Structural changes in the gray matter of unmedicated patients with obsessive-compulsive disorder: a voxel-based morphometric study

The aim of the current study was to use whole brain voxel-based morphometry（VBM）to assess the gray matter（GM）changes in unmedicated patients with obsessive-compulsive disorder（OCD）compared with normal controls.We compared the GM volumes in28 patients with 22 matched healthy controls using a1.5T MRI.Three-dimensional T1-weighted magnetic resonance images were obtained from all participants.VBM was performed to detect GM volume differences between the two groups.We detected increased regional GM volumes in the bilateral middle temporal gyri,bilateral middle occipital gyri,bilateral globus pallidus,right inferior parietal gyrus,left superior parietal gyrus,right parahippocampus,right supramarginal gyrus,right medial superior frontal gyrus,and left inferior frontal opercular cortex in the OCD patients relative to controls（P〈0.001,uncorrected,cluster size〉100 voxels）.No decreased GM volume was found in the OCD group compared with normal controls.Our findings suggest that structural changes in the GM are not limited to fronto-striato-thalamic circuits in the pathogenesis of OCD.Temporo-parietal cortex may also play an important role.     

Frontal and cingulate gray matter volume reduction in heroin dependence: Optimized voxel-based morphometry

Aims:  Repeated exposure to heroin, a typical opiate, causes neuronal adaptation and may result in anatomical changes in specific brain regions, particularly the frontal and limbic cortices. The volume changes of gray matter (GM) of these brain regions, however, have not been identified in heroin addiction.
Methods:  Using structural magnetic resonance imaging and an optimized voxel-based morphometry approach, the GM volume difference between 15 Chinese heroin-dependent and 15 healthy subjects was tested.
Results:  Compared to healthy subjects, the heroin-dependent subjects had reduced GM volume in the right prefrontal cortex, left supplementary motor cortex and bilateral cingulate cortices.
Conclusion:  Frontal and cingulate atrophy may be involved in the neuropathology of heroin dependence.     

Reduced left hemispheric white matter volume in twins with bipolar I disorder.

BACKGROUND: Although the heritability of bipolar I disorder (BPI) is high, few magnetic resonance imaging (MRI) studies of siblings of bipolar patients exist. We performed MRI brain scans on a nationwide sample of twins with BPI, as well as on their co-twins and a demographically balanced sample of control twin subjects, to detect any structural alterations related to the disorder and to the increased genetic risk. METHODS: The National Hospital Discharge Register, National Population Register, and Finnish Twin Cohorts were used to identify bipolar twins. Structured diagnostic interviews and MRI scans were obtained for 24 twins with BPI, 15 healthy co-twins, and 27 control twin subjects. RESULTS: Patients and co-twins showed a significant decrease in left hemispheric white matter volume. The disparity in patients was -16.1 cm(3) (95% confidence interval [CI] -26.6, -5.6) and in co-twins -11.3 cm(3) (95% CI -22.1, -0.4) compared with control twin subjects. No gray matter decrease was seen in patients or co-twins. CONCLUSIONS: The results of this first large-scale MRI study of twins with BPI, their co-twins, and appropriate control twin subjects, suggest that alterations of the left hemisphere white matter in BPI may reflect genetic factors predisposing to the disorder.     

Greater cortical gray matter density in lithium-treated patients with bipolar disorder.

BACKGROUND: The neurobiological underpinnings of bipolar disorder are not well understood. Previous neuroimaging findings have been inconsistent; however, new methods for three-dimensional (3-D) computational image analysis may better characterize neuroanatomic changes than standard volumetric measures. METHODS: We used high-resolution magnetic resonance imaging and cortical pattern matching methods to map gray matter differences in 28 adults with bipolar disorder, 70% of whom were lithium-treated (mean age = 36.1 +/- 10.5; 13 female subject), and 28 healthy control subjects (mean age = 35.9 +/- 8.5; 11 female subjects). Detailed spatial analyses of gray matter density (GMD) were conducted by measuring local proportions of gray matter at thousands of homologous cortical locations. RESULTS: Gray matter density was significantly greater in bipolar patients relative to control subjects in diffuse cortical regions. Greatest differences were found in bilateral cingulate and paralimbic cortices, brain regions critical for attentional, motivational, and emotional modulation. Secondary region of interest (ROI) analyses indicated significantly greater GMD in the right anterior cingulate among lithium-treated bipolar patients (n = 20) relative to those not taking lithium (n = 8). CONCLUSIONS: These brain maps are consistent with previous voxel-based morphometry reports of greater GMD in portions of the anterior limbic network in bipolar patients and suggest neurotrophic effects of lithium as a possible etiology of these neuroanatomic differences.     

Cortical gray matter deficit in patients with bipolar disorder

Background: cortical gray matter volume deficit and ventricular enlargement are well documented in schizophrenia, but their presence in bipolar disorder is less well established.

Methods: global cortical gray matter, white matter and sulcal CSF, as well as lateral and third ventricular volume measures, were derived from axial MRI brain images obtained on age-matched bipolar (n=9), schizophrenic (n=9), and control (n=16) subjects. All subjects were free of history of alcohol or other substance dependence.

Results: relative to controls, bipolar patients had widespread volume deficits of cortical gray matter but not of cortical white matter. Schizophrenic patients had an even more severe cortical gray matter deficit and greater sulcal and lateral ventricular enlargement than the bipolar patients.

Conclusions: this group of patients with bipolar disorder had a widespread deficit of cortical gray matter similar to, but less pronounced than, that observed in patients with schizophrenia.     

Voxel-based morphometric analysis on the volume of gray matter in bipolar I disorder

A number of previous studies have found that bipolar disorder is associated with abnormalities of brain structure. In this study we used optimized voxel-based morphometry (VBM) to compare gray matter volume between patients with bipolar I disorder and healthy controls. Twenty-four bipolar I patients (15 males and nine females) and 36 healthy controls (21 males and 15 females), who were well matched for age and gender, were scanned using structural magnetic resonance imaging. Gray matter volume was assessed and compared using optimized VBM, and the correlation between duration of illness/number of episodes and regional volumes was analyzed. There was no difference in whole-brain gray matter volume between the two groups. Optimized vVBM showed that subjects with bipolar I disorder had smaller volumes in the left inferior parietal lobule, right superior temporal gyrus, right middle frontal gyrus and left caudate. Only the volume of the right middle frontal gyrus was correlated with duration of illness and number of episodes in patients. These results suggest widespread gray matter defects in bipolar I disorder, which may play an important role in onset of the illness.     

Progressive gray matter loss in patients with bipolar disorder.

BACKGROUND: Structural brain abnormalities of the medial temporal lobe have been found in people with bipolar disorder (BPD). It is not known whether these abnormalities progress over the course of the illness or how they relate to neuropsychologic functioning. We sought to address these uncertainties in a prospective cohort study of people with bipolar I disorder. METHODS: Twenty patients with bipolar I disorder and 21 control subjects were recruited from the community. Participants were group matched for age, sex, and premorbid IQ. Longitudinal change in gray matter density was assessed using magnetic resonance imaging and evaluated using the technique of tensor-based morphometry with SPM2 software. Changes in gray and white matter density were estimated and compared with changes in cognitive function and clinical outcome. RESULTS: Patients with BPD showed a larger decline in hippocampal, fusiform, and cerebellar gray matter density over 4 years than control subjects. No significant changes in white matter density were found. Reductions in temporal lobe gray matter correlated with decline in intellectual function and with the number of intervening mood episodes over the follow-up period. CONCLUSIONS: Patients with BPD lose hippocampal, fusiform and cerebellar gray matter at an accelerated rate compared with healthy control subjects. This tissue loss is associated with deterioration in cognitive function and illness course.     

Reduced anterior and posterior cingulate gray matter in borderline personality disorder.

BACKGROUND: Structural abnormalities in prefrontal and cingulate gyrus regions-important in affective processing, impulse control and cognition may contribute to the psychopathology of borderline personality disorder (BPD). Previous MRI studies examining volume have reported that compared with healthy controls, BPD patients have decreases in right anterior cingulate, no differences in dorsolateral prefrontal cortex, and mixed findings for prefrontal cortex. We extended this investigation by examining gray and white matter volume of frontal and cingulate gyrus Brodmann areas (BAs) in a large group of patients and healthy controls. METHODS: MRI scans were acquired in 50 BPD patients (n = 13 with comorbid diagnosis of BPD and Schizotypal Personality Disorder (SPD) and n = 37 without SPD) and 50 healthy controls, and gray/white matter volume in cingulate gyrus and frontal lobe BAs were assessed. Normal BPD and BPD subgroup comparisons were conducted. RESULTS: Compared with controls, BPD patients showed reduced gray matter volume in BA 24 and 31 of the cingulate. BPD patients without comorbid SPD had isolated gray matter volume loss in BA 24, but were spared for BA 31 in contrast to BPD patients with SPD. There were no group differences in whole cingulate or frontal lobe volume. CONCLUSIONS: The finding of more pervasive cingulate shrinkage in the patients with BPD and SPD comorbidity resembles recent observations with the same methods in patients with schizophrenia. The pattern of reduced anterior and posterior cingulate gray matter volume in BPD patients, particularly those comorbid for SPD is consistent with the affective and attentional deficits observed in these personality disorders.     

反社会人格障碍男性青年大脑白质异常改变： 证据来自于基于体素脑形态测量学的DARTEL分析

SPM8 DARTEL工具包对3D脑结构成像数据对男性青年反社会人格障碍者和正常组的大脑白质结构进行基于体素的形态学分析（VBM）。结果显示,与正常对照者比较,反社会人格障碍者主要表现为双侧前额叶、右岛叶、中央前回,左右颞上回、右中央后回、右侧顶下小叶、右侧楔前叶、右枕中叶、右海马旁回及双侧扣带回等多个脑区白质体积密度增加,左颞中叶、右小脑的白质体积密度减小。相关分析显示,额内侧回的白质体积密度增加与反社会行为的评分(PDQ)有正相关。提示反社会人格障碍者存在多个脑区的白质形态学明显异常,这些异常可能与其反社会行为有关。     

White matter lesions in euthymic patients with bipolar disorder

Objective: We aimed to quantify both load and regional distributions of hyperintensities on magnetic resonance imaging (MRI) in prospectively verified euthymic bipolar patients and matched controls. Method: Cerebral hyperintensities on T2, proton density and fluid‐attenuated inversion recovery (FLAIR) MRI were compared between 48 bipolar and 47 control subjects using semi‐quantitative rating scales. Results: Bipolar subjects had more severe frontal deep white matter lesions (DWML). Hyperintensity load was independent of age in bipolar patients but increased with age in controls. Global prevalence and severity of hyperintensities did not differ between groups. Exploratory analysis showed DWML in excess in the left hemisphere in bipolar subjects but not in controls. Conclusion: Findings are consistent with clinical, particularly some neurocognitive, features of bipolar disorder and implicate fronto‐subcortical circuits in its neurobiology. They more probably reflect a trait abnormality or illness scar rather than a mood state‐dependent finding. Processes other than ageing and vascular factors may underlie their development.     

Voxel-based study of structural changes in first-episode patients with bipolar disorder.

BACKGROUND: Although morphometric studies of bipolar disorder (BD) suggest that neurofunctional abnormalities reflect underlying structural changes, it remains unclear whether abnormalities are present at illness onset or reflect disease progression. Previous voxel-based morphometry (VBM) findings suggest that ventrolateral prefrontal cortex (VLPFC) changes develop over time, whereas morphologic abnormalities elsewhere in the anterior limbic network (ALN) are present early in BD. In this study, we used VBM to explore structural brain changes in first-episode bipolar patients. METHODS: First-episode bipolar (n = 33) and healthy (n = 33) subjects underwent magnetic resonance imaging. Images were normalized and compared on a voxel-by-voxel basis. RESULTS: Bipolar subjects showed no change in VLPFC density or volume. We observed increased volume in left thalamus and fusiform and cerebellum bilaterally; increased gray matter density in anterior cingulate and posterior parietal structures; and increased gray matter volume and density in middle/superior temporal and posterior cingulate gyri. No areas of decreased volume or density were observed. CONCLUSIONS: These data indicate that structural changes are absent from VLPFC early in the course of BD. Morphologic abnormalities are present in other portions of the ALN and in structures previously observed to mediate neurofunctional changes in BD, suggesting that dysfunctional neuronal proliferation or pruning may occur in bipolar patients.     

Changes in gray matter volume in patients with bipolar disorder.

BACKGROUND: Several lines of evidence suggest the presence of neurofunctional abnormalities in patients with bipolar disorder. These functional abnormalities may stem from structural pathology in these or connected brain regions. Previous studies have generally used a region of interest (ROI) approach to study morphologic changes in bipolar disorder with inconsistent findings among research groups, which may reflect differences in how ROIs are defined. Voxel based morphometry (VBM) allows a more exploratory analysis without the necessity for predefined anatomic boundaries. In this study we utilized VBM to compare gray matter volume between groups of bipolar and healthy subjects. METHODS: Thirty-two patients with bipolar disorder and 27 healthy subjects participated in structural magnetic resonance imaging (MRI) scans. MRI images were segmented, normalized to a standard stereotactic space, and compared on a voxel-by-voxel basis using statistical parametric mapping. RESULTS: Bipolar subjects showed increased gray matter in several regions including portions of anterior cingulate, ventral prefrontal cortex, fusiform gyrus and parts of the primary and supplementary motor cortex. Bipolar subjects showed decreased gray matter volume in superior parietal lobule. CONCLUSIONS: These data support suggestions that neurofunctional deficits are related to structural brain abnormalities in patients with bipolar disorder. The increased gray matter observed in several regions suggests that some affected areas may demonstrate volumetric expansion, at least in some patient populations.     

Diagnosis-related regional gray matter loss over two years in first episode schizophrenia and bipolar disorder.

BACKGROUND: We examined gray- and white-matter brain volumes in first episode psychosis (FEP) at initial presentation and at two-year follow-up. We predicted that FEP subjects would show longitudinal reductions in fronto-temporal gray- and white-matter volumes compared with controls. Furthermore, we expected groups to be differentiated by diagnosis-related reductions. METHODS: Twenty-five schizophrenia and 8 bipolar disorder FEP patients underwent a structural MRI scan at first presentation and 2 years later. Matched healthy subjects (n = 22) underwent a single identical scan. RESULTS: At initial presentation FEP subjects had significantly less gray- and white-matter than healthy subjects. Diagnostic dissociations were revealed both at first presentation and at follow-up. In schizophrenia patients, gray-matter deficits were observed in lateral and medial frontal regions and in bilateral posterior temporal lobe regions, with additional extensive losses over time in lateral fronto-temporal regions and left anterior cingulate gyrus. By contrast, gray matter deficit in bipolar patients was localized to bilateral inferior temporal gyri with additional loss over time observed only in the anterior cingulate cortex. CONCLUSIONS: The results are consistent with a dual process model of psychosis, in which the diagnosis-related gray matter loss is determined by neurodevelopmental gray-matter volumetric differences which predate symptom onset, and diagnosis-related neurodegenerative gray-matter loss over time.     

Regional prefrontal gray and white matter abnormalities in bipolar disorder.

BACKGROUND: Previous magnetic resonance imaging (MRI) studies indicate that compared with healthy volunteers, patients with bipolar disorder have structural and functional abnormalities in the prefrontal cortex. The aim of this study was to investigate differences in prefrontal subregions between bipolar patients and healthy subjects. METHODS: Bipolar patients hospitalized for a manic episode (n = 17), and demographically matched healthy volunteers (n = 12) were recruited. Contiguous 1-mm coronal T1-weighted MRI slices were obtained using a Picker 1.5 Tesla scanner. The gray and white matter volumes of five prefrontal subregions of interest were measured: superior, middle, inferior, cingulate, and orbital. RESULTS: Bipolar patients had smaller left prefrontal gray matter volumes, specifically in the middle and superior subregions and smaller right prefrontal gray matter volumes, specifically in the inferior and middle subregions. White matter differences were not observed in any of the prefrontal subregions. CONCLUSIONS: The results suggest that bipolar patients have subregion-specific gray matter volume reductions in the prefrontal cortex as compared to healthy subjects. Further investigations into the role of specific prefrontal subregions in bipolar disorder are warranted.     

State-dependent microstructural white matter changes in bipolar I depression

Abnormalities in fronto-limbic-striatal white matter (WM) have been reported in bipolar disorder (BD), but results have been inconsistent across studies. Furthermore, there have been no detailed investigations as to whether acute mood states contribute to microstructural changes in WM tracts. In order to compare fiber density and structural integrity within WM tracts between BD depression and remission, whole-brain fractional anisotropy (FA) and mean diffusivity (MD) were assessed in 37 bipolar I disorder (BD-I) patients (16 depressed and 21 remitted), and 26 healthy individuals with diffusion tensor imaging. Significantly decreased FA and increased MD in bilateral prefronto-limbic-striatal white matter and right inferior fronto-occipital, superior and inferior longitudinal fasciculi were shown in all BD-I patients versus controls, as well as in depressed BD-I patients compared to both controls and remitted BD-I patients. Depressed BD-I patients also exhibited increased FA in the ventromedial prefrontal cortex. Remitted BD-I patients did not differ from controls in FA or MD. These findings suggest that BD-I depression may be associated with acute microstructural WM changes.     

Anterior cingulate volumes associated with trait impulsivity in individuals with bipolar disorder

Objective:  Impulsivity is associated with the clinical outcome and likelihood of risky behaviors among bipolar disorder (BD) patients. Our previous study showed an inverse relationship between impulsivity and orbitofrontal cortex (OFC) volume in healthy subjects. We hypothesized that BD patients would show an inverse relationship between impulsivity and volumes of the OFC, anterior cingulate cortex (ACC), medial prefrontal cortex, and amygdala, which have been implicated in the pathophysiology of BD.
Methods:  Sixty-three BD patients were studied (mean ± SD age = 38.2 ± 11.5 years; 79% female). The Barratt Impulsiveness Scale (BIS), version 11A, was used to assess trait impulsivity. Images were processed using SPM2 and an optimized voxel-based morphometry protocol. We examined the correlations between BIS scores and the gray matter (GM) and white matter (WM) volumes of the prespecified regions.
Results:  Left rostral ACC GM volume was inversely correlated with the BIS total score ( t  =   3.95, p_corrected = 0.003) and the BIS motor score ( t  =   5.22, p_corrected < 0.001). In contrast to our hypothesis, OFC volumes were not significantly associated with impulsivity in BD. No WM volume of any structure was significantly correlated with impulsivity. No statistical association between any clinical variable and the rostral ACC GM volumes reached significance.
Conclusions:  Based on our previous findings and the current results, impulsivity may have a different neural representation in BD and healthy subjects, and the ACC may be involved in the pathophysiology of abnormal impulsivity regulation in BD patients.     

Preliminary evidence of within-subject changes in gray matter density associated with remission of bipolar depression

A preliminary within-subjects MRI study of seven patients with a diagnosis of bipolar I disorder revealed that, compared to remission, depression was associated with gray matter density increases in subgenual prefrontal cortex, parahippocampal gyrus, and inferior temporal gyri. Decreases were observed in superior and inferior frontal gyri and anterior cingulate.     

Grey matter differences in bipolar disorder: a meta-analysis of voxel-based morphometry studies

Selvaraj S, Arnone D, Job D, Stanfield A, Farrow TFD, Nugent AC, Scherk H, Gruber O, Chen X, Sachdev PS, Dickstein DP, Malhi GS, Ha TH, Ha K, Phillips ML, McIntosh AM. Grey matter differences in bipolar disorder: a meta‐analysis of voxel‐based morphometry studies. Bipolar Disord 2012: 14: 135–145. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Several neuroimaging studies have reported structural brain differences in bipolar disorder using automated methods. While these studies have several advantages over those using region of interest techniques, no study has yet estimated a summary effect size or tested for between‐study heterogeneity. We sought to address this issue using meta‐analytic techniques applied for the first time in bipolar disorder at the level of the individual voxel. Methods: A systematic review identified 16 voxel‐based morphometry (VBM) studies comparing individuals with bipolar disorder with unaffected controls, of which eight were included in the meta‐analysis. In order to take account of heterogeneity, summary effect sizes were computed using a random‐effects model with appropriate correction for multiple testing. Results: Compared with controls, subjects with bipolar disorder had reduced grey matter in a single cluster encompassing the right ventral prefrontal cortex, insula, temporal cortex, and claustrum. Study heterogeneity was widespread throughout the brain; though the significant cluster of grey matter reduction remained once these extraneous voxels had been removed. We found no evidence of publication bias (Eggers p = 0.63). Conclusions: Bipolar disorder is consistently associated with reductions in right prefrontal and temporal lobe grey matter. Reductions elsewhere may be obscured by clinical and methodological heterogeneity.     

Frontal lobe activation during word generation studied by functional MRI

Aims – To further delimit the specific verbal operations occurring in the dorsolateral frontal cortex during the generation of words, methods – different verbal fluency tasks guided by distinct specifications (phonological, semantic, or automatic production of words) were used in a functional magnetic resonance study. The study group comprised 10 right-handed normal subjects ranging in age from 23 to 27 years. Functional magnetic resonance images were obtained in a 1.5-Tesla magnet using a spoiled GRASS sequence. Results – Noticeable activation was found during the word generation tasks in the dorsolateral frontal cortex. The region showing the most prominent activation was the posterior part of the left middle frontal gyrus. Nevertheless, the different tasks each had a different activation effect. The phonologically guided generation of words produced the most consistent activation of the middle frontal gyrus, which mainly involved the premotor cortex. Conclusion – The results suggest that operations concerned with the generation of sound sequences, rather than the amount of produced words or their semantics, are responsible for sustained focal activity observed in the frontal lobes during verbal fluency tasks.