White matter integrity of the whole brain is disrupted in first-episode remitted geriatric depression

Previous studies have demonstrated lower-diffusion anisotropy within white matter in late-onset depression measured by diffusion tensor imaging, which provides information about brain white matter integrity. We have examined whether white matter is abnormal in first-episode remitted geriatric depression by using diffusion tensor imaging. Sixteen remitted geriatric depression patients and 14 well matched healthy controls underwent diffusion tensor-imaging scans of magnetic resonance imaging, which were analyzed by a rigorous voxel-based approach. We found that fractional anisotropy in white matter was lower in patients than in controls at the right superior frontal gyrus, left inferior frontal gyrus, left middle temporal gyrus, right inferior parietal lobule, right middle occipital gyrus, left lingual gyrus, right putamen and right caudate. These results suggested that the white matter integrity of the whole brain was disrupted in first-episode remitted geriatric depression, and that these abnormalities were perhaps involved in the psychopathology and pathophysiology of cognitive impairment in remitted geriatric depression.     

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。     

Compromised white matter tract integrity in schizophrenia inferred from diffusion tensor imaging

BACKGROUND: Current investigations suggest that brain white matter may be qualitatively altered in schizophrenia even in the face of normal white matter volume. Diffusion tensor imaging provides a new approach for quantifying the directional coherence and possibly connectivity of white matter fibers in vivo. METHODS: Ten men who were veterans of the US Armed Forces and met the DSM-IV criteria for schizophrenia and 10 healthy, age-matched control men were scanned using magnetic resonance diffusion tensor imaging and magnetic resonance structural imaging. RESULTS: Relative to controls, the patients with schizophrenia exhibited lower anisotropy in white matter, despite absence of a white matter volume deficit. In contrast to the white matter pattern, gray matter anisotropy did not distinguish the groups, even though the patients with schizophrenia had a significant gray matter volume deficit. The abnormal white matter anisotropy in patients with schizophrenia was present in both hemispheres and was widespread, extending from the frontal to occipital brain regions. CONCLUSIONS: Despite the small sample size, diffusion tensor imaging was powerful enough to yield significant group differences, indicating widespread alteration in brain white matter integrity but not necessarily white matter volume in schizophrenia.     

White matter abnormalities in first-episode schizophrenia or schizoaffective disorder: a diffusion tensor imaging study

OBJECTIVE: The goal of this study was to investigate brain white matter abnormalities by using diffusion tensor imaging in patients with schizophrenia or schizoaffective disorder close to illness onset. METHOD: Ten patients experiencing a first episode of schizophrenia or schizoaffective disorder and 13 healthy volunteers received diffusion tensor imaging and structural magnetic resonance imaging examinations. Voxel-wise analysis was used to compare fractional anisotropy maps in the white matter of the two groups following intersubject registration to Talairach space. RESULTS: Compared with healthy volunteers, patients demonstrated lower fractional anisotropy in the left internal capsule and left-hemisphere white matter of the middle frontal gyrus and posterior superior temporal gyrus. There were no areas of significantly higher fractional anisotropy in patients compared with healthy volunteers. CONCLUSIONS: These findings suggest that white matter pathology is present early in the course of schizophrenia and may be less pronounced than has been found in previous diffusion tensor imaging studies of patients with chronic illness. Further, these data are consistent with hypotheses regarding frontotemporal dysfunction and the failure of left-hemisphere lateralization in the pathophysiology of schizophrenia.     

Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study.

Evidence suggests that a disruption in limbic system network integrity and, in particular, the cingulate gyrus (CG), may play a role in the pathophysiology of schizophrenia; however, the cingulum bundle (CB), the white matter tract furnishing both input and output to CG, and the most prominent white matter fiber tract in the limbic system, has not been evaluated in schizophrenia using the new technology of diffusion tensor imaging (DTI).We used line scan DTI to evaluate diffusion in the CB in 16 male schizophrenia patients and 18 male control subjects, group-matched for age, parental socioeconomic status, and handedness. We acquired 4-mm-thick coronal slices through the entire brain. Maps of fractional anisotropy (FA) were generated to quantify diffusion within the left and right CB on eight slices that included the central portion of the CB.Results showed group differences, bilaterally, in area and mean FA for CB, where patients showed smaller area and less anisotropy than controls. For patients, decreased left CB correlated significantly with attention and working memory measures as assessed by the Wisconsin Card Sorting Test.These data provide strong evidence for CB disruptions in schizophrenia, which may be related to disease-related attention and working memory abnormalities.     

老年抑郁症恢复期患者认知损害与全脑白质纤维完整性的相关性研究

目的 探讨恢复期老年抑郁症患者全脑白质纤维完整性是否受损,并进一步分析其与认知损害是否关联.方法 对16例恢复期老年抑郁症患者(患者组)和14名健康老年人(对照组)进行汉密尔顿抑郁量表(HAMD)、简易智力状态检查(MMSE)和神经心理学评估后,行全脑弥散张量成像扫描,用SPM2软件处理图像,采用基于体素的分析方法进行组间比较分数各向异性(FA)值.结果 (1)HAMD、MMSE评分和神经心理学测试:患者组HAMD和MMSE评分与正常对照组的差异无统计学意义(P>0.05),但在听觉言语测验[(5.9±2.6)分]、连线测验A[(146±127)s]和B[(264±196)s]成绩均差于正常对照组[分别为(9.3±1.6)分,(73±25)s和(121±35)s;P<0.01～0.05].(2)FA值:患者组低于对照组的脑区主要包括:右侧额上回、左侧额下回、左侧颞中回、右侧顶下回、右侧枕中回、左侧舌回、右侧壳核和右侧尾状核(未校正,P<0.001).(3)患者组右侧额上回FA值与连线B测验成绩呈显著负相关(r=-0.556,P=0.049).结论 恢复期老年抑郁症患者多部位脑白质纤维的完整性受损,这可能是该类患者认知损害的神经病理基础.     

White matter abnormalities in first-episode, treatment-naive young adults with major depressive disorder

OBJECTIVE: The aim of this study was to explore the microstructural integrity of whole-brain white matter by diffusion tensor imaging in first-episode, treatment-naive young adults with major depressive disorder. METHOD: Diffusion tensor imaging scans were obtained from 14 first-episode, treatment-naive young adult patients with major depressive disorder and 14 healthy comparison subjects. A voxel-based method was used to analyze the scans. RESULTS: The patient group exhibited significantly lower fractional anisotropy values than healthy comparison subjects in the white matter of the right middle frontal gyrus, the left lateral occipitotemporal gyrus, and the subgyral and angular gyri of the right parietal lobe. There were no regions of significantly higher fractional anisotropy values in patients compared with healthy comparison subjects. CONCLUSIONS: These findings suggest that abnormalities of brain white matter may be present early in the course of major depressive disorder. They also support the idea that white matter lesions may disrupt the neural circuits involved in mood regulation and thus contribute to the neuropathology of major depressive disorder.     

Reduced white matter fractional anisotropy and clinical symptoms in schizophrenia: a voxel-based diffusion tensor imaging study

Although not consistently replicated, diffusion tensor imaging (DTI) studies in schizophrenia have revealed lower fractional anisotropy (FA) in various white matter regions, a finding consistent with the disruption of white matter integrity. In this study, we used voxel-based DTI to investigate possible whole-brain differences in the white matter FA values between 58 schizophrenia patients and 58 healthy controls. We also explored the association between FA values and clinical symptoms in schizophrenia. Compared with the controls, the schizophrenia patients showed significant FA reductions in bilateral superior longitudinal fasciculus, bilateral inferior fronto-occipital fasciculus, and genu of right internal capsule. Furthermore, in the patient group, the FA value of the anterior part of the corpus callosum was negatively correlated with the avolition score on the Scale for the Assessment of Negative Symptoms. These findings suggest widespread disruption of white matter integrity in schizophrenia, which could partly explain the severity of negative symptomatology.     

Reduced hippocampal anisotropy related to anteriorization of alpha EEG in schizophrenia

Dysfunctions of the hippocampus have been suggested to be related to schizophrenia, and reduced connectivity with other brain regions may be a key for the pathophysiology. The aim of this study was to investigate the effect of white matter anomalies in the hippocampus, as a sign of altered connectivity, on the brain electrical activity. We investigated seven first episode schizophrenic patients and seven age, gender and education-matched controls with diffusion tensor imaging and resting EEG. Fractional anisotropy was computed based on diffusion tensor imaging data for the right and left hippocampus for both groups. No group differences were found in hippocampal fractional anisotropy, EEG spectral power and topography. However a significant correlation was found between more anterior alpha activity and lower fractional anisotropy of both hippocampi in schizophrenics, but not in controls. More anterior alpha activity has been described in schizophrenia. We conclude that this feature might depict a group of schizophrenic patients with reduced hippocampal connectivity.     

Application of diffusion tensor imaging for detecting structural changes in the brain of schizophrenic patients

Abstract

Objective. Schizophrenia is a severe psychiatric illness. Although magnetic resonance imaging has been widely used for detecting brain structural and functional abnormalities in patients with schizophrenia, the findings are highly inconsistent between reports. This study investigates structural changes in the brains of schizophrenic patients. Methods. The brains of fifty male adults with schizophrenia and fifty age- and gender-matched healthy controls were scanned by diffusion tensor imaging. The differences in fractional anisotropy （FA） values between schizophrenic patients and healthy controls were analyzed. Results. Schizophrenic patients exhibited significantly decreased FA values in the right middle frontal gyrus, right inferior frontal gyrus, right superior temporal gyrus, left sub-temporal gyrus, left middle temporal gyrus, left cingulate gyrus, and left precentral gyrus compared with the control group. We did not find any brain regions with higher FA values in the patient group than in the control group. Conclusion. This study suggested that structural abnormalities in the frontal region of gray matter and white matter are present at the same time in patients with schizophrenia.     

Abnormal anterior cingulum in patients with schizophrenia: a diffusion tensor imaging study

Diffusion tensor imaging (DTI) can non-invasively examine the molecular diffusion of water in vivo and directly reflects the anatomical integrity of neural fibers in white matter. Fractional anisotropy (FA) can be calculated from DTI data, and utilized to evaluate white matter integrity. DTI was performed on 30 patients with schizophrenia and 19 healthy controls, and their FA values were subsequently measured in multiple brain regions. Statistical analyses revealed that FA values were decreased in the anterior cingulum of schizophrenia subjects. There were no significant differences between patients and controls in any other regions. This study supports the hypothesis that schizophrenia is associated with abnormal white matter integrity of the anterior cingulum.     

Uncinate fasciculus findings in schizophrenia: a magnetic resonance diffusion tensor imaging study

OBJECTIVE: Disruptions in connectivity between the frontal and temporal lobes may explain some of the symptoms observed in schizophrenia. Conventional magnetic resonance imaging (MRI) studies, however, have not shown compelling evidence for white matter abnormalities, because white matter fiber tracts cannot be visualized by conventional MRI. Diffusion tensor imaging is a relatively new technique that can detect subtle white matter abnormalities in vivo by assessing the degree to which directionally organized fibers have lost their normal integrity. The first three diffusion tensor imaging studies in schizophrenia showed lower anisotropic diffusion, relative to comparison subjects, in whole-brain white matter, prefrontal and temporal white matter, and the corpus callosum, respectively. Here the authors focus on fiber tracts forming temporal-frontal connections. METHOD: Anisotropic diffusion was assessed in the uncinate fasciculus, the most prominent white matter tract connecting temporal and frontal brain regions, in 15 patients with chronic schizophrenia and 18 normal comparison subjects. A 1.5-T GE Echospeed system was used to acquire 4-mm-thick coronal line-scan diffusion tensor images. Maps of the fractional anisotropy were generated to quantify the water diffusion within the uncinate fasciculus. RESULTS: Findings revealed a group-by-side interaction for fractional anisotropy and for uncinate fasciculus area, derived from automatic segmentation. The patients with schizophrenia showed a lack of normal left-greater-than-right asymmetry seen in the comparison subjects. CONCLUSIONS: These findings demonstrate the importance of investigating white matter tracts in vivo in schizophrenia and support the hypothesis of a disruption in the normal pattern of connectivity between temporal and frontal brain regions in schizophrenia.     

White matter abnormalities in early-onset schizophrenia: a voxel-based diffusion tensor imaging study

OBJECTIVE: To investigate abnormalities in the structural integrity of brain white matter as suggested by diffusion tensor imaging in adolescents with early-onset schizophrenia (onset of psychosis by age 18). METHOD: Twenty-six patients with schizophrenia and 34 age- and gender-matched healthy volunteers received diffusion tensor imaging and structural magnetic resonance imaging examinations. Fractional anisotropy maps were compared between groups in the white matter using a voxelwise analysis after intersubject registration to Talairach space. RESULTS: Compared with healthy volunteers, patients demonstrated lower fractional anisotropy values in the left anterior cingulate region in close proximity to the caudate nucleus (95% confidence interval of schizophrenic-healthy: -66 to -20). Using regression analysis, the rate of change in fractional anisotropy differed significantly between groups in this region across the age span examined (10-20 years), after adjusting for group differences in premorbid intellectual capacity and parental socioeconomic status. There were no areas of significantly higher fractional anisotropy in patients compared with healthy volunteers. CONCLUSIONS: These data suggest that early-onset schizophrenia is associated with a disruption in the structural integrity of white matter tracts in the anterior cingulate region. These structural abnormalities may contribute to the deficits in motivation, attention, memory, and higher executive functions in adolescents with 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.     

MRI study of white matter diffusion anisotropy in schizophrenia

Diffusion tensor imaging (DTI) can provide information about brain white matter integrity. The results of DTI studies in schizophrenia are somewhat variable and could benefit from standardized image processing methods. Fourteen patients with schizophrenia or schizoaffective disorder and 14 healthy volunteers underwent DTI. Scans were analyzed using a rigorous voxelwise approach. The key dependent variable, fractional anisotropy, was lower for patients in the corpus callosum, left superior temporal gyrus, parahippocampal gyri, middle temporal gyri, inferior parietal gyri, medial occipital lobe, and the deep frontal perigenual region. Regions showing reduced white matter fractional anisotropy are known to be abnormal in schizophrenia. The voxelwise method used in the current study can provide the basis for hypothesis-driven research.     

Diffusion tensor imaging in schizophrenia: relationship to symptoms

In this diffusion tensor imaging (DTI) study, the authors investigated white matter integrity in schizophrenia and the relationships between white matter alterations and specific symptoms of the disorder. We compared DTI images of 25 schizophrenia patients and 25 matched healthy controls and performed voxel-wise correlational analyses using the patient's DTI data and their severity scores of positive and negative symptoms. We found diffuse deficits in multiple types of white matter tracts in schizophrenia, and an inverse relationship of DTI fractional anisotropy (FA) values with positive symptom scores in association fibers, supporting a "disconnection" hypothesis of positive symptoms in schizophrenia.     

Is depression a disconnection syndrome? Meta-analysis of diffusion tensor imaging studies in patients with MDD

Background: Many studies using diffusion tensor imaging (DTI) have demonstrated impaired white matter integrity in patients with major depressive disorder (MDD), with significant results found in diverse brain regions. We sought to identify whether there are consistent changes of regional white matter integrity in patients with MDD, as shown by decreased fractional anisotropy in DTI. Method: A systematic search strategy was used to identify relevant whole brain voxel-based DTI studies of patients with MDD in relation to comparison groups. Relevant databases were searched for studies published between January 1994 and February 2011 using combinations of the terms "DTI" or "diffusion tensor;" "whole brain" or "voxel-based;" and "depress*." Using the studies that met our inclusion criteria, we performed a meta-analysis of the coordinates of decreased fractional anisotropy using the activation likelihood estimation (ALE) method, which detects 3-dimensional conjunctions of coordinates from multiple studies, weighted by sample size. We then used DTIquery software for fibre tracking to locate the fascicles involved in each region. Results: We included 11 studies with a combined sample of 231 patients with MDD and 261 comparison participants, providing 50 coordinates of decreased fractional anisotropy. Our meta-analysis identified 4 consistent locations of decreased fractional anisotropy in patients with MDD: white matter in the right frontal lobe, right fusiform gyrus, left frontal lobe and right occipital lobe. Fibre tracking showed that the main fascicles involved were the right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, right posterior thalamic radiation and interhemispheric fibres running through the genu and body of the corpus callosum. Limitations: The number of studies included was relatively small, and the DTI data acquisition and analysis techniques were heterogeneous. The ALE method cannot handle studies with no significant group differences. Conclusion: Voxel-based analysis of DTI studies of patients with MDD consistently identified decreased fractional anisotropy in the white matter fascicles connecting the prefrontal cortex within cortical (frontal, temporal and occipital lobes) and subcortical areas (amygdala and hippocampus). This isstrong evidence for the involvement of these neural circuits in the pathology of MDD.     

Correlation between white matter damage and gray matter lesions in multiple sclerosis patients

We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe(superior frontal, middle frontal, precentral, and orbital gyri), right parietal lobe(postcentral and inferior parietal gyri), right temporal lobe(caudate nucleus), right occipital lobe(middle occipital gyrus), right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.     

White matter abnormalities in obsessive-compulsive disorder: a diffusion tensor imaging study

CONTEXT: Several neurobiological models of obsessive-compulsive disorder (OCD) posit a primary role for dysfunction of the anterior cingulate gyrus. Both functional and structural neuroimaging studies have implicated anterior cingulate gray matter abnormalities in the pathophysiology of OCD, but there has been little investigation of the anterior cingulate white matter in this disorder. OBJECTIVE: To test the hypothesis that patients with OCD have abnormal white matter microstructure in the anterior cingulate gyrus compared with healthy volunteers as inferred from diffusion tensor imaging. Additional analyses examined group differences in white matter integrity across the entire brain. DESIGN, SETTING, AND PARTICIPANTS: Fifteen patients with a DSM-IV diagnosis of OCD and 15 healthy volunteers matched for age, sex, and handedness underwent diffusion tensor imaging and structural magnetic resonance imaging examinations. Fractional anisotropy (FA), a robust intravoxel measure of water self-diffusion, was compared between groups on a voxel-by-voxel basis in the anterior cingulate white matter after standardization in Talairach space. MAIN OUTCOME MEASURES: Clinical ratings of symptom severity (ie, Yale-Brown Obsessive-Compulsive Scale) and FA. RESULTS: Compared with healthy volunteers, patients demonstrated significantly lower FA bilaterally in 3 areas of the anterior cingulate gyrus white matter. Additional analyses conducted across the rest of the brain white matter revealed lower FA bilaterally in the parietal region (supramarginal gyri), right posterior cingulate gyrus, and left occipital lobe (lingual gyrus). No areas of significantly higher FA were observed in patients compared with healthy volunteers. Lower FA in the parietal region correlated significantly with higher Yale-Brown Obsessive-Compulsive Scale scores. CONCLUSIONS: These preliminary findings provide evidence of an abnormality that involves the anterior cingulate white matter in the pathogenesis of OCD and are consistent with neurobiological models that posit a defect in connectivity in the anterior cingulate basal ganglia-thalamocortical circuit. White matter abnormalities in other brain regions may also be implicated in the neurobiology of OCD.     

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。