Comparative study of regional homogeneity in schizophrenia and major depressive disorder

Compelling evidence suggests that there is a considerable overlap in structural and functional alternation in the brain between different neuropsychiatric disorders. However, whether these overlaps are specific for schizophrenia has yet to be investigated. A total of 36 patients with paranoid schizophrenia, 43 patients with major depressive disorder (MDD), and 44 healthy controls were recruited to undergo resting‐state functional magnetic resonance imaging (rs‐fMRI) for analysis of regional homogeneity (ReHo). Twelve regions of interest (ROIs) in the frontal and temporal lobes were generated and one‐way ANOVA was performed to test the ReHo differences within these ROIs between the above three groups. The ReHo values within ROIs were extracted to investigate whether a left‐right asymmetry existed in a mental disorder. One‐way ANOVA showed significant differences in ReHo in the right superior frontal gyrus and left superior temporal gyrus; post hoc analysis revealed that schizophrenic patients had lower ReHo in the left superior temporal gyrus than either control subjects or patients with MDD. Increased ReHo was observed in the right superior frontal gyrus in schizophrenic patients compared with control subjects, and a left‐less‐than‐right asymmetry was also found in this region in schizophrenic patients. The above alterations in ReHo were not affected by age and genders. Our study suggests that the altered ReHo in the superior frontal and temporal gyrus may be specific for schizophrenia rather than MDD. A left‐less‐than‐right asymmetry activation pattern may exist in the resting‐state superior frontal gyrus in schizophrenia. This finding would be helpful for better understanding the pathological mechanisms of schizophrenia. © 2012 Wiley Periodicals, Inc.     

Differential frontal activation in schizophrenia and bipolar illness during verbal fluency

INTRODUCTION: The precise nature of frontal lobe dysfunction in schizophrenia remains unclear. We have previously demonstrated, using fMRI, a task-specific attenuation of frontal activation in schizophrenic patients. By using an identical methodology in matched bipolar subjects, we sought to determine whether this finding is specific to schizophrenia or a correlate of psychosis in general. METHOD: Five dextral male bipolar patients and matching groups of schizophrenic subjects and controls were studied using fMRI. Echoplanar images were acquired while subjects performed two paced tasks: covert verbal fluency and a semantic decision task. Generic brain activation maps were constructed from individual images by sinusoidal regression analysis. Between-group differences in the mean power of experimental response were identified on a voxel-wise basis by an analysis of variance (ANOVA). RESULTS: The bipolar patients showed extensive prefrontal activation during verbal fluency which was significantly greater than in controls. There was no difference in the prefrontal BOLD response during the semantic decision task. CONCLUSIONS: These data indicate that bipolar patients show a strikingly different pattern of frontal responses compared to those with schizophrenia and provide further evidence that abnormal frontal activation in psychotic disorders is more apparent during verbal fluency than semantic decision.     

Functional Magnetic Resonance Imaging of Motor Cortex Activation in Schizophrenia

Previous fMRI studies of sensorimotor activation in schizophrenia have found in some cases hypoactivity, no difference, or hyperactivity when comparing patients with controls; similar disagreement exists in studies of motor laterality. In this multi-site fMRI study of a sensorimotor task in individuals with chronic schizophrenia and matched healthy controls, subjects responded with a right-handed finger press to an irregularly flashing visual checker board. The analysis includes eighty-five subjects with schizophrenia diagnosed according to the DSM-IV criteria and eighty-six healthy volunteer subjects. Voxel-wise statistical parametric maps were generated for each subject and analyzed for group differences; the percent Blood Oxygenation Level Dependent (BOLD) signal changes were also calculated over predefined anatomical regions of the primary sensory, motor, and visual cortex. Both healthy controls and subjects with schizophrenia showed strongly lateralized activation in the precentral gyrus, inferior frontal gyrus, and inferior parietal lobule, and strong activations in the visual cortex. There were no significant differences between subjects with schizophrenia and controls in this multi-site fMRI study. Furthermore, there was no significant difference in laterality found between healthy controls and schizophrenic subjects. This study can serve as a baseline measurement of schizophrenic dysfunction in other cognitive processes.

Graphical Abstract

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精神分裂症白质损害与发病年龄的弥散张量成像研究

目的:应用弥散张量成像(DTI)比较精神分裂症患者脑白质与正常人群间的差异,并探究各向异性比值(FA)的改变与发病年龄之间的相关性。方法:纳入27例精神分裂症患者和29名性别、年龄及受教育程度相匹配的健康对照。两组研究对象均接受头颅磁共振检测。患者组按照发病年龄分为早发组(发病年龄18岁)和成年发病组(发病年龄≥18岁)。采用基于体素的分析方法,分别比较患者组和对照组、早发组和成年发病组之间FA值的差异,并在控制性别、病程和药物剂量影响的前提下,分析FA值与患者发病年龄的相关性。结果:与健康对照比较,患者组在右侧上纵束、右侧放射冠上部的FA值降低;患者组中早发组和成年发病组间FA值的差异无显著性。患者组FA值与发病年龄呈正相关的脑区包括右侧放射冠前部(r=0.70,P0.01)、右侧胼胝体膝部(r=0.65,P0.01);未发现呈负相关的脑区。结论:本研究提示精神分裂症患者右侧脑区上纵束及放射冠部位存在白质损害,发病年龄愈早,右侧放射冠及胼胝体膝部白质纤维的受损愈重。这对精神分裂症病理生理改变及脑结构异常的进一步研究具有提示作用。     

Quantitative proton magnetic resonance spectroscopy of the bilateral frontal lobes in patients with bipolar disorder.

BACKGROUND: Using 31P and 1H magnetic resonance spectroscopy (MRS) we previously reported that phosphocreatine was decreased in the left frontal lobe and choline-containing compounds were increased in the basal ganglia in the depressive state in patients with bipolar disorder. We applied quantitative 1H-MRS for further characterization of biochemical alteration in the frontal lobes of bipolar patients. METHODS: Twenty-three bipolar patients and 20 normal controls were examined by 1H-MRS with a 1.5T MR system. All patients were examined in the euthymic state, and eight patients were also examined in the depressive state. Volumes of interest of 2.5 x 2.5 x 2.5 cm were selected in the left and right frontal lobes. Absolute concentrations of N-acetyl-1-aspartate, creatine plus phosphocreatine, and choline-containing compounds were calculated from each metabolite peak. RESULTS: Creatine concentration in the left frontal lobe in bipolar patients in the depressive state was significantly lower than that in the euthymic state. Creatine concentration in the right frontal lobe in the male patients was significantly higher than that in the female patients and a similar trend was also found in the control subjects. CONCLUSIONS: We found a state-dependent change of creatine metabolism in the left frontal lobe of bipolar patients. The present results are compatible with our previous report of decreased phosphocreatine measured by 31P-MRS in the left frontal lobe in bipolar disorder. We also found an effect of gender on the creatine concentration. There may be a gender difference in creatine transport function into the brain.     

单胺氧化酶A基因多态性与精神分裂症的关联研究

目的探讨河南地区汉族人群单胺氧化酶A（monoamine oxidase A，MAOA）基因多态性与精神分裂症的关系。方法参照CCMD-3诊断标准，选取212例精神分裂症患者与168名正常对照，应用聚合酶链反应及限制性片段长度多态性技术检测MAOA基因多态性，采用病例一对照的关联分析方法对精神分裂症患者及正常对照的基因型和等位基因频率进行分析。结果（1）MAOA基因的基因型在患者组和对照组中均符合Hardy-Weinberg平衡定律（X^2=0．618，dr：2，P〉0、05；X^2=3．173，df=2，P〉0．05）。（2）MAOA基因的基因型和等位基因频率在患者组与对照组间的分布差异无统计学意义（P〉0．05）。（3）按性别分组，男性患者组中CT基因型分布频率显著高于男性对照组（X^2=7．654，P=0．022）。（4）MAOA基因的基因型和等位基因频率在家族史阴、阳性间的分布差异无统计学意义（P〉0．05）。结论没有发现MAOA基因多态性与汉族精神分裂症的发病有关联，但对性别发病有影响，基因型CT可能是男性精神分裂症发病的易感因素。     

老年精神分裂症和Alzheimer氏病患者认知功能的对照研究

目的：探讨老年精神分裂症和Alzheimer氏病在额叶执行功能和记忆方面的神经心理功能障碍及其特征;了解老年精神分裂症和Alzheimer氏病人认知功能与社会生活功能的关系。方法：采用简易智力状态检查（MMSE）、韦氏记忆量表（WMS）、威斯康星卡片分类测验（WCST）、日常生活能力量表（Alzheimer氏病）,对34例45岁（含45岁）以前起病反复发作或持续到老年的精神分裂症、28例Alzheimer氏病及31例正常对照组进行对照研究。结果：老年精神分裂症和Alzheimer氏病都有记忆障碍和额叶执行功能障碍。老年精神分型症语义记忆受损严重程度与Alzhe-imer氏病无明显差异,而对新信息在延迟期的快速遗忘损害要轻;老年精神分裂症的额叶执行功能障碍对记忆损有选择性,两者密切相关,Alzheimer氏病的记忆损害与额叶执行功能障碍的相关不明显。老年精神分裂症的社会日常生活功能优于Alzheimer氏病,与正常老年人无明显差异。结论：老年精神分裂症认知功能损害不同于Alzhe-imer氏病,有一定的特征性。提示老年精神分裂症和Alzheimer氏病认知功能障碍的差别在于各自神经生物学病理机制的不同。     

Corpus callosum in first-episode patients with schizophrenia--a magnetic resonance imaging study

BACKGROUND: Morphometric studies on the corpus callosum (CC) in schizophrenia have yielded contradictory results. The aim of the present study was to investigate magnetic resonance imaging (MRI) abnormalities of the CC in first-episode patients with schizophrenic psychoses. METHOD: We assessed volumetric MRI in 31 patients with diagnoses of schizophrenia, schizophreniform or schizoaffective disorder (DSM-IV) and a maximum exposure to neuroleptics of 2 weeks. As a control group, 12 healthy age- and sex-matched individuals were included in the study. A whole body scanner at 1.5 Tesla was used to obtain 3D T1- and T2-weighted MR datasets. The data were evaluated semi-automatically (intracranial volume, total brain volume) and manually (CC) with the software NMRwin. RESULTS: Patients had smaller CC and CC subdivisions than controls. Schizophrenic and unaffected women exhibited larger total CC and rostral subdivisions than men in both groups. Handedness did not exert an influence. CONCLUSIONS: Our findings are in line with other in vivo morphometric studies on the CC in schizophrenia. The larger CC area in women may reflect general gender-related differences in CC size as described in healthy individuals.     

Abnormalities of auditory P300 cortical current density in patients with schizophrenia using high density recording.

While P300 current density analysis has been performed in schizophrenic patients, the event-related potential data have never been obtained using a high density recording, nor have their cortical images been well demonstrated. In this study, the auditory P300 elicited by an oddball paradigm was recorded using a high density recording system of 128 channels. Thirteen male patients who met DSM-IV criteria for schizophrenia were compared with 20 healthy male controls. The cortical current density analysis of low resolution electromagnetic tomography (LORETA) was applied to the P300 component, and this resulted in the values of 6222 current density points over the surface of a cortex model. The inter-group difference of P300 current density was assessed using a point-by-point comparison by t-test. While the normal controls demonstrated the cortical activation of bilateral frontal, temporal and parietal cortex during the oddball paradigm, visual inspection suggested that in the schizophrenic patients these areas were less activated. The inter-group significance of P300 current density was dominant over the left hemisphere, and particularly over the left prefrontal area. It is concluded that the LORETA current density analysis localizes the neural activity from the cortical fronto-temporo-parietal network as the neural substrates of the scalp recorded P300. The dysfunction of such a network, especially over the left hemisphere, possibly subserves the scalp recorded P300 abnormality in schizophrenia.     

Association study of neuregulin 1 gene polymorphisms with auditory P300 in schizophrenia

Neuregulin 1 (NRG1), a gene involved with myelin production has been shown to have a positive correlation with schizophrenia. Event-related potentials (ERPs) studies provide the evidence of disturbed electrophysiologic marker in schizophrenia. The present study investigated the association of NRG1 genotypes with P300 in schizophrenia. Three polymorphisms in NRG1 gene were detected in 287 Chinese Han schizophrenics and 120 healthy control subjects. Among the total sample, 140 patients and 96 controls underwent P300. There were no significant differences for genotype distributions and allele frequencies between schizophrenic group and the control. A significant difference was observed between the schizophrenic patients and controls in the AT haplotype, with Odds Ratio 0.304 (P = 0.000882, 95% CI = 0.145-0.636). P300 amplitude in the schizophrenic group was significantly lower than that of the controls at Fz, Cz, Pz. P300 latency in the schizophrenic group was also significantly longer than that of the controls at Cz, Pz, Fz. Significant differences of P300 latency between three genotypes of rs3924999 were found at Cz and Pz both in schizophrenic group and the controls. The G/G carriers of rs3924999 tended to perform worse in the P300 latency as compared to A/A or A/G carriers both in the schizophrenia and controls. There were no significant differences for P300 latency and amplitude between schizophrenic group and controls for AT haplotype. NRG1 gene is a susceptible gene for Chinese Han schizophrenia and AT haplotype might have the protective role in the schizophrenia. Rs3924999 in NRG1 gene might functionally impact cognitive processing.     

Increased event-related potential latency and amplitude variability in schizophrenia detected through wavelet-based single trial analysis.

Analysis of single-trial event-related potentials can potentially yield important information about the underlying brain dynamics. We were specifically interested in latency and amplitude variability of the P3 component in patients with schizophrenia. For this purpose we developed a method for analyzing single-trial ERPs based on a wavelet smoothing algorithm, which is presented in detail. This method was applied to data from schizophrenic patients and healthy controls in an auditory Go/Nogo task. We found a significant increase of latency variability in the schizophrenic group at electrode Fz (frontal midline) and increased amplitude variability at electrode Pz (parietal midline). These results support the concept of increased cortical noise in patients with schizophrenia.     

Increased event-related potential latency and amplitude variability in schizophrenia detected through wavelet-based single trial analysis

Analysis of single-trial event-related potentials can potentially yield important information about the underlying brain dynamics. We were specifically interested in latency and amplitude variability of the P3 component in patients with schizophrenia. For this purpose we developed a method for analyzing single-trial ERPs based on a wavelet smoothing algorithm, which is presented in detail. This method was applied to data from schizophrenic patients and healthy controls in an auditory Go/Nogo task. We found a significant increase of latency variability in the schizophrenic group at electrode Fz (frontal midline) and increased amplitude variability at electrode Pz (parietal midline). These results support the concept of increased cortical noise in patients with schizophrenia.     

精神分裂症患者固有网络的功能磁共振成像的研究

目的:用功能磁共振成像(fMRI)检测精神分裂症患者静息状态固有网络功能连接方面的差异,探讨疾病特异性的生物学标记,为理解疾病机理发病机制和临床诊断提供新线索和依据.方法:对25例精神分裂症患者、25例健康同胞和25例健康对照进行静息状态的fMRI资料采集.结果:精神分裂症患者、健康同胞和健康对照共同的固有网络内两两脑区之间的功能连接比较发现有三条异常功能连接:左侧前额叶背外侧(DLPFC)与右侧额下回(IFG)之间的功能连接,左侧颞下回(ITG)与扣带回后部皮质/楔前叶(PCC/PCu)之间的功能连接,双侧ITG之间的功能连接;LSD法发现,在任务负激活网络(TNN),精神分裂症患者和健康同胞均存在双侧ITG的功能连接升高,而仅精神分裂症患者存在PCC/PCu和左侧ITG的功能连接升高;在任务正激活网络(TPN),仅精神分裂症患者存在左侧DLPFC和右侧IFG的功能连接升高.未发现分属TPN和TNN的两两脑区之间的功能连接差异.结论:精神分裂症患者及其健康同胞均存在固有网络的功能连接升高.精神分裂症的病理生理基础与TNN和TPN的功能连接增强有关.TNN的功能连接升高提示患精神分裂症的风险升高,并与精神分裂症的遗传易感性相关.     

Dopamine D4 receptor variants in chinese sporadic and familial schizophrenics

Variation in the number of tandem repeats of a 48 base pair (bp) unit was found in the gene of the dopamine D4 receptor (DRD4). The number of repetitions of the 48bp unit was shown to influence the binding of clozapine, which suggests that different alleles may function differently in vivo and affect the pathogenesis of schizophrenia. Genotypes of DRD4 polymorphism were analyzed for 47 schizophrenic probands who had at least one living sibling with a diagnosis of schizophrenia, 35 unaffected siblings of the schizophrenic proband, 42 sporadic schizophrenic patients, and 43 healthy controls without a family history of psychosis. There was no significant difference in genotypic or allelic distributions among the four groups. Significant differences in the frequencies of two- and seven-repeats alleles between the Chinese and Caucasians controls were noted. The present study did not support that a particular allele or genotype of the 48bp-repeat of DRD4 was associated with schizophrenia. Am. J. Med. Genet. 74:412–415, 1997. © 1997 Wiley-Liss, Inc.     

Apolipoprotein E genotype in Korean schizophrenic patients.

The apolipoprotein E (APOE) epsilon4 allele is a known risk factor for the development of Alzheimer's disease, however, an association of the APOE genotype with schizophrenia is controversial. We investigated the association in 60 Korean schizophrenic patients and 60 healthy controls. APOE genotypes were identified by reverse hybridization-based line probe assay. There were significant differences in the distribution of APOE genotypes between schizophrenic patients and controls. APOE epsilon2 and epsilon3 allele frequencies in schizophrenic patients were significantly different from those in controls. Our results suggest that APOE alleles seem to be operative in the pathogenesis of schizophrenic disorders.     

Decreased frontal lobe ratio of N-acetyl aspartate to choline in familial schizophrenia: a proton magnetic resonance spectroscopy study

Neuropathological and neuroimaging studies suggest neuronal dysfunction in schizophrenia. N-acetyl aspartate (NAA) is a useful marker of neuronal dysfunction that can be measured with magnetic resonance spectroscopy (MRS). In the present study NAA, choline (Cho), phospho-creatine ((P)Cr), inositol containing compounds and glutamine/glutamate (Glx) were assessed in the left frontal lobe and basal ganglia of subjects with familial schizophrenia, family members with mixed psychiatric diagnoses, unaffected family members, and community controls. Concentrations of metabolites were analyzed and expressed as ratios. NAA/Cho, NAA/(P)Cr and Glx containing compounds showed a negative correlation with age in the frontal lobe. After covarying for age, subjects with schizophrenia had a significant reduction in the left frontal lobe NAA/Cho ratio compared with unaffected family members (P=0.018) as well as with community non-familial (P=0.037) controls. These MRS observations support the hypothesis of a disease-related neuronal deficit in the frontal lobe of schizophrenic patients, and relatively normal basal ganglia.     

男性攻击性精神分裂症患者杏仁核功能连接的磁共振研究

目的:探讨男性攻击性精神分裂症患者是否存在杏仁核与其他脑区功能连接的异常.方法:对有攻击行为和没有攻击行为的男性精神分裂症患者各13例进行静息状态下功能磁共振成像.结果:与非攻击组相比,攻击组双侧额中回、右侧额上回、右侧脑岛、右侧顶上小叶、右侧扣带回等脑区与左侧杏仁核功能连接增强;双侧额上回、额中回、双侧颞上回、右侧颢中回等脑区与右侧杏仁核功能增强.结论:杏仁核与多个脑区之间特别是与额上回、额中回的功能连接增强可能与男性精神分裂症患者的攻击行为有关.     

首发精神分裂症患者脑磁共振质子波谱的对照研究

目的研究首发精神分裂症患者脑磁共振质子波谱(1HMRS)的变化。方法对26例首发精神分裂症患者和12例正常人分别进行MRI常规扫描和1HMRS检查,1HMRS采用定点分辨率波谱序列(TR2000毫秒,TE135毫秒),所测定的代谢产物包括N-乙酰基天门冬氨酸(NAA)、肌酸复合物(Cr)、胆碱复合物(Cho)、肌醇(MI)、乳酸(Lac)、谷氨酸及谷氨酰胺(Glu-Gln)。结果精神分裂症患者前额叶背外侧回中NAA/Cr值和NAA/Cho值显著低于对照组前额叶背外侧回(1.83±0.15/2.42±0.13,t=3.202,P<0.01,2.37±0.16/2.06±0.24,t=2.453,P<0.05);患者组海马区中NAA/Cr值(1.65±0.19)和NAA/Cho值(1.12±0.21)显著低于对照组海马中的NAA/Cr值(1.83±0.27,t=2.532,P<0.05)和NAA/Cho值(1.34±0.12,t=2.641,P<0.05);且NAA/Cr的水平与简明精神障碍评定量表阴性症状总分呈负相关(r=-0.416,P<0.05);而丘脑、颞叶颞横回、枕叶脑区的NAA/Cr和NAA/Cho两组无显著性差异(P>0.05)。结论精神分裂症患者的1HMRS与正常人存在显著差异,提示精神分裂症存在神经元功能的异常,其前额叶背外侧回和海马两处脑区功能低下。     

A controlled study of 99mTc-HMPAO single-photon emission imaging in chronic schizophrenia.

Regional cerebral blood flow (rCBF) during a word fluency task was compared in twenty-five male, right-handed, medicated schizophrenic patients and twenty-five age-matched male, right-handed healthy volunteers, using 99mtechnetium-HMPAO multidetector single-photon emission tomography. Increased rCBF in caudate and thalamus was found in patients, probably secondary to neuroleptic medication. Patients showed decreased rCBF in left frontal cortical regions and increased rCBF in left posterior cortical regions, compared to controls. Patterns of left-sided frontal rCBF dominance in controls were reversed in patients, as were normal patterns of right-sided parietal rCBF dominance. Negative symptom score correlated inversely with mesial frontal rCBF, particularly on the left.     

Effect of SOX10 gene polymorphism on early onset schizophrenia in Chinese Han population

Schizophrenia is one of highly heritable psychiatric disorders. Patients with early onset schizophrenia tend to have a greater genetic loading and may be an attractive subpopulation for genetics studies. A single nucleotide polymorphism (SNP) rs139887 in sex-determining region Y-box 10 (SOX10), a candidate gene for schizophrenia, was suggested to be associated with schizophrenia although inconsistent results had been reported. The aim of this study was to evaluate the association between SOX10 rs139887 polymorphism and schizophrenia using an early onset sample in the Chinese Han population. A total of 321 schizophrenic patients with onset before age 18 and 400 healthy controls were recruited for association study. In addition, two populations involved in three studies were selected for meta-analysis to determine the effect of rs139887 on schizophrenia. Our association study results showed that the allele and genotype frequencies were significantly different between schizophrenic patients and controls (P=0.013 and P=0.034, respectively). Interestingly, a significant association in allele and genotype frequencies were found in male patients (P=0.017 and P=0.045, respectively), but not female patients. Moreover, the C/C genotype had a significant association with an earlier age of onset in male schizophrenic patients (Kaplan-Meier log-rank test P=0.029), but not in female patients (Kaplan-Meier log-rank test P=0.876). The meta-analysis result showed the same C allele was significantly associated with schizophrenia (P=0.007). In conclusion, the SOX10 rs139887 polymorphism was related to the development of schizophrenia in a gender-specific manner, and may be a significant genetic marker for managing subgroups and etiological clues in schizophrenia.