼胝体体部及相邻双侧前扣带[蒙特利尔脑科学研究所(MNI)坐标:3、16、23;体素集合=1003体素]、左侧颞叶区域(MNI坐标:-28、28、30;体素集合=170体素)、左侧前额叶区域(MNI坐标:-28、28、30;体素集合=99体素)、右侧前额叶区域(MNI坐标:48、-10、54;体素集合=81体素).(2)未发现患者组有脑区白质FA值高于对照组.结论 早发精神分裂症患者存在胼胝体、扣带、前额叶和颞叶白质结构连接异常,可能与精神分裂症的发病机制有关.

Abstract：

Objective To investigate the changes of the brain structural connectivity in patients with early-onset schizophrenia (EOS, the onset of psychotic symptoms occurs before 18 years of age).Methods The subjects were 26 patients with EOS and 23 healthy controls (age, sex and years of received education were no significantly different from those of patients). Diffusion weighted images of the whole brains were acquired with a single-shot echo planar imaging (EPI) sequence aligned to the straight axial plane. After preprocessed with DTI-studio and Statistical Parametric Mapping-V (SPM5) software, the fractional anisotropy (FA) images of the two groups underwent two-sample t-test with the methods of voxel-based analysis (VBA) using SPM5 software package. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Results EOS patients had significantly reduced FA of white matter in the truncus corporis callosi (MNI: 3,16,23; cluser = 1003 voxels) , left temporal lobe (MNI:-28,28,30;cluser = 170 voxels) , left prefrontal lobe (MNI:-28,28,30; cluser = 99 voxels) and right prefrontal lobe (MNI:48,-10,54; cluser =81 voxels) , compared with the healthy controls. Conclusions There is structural disconnectivity of white matter in several brain regions. These abnormal changes may be involved in the neuropathology of schizophrenia.     

首发偏执型精神分裂症患者的脑白质磁共振弥散张量成像研究

目的探讨首发未用药的偏执型精神分裂症患者的多个脑区白质磁共振弥散张量成像(diffusion tensor imaging,DTI)的特点,以期为精神分裂症"脑内连接异常的假说"提供依据。方法选取20例首发偏执型精神分裂症患者,应用DTI扫描,检测脑内21个感兴趣区(regions of interest,ROI)白质纤维的微细结构,并与20名年龄、性别和文化程度相匹配的正常对照比较。结果患者组额叶、内囊前肢、外囊的左右两侧FA值和左侧颞叶、左侧内囊膝部、胼胝体膝部FA值小于对照组(P0.05)。患者组额叶左右侧FA值差异无统计学意义(P0.05),而对照组左侧大于右侧(P0.05);患者组内囊膝部和后肢FA值右侧大于左侧(P0.05),而对照组左侧大于右侧(P0.05)。患者组双侧外囊FA值均小于对照组(P0.05)。结论未用药首发偏执型精神分裂症患者脑内多个白质区部分各向异性降低,尤其是额叶皮层下环路更加显著,数个白质区部分各向异性的正常"左右"的偏侧性缺失或倒置,支持精神分裂症脑内连接异常的神经病理假说。     

精神分裂症患者全脑白质纤维弥散张量成像的初步研究

目的运用能够提示白质纤维(white matter,WM)完整性的弥散张量成像(diffusion tensor imaging,DTI)技术,探讨精神分裂症患者全脑白质纤维是否受到损害。方法对21例精神分裂症患者(患者组)和21名健康人(对照组)进行全脑DTI扫描,用SPM2(Statistical Parametric Maps,SPM)软件对图像进行处理,采用以像素为基础的分析方法(voxel-based analysis,VBA)对两组的分数各向异性(fractional anisotropy,FA)值进行组间比较。结果患者组下列脑区的FA值显著低于对照组(P<0·001):左侧额眶区和右侧额中回的白质、双侧颞下回白质、双侧顶叶内侧白质、右侧前扣带、双侧海马、双侧大脑脚、双侧岛叶、右侧放射冠和右侧小脑上脚。结论精神分裂症多个部位脑白质纤维的完整性受到破坏。     

有无冲动攻击行为首发精神分裂症脑灰质体积的比较

目的 比较有无冲动攻击行为精神分裂症脑灰质结构的不同.方法 收集16例有冲动攻击行为和24例无冲动攻击行为的首发未用药的精神分裂症患者,以三维快速扰相梯度回波序列获得其脑部磁共振成像.所得图像以统计参数图软件包进行预处理,然后两组脑局部灰质体积进行t检验.结果 有冲动攻击行为组右侧中央前回、中央后回区(MNI:x=44,y=-4,z=58;体素集合数=851)和右侧眶额回区(MNI:x=20,y=34,z:-24,体素集合数=108)脑灰质体积小于无冲动攻击行为组,差异有统计学意义(t=-3.72,P<0.001;t:3.17,P<0.001).未发现冲动攻击行为组存在灰质体积大于无冲动攻击行为组的脑区.结论 右侧中央前回、中央后回和眶额回灰质异常与精神分裂症的冲动攻击行为可能有关.     

未经治疗的抑郁症首次发病患者脑弥散张量成像的研究

目的 通过对未经治疗的抑郁症首次发病(以下简称首发)患者进行弥散张最成像(DTI)检查,探讨抑郁症患者脑门质的完整性及其与病程和抑郁严重程度的相关性.方法 对17名首发末服药抑郁症患者(以下简称患者组)和17名年龄、性别和文化程度相匹配的健康对照(以下简称对照组)进行全脑DTI扫描.以基于体素的分析比较两组受试者脑白质的分数各向异性(FA)的差异.提取差异有统计学意义的脑区的FA绝对值,将其与汉密尔顿抑郁量表(17项,HAMD)总分和患者病程进行相关分析.结果 患者组的双侧额中回、左侧扣带回和颞下回白质的FA值显著低于对照组(P＜0.01,cluster＞100).右侧额中回的FA值与病程呈显著负相关(r=-0.732,P=0.001).未发现各脑区的FA值与HAMD总分存在相关.结论脑白质完整性异常可能是抑郁症的生物学特征之一,抑郁症病程对脑白质的完整性有明显影响.     

精神分裂症早期的脑白质和灰质信号强度下降

目的分析精神分裂症早期阶段脑灰质和脑白质结构的变化。方法对25例早期阶段(病程小于6个月)的首发未用药的精神分裂症患者和28名正常对照的脑部进行磁共振T1加权成像,所得图像以统计参数图软件包进行预处理,再对两组脑灰质密度和白质信号强度进行t检验。结果患者组左侧岛叶区(x=34,y=18,z=-2,体素集合数=163)、左枕叶(x=14,y=-66,z=14,体素集合数=76)、右侧额叶(x=46,y=44,z=8,体素集合数=74)白质信号强度较正常对照组降低(t=-3.78,P=0.007;t=-3.36,P=0.02;t=3.26,P=0.03);右侧枕叶(x=10,y=-84,z=8,体素集合数=64)脑灰质信号强度比正常对照组降低(t=3.12,P=0.03)。结论精神分裂症早期阶段即存在脑实质结构异常,以白质为著。     

精神分裂症首次发病患者的磁共振弥散张量显像研究

目的探讨从未用过药的精神分裂症首次发病(以下简称首发)患者的重要白质及部分灰质区的磁共振弥散张量显像(DTI)的特点。方法选取9例首发精神分裂症患者(患者组)及9名年龄、性别、受教育程度与患者组相配对的健康者,应用DTI成像技术检测脑额颞交界处、内囊等白质区和颞中回灰质、中央前回、中央后回等灰质区的各向异性(FA)、表观扩散系数(ADC)及双侧海马体积。结果患者组及对照组组内左右两侧兴趣区FA值及ADC值的差异无统计学意义(P>0.05);患者组与对照组各感兴趣区FA值差异无统计学意义(P>0.05),但患者组颞中回灰质(8.655×10-9)、中央前回(7.816×10-9)、中央后回(7.855×10-9)ADC值高于对照组(分别为7.428×10-9,6.921×10-9,7.013×10-9;P=0.049,0.009,0.005);两组内及组间双侧海马体积比较,差异均无统计学意义(P>0.05)。结论首发精神分裂症患者与健康者DTI参数之间没有明显区别。     

精神分裂症首次发病患者的脑扩散张量成像研究

目的 利用磁共振扩散张量成像(DTI)技术研究未经药物治疗的精神分裂症首次发病(以下简称首发)患者主要脑区白质纤维束的异常.方法 选取26例首发精神分裂症患者(患者组)和20名健康志愿者(对照组)行脑DTI扫描(两组均为右利手),测量胼胝体膝部、压部、双侧额叶白质、扣带束前部及海马头的部分各向异性(FA)值.结果 (1)对照组左侧扣带束FA值(0.428±0.067)大于右侧(0.375±0.079;P＜0.05).(2)患者组两侧相对应感兴趣区FA值差异均无统计学意义(P＞0.05).(3)患者组左右侧胼胝体压部FA值(均为0.734±0.085)、左右侧扣带束前部FA值(0.300±0.068和0.306 4±0.062)均低于对照组(0.785±0.045,0.428±0.067,0.375±0.079;均P＜0.05).结论 首发精神分裂症患者存在双侧扣带束、胼胝体压部白质纤维束的受损,支持脑内连接异常假说.     

首发精神分裂症阳性症状为主型患者脑弥散张量成像研究

目的 探讨首发精神分裂症阳性症状为主型患者主要脑区白质纤维束有无异常.方法 对未系统使用过精神药物治疗的20例首发精神分裂症阳性症状为主型患者和20名正常对照进行磁共振弥散张量成像(DTI)扫描,测量胼胝体膝部、压部、双侧额叶白质、双侧扣带束前部和双侧海马头部分各向异性(FA)值.结果 ①患者组及对照组组内比较,左右侧FA值差异均无统计学意义(P>0.05).②患者组左侧海马头和胼胝体压部FA值[(0.17±0.03),(0.73±0.09)]显著低于对照组[(0.20±0.02),(0.79±0.05)],差异均有统计学意义(P<0.05);③患者组左右侧扣带束前部FA值[(0.28±0.06),(0.29±0.05)]低于对照组[(0.43±0.07),(0.38±0.08)],差异均有统计学意义(P<0.01).结论 首发精神分裂症阳性症状为主型患者双侧扣带束前部、胼胝体压部及左侧海马头的白质纤维束完整性受损,提示其可能存在脑神经发育连接异常.     

首次发病未用药老年抑郁症患者脑白质完整性的弥散张量成像研究

目的 使用弥散张量成像探讨首次发病未用药老年抑郁症患者的脑白质完整性.方法 15例首次发病未用药的老年抑郁症患者和15例正常对照组接受脑弥散张量成像扫描,用基于体素的分析方法对脑内所有体素的各向异性分数(FA)逐一进行组间比较.结果 与正常对照组相比,首次发病未用药老年抑郁症患者左侧前扣带(丛集体积=106体素,t=3.21)、右侧前扣带(丛集体积=60体素,t=2.71)、右侧膝下扣带(丛集体积=63体素,t=3.37)、左侧脑干(丛集体积=62体素,t=3.25)白质FA值显著降低(检验水准为未校正的单侧P＜0.01,体素集阈值＞50体素).结论 老年抑郁症发病早期存在双侧前扣带及右侧膝下扣带白质完整性下降,经由该脑区的神经通路损害可能与老年抑郁症的病理机制有关.     

White matter abnormalities in subjects at ultra high-risk for schizophrenia and first-episode schizophrenic patients

Schizophrenia is associated with neuroanatomical abnormalities. Gray matter decrease seems to predate first schizophrenic episode. Whether white matter abnormalities predate the onset of psychotic symptoms is unclear. We investigated this issue using voxel-based morphometry (VBM) of structural magnetic resonance images to examine individuals with prodromal symptoms who were at ultra high-risk (UHR) of developing schizophrenia and compared them to first-episode schizophrenic patients and healthy controls. White matter volume maps from high-resolution magnetic resonance T1 weighted whole brain images were analyzed in a cross-sectional study using SPM2 in 30 UHR patients, 23 first-episode schizophrenic patients and 29 healthy controls. UHR patients showed significant lower white matter volume in the right superior temporal lobe compared to healthy controls. First-episode patients with schizophrenia showed widespread smaller white matter volume bilaterally compared to UHR patients. This study provides first evidence for smaller white matter volume in the right temporal lobe of UHR patients, one of the key structures in the pathophysiology of schizophrenia. Furthermore, white matter abnormalities seem to progress after transition into schizophrenia.     

Abnormal asymmetry of white matter integrity in schizophrenia revealed by voxelwise diffusion tensor imaging

A number of magnetic resonance imaging (MRI) studies have revealed morphological cortical asymmetry in the normal human brain, and reduction or inversion of such hemispheric asymmetry has been reported in schizophrenia. On the other hand, diffusion tensor imaging (DTI) studies have reported inconsistent findings concerning abnormal asymmetry of white matter integrity in schizophrenia. Our aim was to confirm whether there is reduced or inverted asymmetry of white matter integrity in the whole brain in schizophrenia. For this study, 26 right-handed schizophrenia patients, and 32 matched healthy control subjects were investigated. Voxelwise analysis of DTI data was performed using the tract-based spatial statistics. The fractional anisotropy (FA) images were normalized and projected onto the symmetrical white matter skeleton, and the laterality index (LI) of FA, determined by 2 × (left - right)/(left + right), was calculated. The results reveal that schizophrenia patients and healthy controls showed similar patterns of overall FA asymmetries. In the group comparison, patients showed significant reduction of LI in the external capsule (EC), and posterior limb of the internal capsule (PLIC). The EC cluster revealed increased rightward asymmetry, and the PLIC cluster showed reduced leftward asymmetry. Rightward-shift of FA in the EC cluster correlated with negative symptom severity. Considering that the EC cluster includes the uncinate and inferior occipitofrontal fasciculi, which have connections to the orbitofrontal cortex, abnormal asymmetry of white matter integrity in schizophrenia may play a crucial role in the pathogenesis of schizophrenia, through the altered connectivity to the orbitofrontal cortex.     

Volumetric white matter abnormalities in first-episode schizophrenia: a longitudinal, tensor-based morphometry study

OBJECTIVE: While schizophrenia has long been considered a disorder of brain connectivity, few studies have investigated white matter abnormalities in patients with first-episode schizophrenia, and even fewer studies have investigated whether there is progressive white matter pathology in the disease. METHOD: The authors obtained a T1-weighted structural magnetic resonance imaging (MRI) scan on 41 patients with first-episode schizophrenia. These first-episode schizophrenia patients were analyzed relative to 47 age- and sex-matched healthy comparison subjects who also underwent an MRI scan. Of the baseline participants, 25 first-episode schizophrenia patients and 26 comparison subjects returned 2 to 3 years later for a follow-up scan. To identify regional volumetric white matter differences between the two groups at baseline, voxel-based morphometry in statistical parametric mapping-2 (SPM2) was used, while tensor-based morphometry was used to identify the longitudinal changes over the follow-up interval. RESULTS: The first-episode schizophrenia patients exhibited volumetric deficits in the white matter of the frontal and temporal lobes at baseline, as well as volumetric increases in the white matter of the frontoparietal junction bilaterally. Furthermore, these first-episode schizophrenia patients lost considerably more white matter over the follow-up interval relative to comparison subjects in the middle and inferior temporal cortex bilaterally. CONCLUSIONS: These results indicate that patients with schizophrenia exhibit white matter abnormalities at the time of their first presentation of psychotic symptoms to mental health services and that these abnormalities degenerate further over the initial years of illness. Given the role that white matter plays in neural communication, the authors suggest that these white matter abnormalities may be a cause of the dysfunctional neural connectivity that has been proposed to underlie the symptoms of schizophrenia.     

抑郁症患者脑白质变化初步研究

目的：利用能够提示脑白质纤维完整性的磁共振弥散张量成像（DTI）探讨首发和复发重性抑郁症患者脑白质纤维的变化及其差异。方法：20例重性抑郁症患者（首发9例，复发11例）和20名正常对照者均经常规磁共振成像（MRI）平扫，未发现异常者继续进行DTI和结构MRI（3D）扫描，基于像素的全脑分析技术对DTI数据进行分析。结果：与对照组相比较，抑郁症组白质纤维结构在双侧额中回、右顶下小叶及双侧脑岛等区域白质的各向异性值（FA）显著降低（各脑区P均〈0.001，cluster〉30像素）;与首发抑郁症患者相比较，复发抑郁症患者右侧额上回、右顶叶、中央前回、中央后回及右顶下小叶等区域FA值降低更为显著（各脑区P均〈0.001，cluster〉10像素）。结论：重性抑郁症患者存在脑白质异常，抑郁反复发作会导致脑白质损害进一步加重。     

Planum temporale and Heschl gyrus volume reduction in schizophrenia: a magnetic resonance imaging study of first-episode patients

BACKGROUND: Magnetic resonance imaging studies in schizophrenia have revealed abnormalities in temporal lobe structures, including the superior temporal gyrus. More specifically, abnormalities have been reported in the posterior superior temporal gyrus, which includes the Heschl gyrus and planum temporale, the latter being an important substrate for language. However, the specificity of the Heschl gyrus and planum temporale structural abnormalities to schizophrenia vs affective psychosis, and the possible confounding roles of chronic morbidity and neuroleptic treatment, remain unclear. METHODS: Magnetic resonance images were acquired using a 1.5-T magnet from 20 first-episode (at first hospitalization) patients with schizophrenia (mean age, 27.3 years), 24 first-episode patients with manic psychosis (mean age, 23.6 years), and 22 controls (mean age, 24.5 years). There was no significant difference in age for the 3 groups. All brain images were uniformly aligned and then reformatted and resampled to yield isotropic voxels. RESULTS: Gray matter volume of the left planum temporale differed among the 3 groups. The patients with schizophrenia had significantly smaller left planum temporale volume than controls (20.0%) and patients with mania (20.0%). Heschl gyrus gray matter volume (left and right) was also reduced in patients with schizophrenia compared with controls (13.1%) and patients with bipolar mania (16.8%). CONCLUSIONS: Compared with controls and patients with bipolar manic psychosis, patients with first-episode schizophrenia showed left planum temporale gray matter volume reduction and bilateral Heschl gyrus gray matter volume reduction. These findings are similar to those reported in patients with chronic schizophrenia and suggest that such abnormalities are present at first episode and are specific to schizophrenia.     

Effect of DAOA genetic variation on white matter alteration in corpus callosum in patients with first-episode schizophrenia

D-amino acid oxidase activator (DAOA) gene, which plays a crucial role in the process of glutamatergic transmission and mitochondrial function, is frequently linked with the liability for schizophrenia. We aimed to investigate whether the variation of DAOA rs2391191 is associated with alterations in white matter integrity of first-episode schizophrenia (FES) patients; and whether it influences the association between white matter integrity, cognitive function and clinical symptoms of schizophrenia. Forty-six patients with FES and forty-nine healthy controls underwent DTI and were genotyped for DAOA rs2391191. Psychopathological assessments were performed by Brief Psychiatric Rating Scale (BPRS) and Scale for Assessment of Negative Symptoms (SANS). Cognitive function was assessed by MATRICS Consensus Cognitive Battery (MCCB). Schizophrenia patients presented lower fractional anisotropy (FA) and higher radial diffusivity (RD), mainly spreading over the corpus callosum and corona radiata compared with healthy controls. Compared with patients carrying G allele, patients with AA showed lower FA in the body of corpus callosum, and higher RD in the genu of corpus callosum, right superior and anterior corona radiata, and left posterior corona radiata. In patients carrying G allele, FA in body of corpus callosum was positively correlated with working memory, RD in genu of corpus callosum was negatively associated with the speed of processing, working memory, and the composite score of MCCB, while no significant correlations were found in AA homozygotes. In our study, patients with FES presented abnormal white matter integrity in corpus callosum and corona radiata. Furthermore, this abnormality was associated with the genetic variation of DAOA rs2391191, with AA homozygotes showing less white matter integrity in the corpus callosum. Our findings possibly provide further support to the evidence that DAOA regulates the process of glutamatergic neurotransmission and mitochondrial function in the pathophysiological mechanism of schizophrenia.

     

Gray and white matter brain abnormalities in first-episode schizophrenia inferred from magnetization transfer imaging

BACKGROUND: Neuroimaging studies suggest that schizophrenia is associated with gray and possibly white matter changes. It is unclear whether these changes are present at illness onset or which brain structures are selectively affected. New imaging methods such as magnetization transfer imaging may be more sensitive than conventional volumetric imaging to the subtle structural brain changes in schizophrenia. METHODS: High-resolution volumetric T1-weighted images and magnetization transfer images were acquired from 30 patients (29 with first-episode schizophrenia and 1 with schizophreniform psychoses) and 30 control subjects. Images were processed using voxel-based morphometry, which allows whole-brain analysis. RESULTS: Compared with controls, the magnetization transfer ratio (an index of signal loss derived from magnetization transfer imaging) was reduced bilaterally in the medial prefrontal cortex (right greater than left), insula (left greater than right), and white matter incorporating the fasciculus uncinatus (left greater than right) in the patient group. Analysis of the T1-weighted images did not reveal significant volumetric differences between patients and controls. CONCLUSIONS: Gray and white matter abnormalities are present in schizophrenia at illness onset. The magnetization transfer ratio is sensitive to these abnormalities, which cannot be explained by detectable atrophy in our patient group.