Parahippocampal gray matter density in panic disorder: a voxel-based morphometric study

OBJECTIVE: The authors examined possible cerebral gray matter abnormalities in patients with panic disorder. METHOD: Gray matter concentration in 18 panic disorder outpatients and 18 healthy subjects was compared by using a voxel-based morphometry approach. RESULTS: Gray matter density of the left parahippocampal gyrus was significantly lower in patients with panic disorder compared with healthy subjects. CONCLUSIONS: This result provides further support for the involvement of the parahippocampal area in the pathophysiology of panic disorder.     

Regional gray matter abnormalities in panic disorder: a voxel-based morphometry study

Although abnormalities in brain structures involved in the neurobiology of fear and anxiety have been implicated in the pathophysiology of panic disorder (PD), relatively few studies have made use of voxel-based morphometry (VBM) magnetic resonance imaging (MRI) to determine structural brain abnormalities in PD. We have assessed gray matter volume in 19 PD patients and 20 healthy volunteers using VBM. Images were acquired using a 1.5 T MRI scanner, and were spatially normalized and segmented using optimized VBM. Statistical comparisons were performed using the general linear model. A relative increase in gray matter volume was found in the left insula of PD patients compared with controls. Additional structures showing differential increases were the left superior temporal gyrus, the midbrain, and the pons. A relative gray matter deficit was found in the right anterior cingulate cortex. The insula and anterior cingulate abnormalities may be relevant to the pathophysiology of PD, since these structures participate in the evaluation process that ascribes negative emotional meaning to potentially distressing cognitive and interoceptive sensory information. The abnormal brain stem structures may be involved in the generation of panic attacks.     

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.     

Regional gray matter changes in shift workers: a voxel-based morphometry study

ObjectivePrevious neuroimaging studies have shown subtle structural changes of the brain in various sleep disorders, suggesting detrimental effects of disrupted sleep–wake cycle on brain structures. We aimed to identify structural changes in shift workers relative to day workers. We hypothesized that brain structures belonging to sleep–wake modulation may be altered in shift workers.MethodsNineteen male shift workers (median age, 21 years) and 19 male day workers (median age, 21 years) voluntarily participated in the current study. Sleep questionnaires were obtained from all participants and compared between the groups. Voxel-based morphometry was used to compare regional gray matter volume between shift workers and day workers (corrected p < 0.05 with small volume correction). Separate correlation analyses were performed between regional gray matter volume change and scores of Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index (Pearson's correlation, p < 0.05).ResultsCompared to day workers, shift workers had higher scores of Beck Depression Inventory-II, Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index. Compared to day workers, shift workers had a significant gray matter volume reduction in the pontomesencephalic tegmentum. Regional volume of the pontomesencephalic tegmentum negatively correlated with Pittsburgh Sleep Quality Index global score.ConclusionsWe observed that pontomesencephalic tegmentum volume was reduced in shift workers compared to day workers and that the smaller pontomesencephalic tegmentum volume was related to the poorer sleep quality. Our preliminary findings may be related to chronic disruption of circadian rhythm or decreased exposure to bright light in shift workers.     

Regional gray matter abnormalities in obsessive-compulsive disorder: a voxel-based morphometry study.

BACKGROUND: Several structural magnetic resonance imaging (MRI) studies have investigated the presence of brain abnormalities in obsessive-compulsive disorder (OCD) but have not produced consistent findings. This might be partly related to their use of a regions-of-interest approach. We assessed gray matter volumes in 19 OCD subjects and 15 healthy volunteers, using voxel-based morphometry (VBM). METHODS: Images were acquired with a 1.5-T MRI scanner, spatially normalized, and segmented with optimized VBM. Statistical comparisons were performed with the general linear model. RESULTS: Significant findings were detected in regions predicted a priori to be implicated in OCD, including increased gray matter in OCD subjects relative to control subjects in posterior orbitofrontal and parahippocampal regions; decreased gray matter in OCD patients in the left anterior cingulate cortex; and inverse correlations between obsessive-compulsive symptom severity and gray matter in the medial thalamus (p < .001, uncorrected for multiple comparisons). Also, an unpredicted site of gray matter reduction in OCD patients in the right parietal associative cortex approached significance (p = .052, corrected for multiple comparisons). CONCLUSIONS: Our findings are consistent with previous studies implicating dysfunction of orbitofrontal, cingulate, thalamic, and temporolimbic regions in OCD and suggest that the involvement of the parietal cortex in the pathophysiology of OCD warrants further investigation.     

Regional gray matter abnormalities in panic disorder: A voxel-based morphometry study

Although abnormalities in brain structures involved in the neurobiology of fear and anxiety have been implicated in the pathophysiology of panic disorder (PD), relatively few studies have made use of voxel-based morphometry (VBM) magnetic resonance imaging (MRI) to determine structural brain abnormalities in PD. We have assessed gray matter volume in 19 PD patients and 20 healthy volunteers using VBM. Images were acquired using a 1.5 T MRI scanner, and were spatially normalized and segmented using optimized VBM. Statistical comparisons were performed using the general linear model. A relative increase in gray matter volume was found in the left insula of PD patients compared with controls. Additional structures showing differential increases were the left superior temporal gyrus, the midbrain, and the pons. A relative gray matter deficit was found in the right anterior cingulate cortex. The insula and anterior cingulate abnormalities may be relevant to the pathophysiology of PD, since these structures participate in the evaluation process that ascribes negative emotional meaning to potentially distressing cognitive and interoceptive sensory information. The abnormal brain stem structures may be involved in the generation of panic attacks.     

Reduced gray matter volume of dorsal cingulate cortex in patients with obsessive-compulsive disorder: a voxel-based morphometric study

Aims: Previous morphometric studies using magnetic resonance imaging (MRI) have revealed structural brain abnormalities in obsessive–compulsive disorder (OCD). The aim of the present study was to investigate the alterations in brain structure of patients with OCD using a voxel‐based morphometry (VBM) method. Methods: Sixteen patients with OCD free of comorbid major depression, and 32 sex‐ and age‐matched healthy subjects underwent MRI using a 1.5‐T MR scanner. OCD severity was assessed with the Yale–Brown Obsessive–Compulsive Scale (mean ± SD: 22 ± 7.6; range: 7–32). MR images were spatially normalized and segmented using the VBM5 package ( http://dbm.neuro.uni‐jena.de/vbm/ ). Statistical analysis was performed using statistical parametric mapping software. Results: Significant reductions in regional gray matter volume were detected in the left caudal anterior cingulate cortex and right dorsal posterior cingulate cortex in the patients with OCD as compared to healthy controls (uncorrected, P < 0.001). No significant differences in white matter volumes were observed in any brain regions of the patients. No significant correlation between Yale–Brown Obsessive–Compulsive Scale score and regional gray matter or white matter volume was observed. Conclusions: Regional gray matter alteration in the dorsal cingulate cortex, which is suggested to play a role in non‐emotional cognitive processes, may be related to the pathophysiology in OCD.     

White matter abnormalities in bipolar disorder: a voxel-based diffusion tensor imaging study

Objectives:  In bipolar disorder (BD), dysregulation of mood may result from white matter abnormalities that disrupt fronto-subcortical circuits. In this study, we explore such abnormalities using diffusion tensor imaging (DTI), an imaging technique capable of detecting subtle changes not visible with conventional magnetic resonance imaging (MRI), and voxel-based analysis.
Methods:  Thirty-six patients with BD, all but two receiving antidepressants or mood stabilizers, and 28 healthy controls matched for age and gender were studied. Diffusion-weighted echoplanar images (DW-EPI) were obtained using a 1.5T scanner. Voxel-based analysis was performed using SPM 2. Differences between the groups in mean diffusivity and fractional anisotropy (FA) were explored.
Results:  In the patient group, mean diffusivity was increased in the right posterior frontal and bilateral prefrontal white matter, while FA was increased in the inferior, middle temporal and middle occipital regions. The areas of increased mean diffusivity overlapped with those previously found to be abnormal using volumetric MRI and magnetization transfer imaging (MTI) in the same group of patients.
Conclusions:  White matter abnormalities, predominantly in the fronto-temporal regions, can be detected in patients with BD using DTI. The neuropathology of these abnormalities is uncertain, but neuronal and axonal loss, myelin abnormalities and alterations in axonal packing density are likely to be relevant. The neuroprotective effects of some antidepressants and mood stabilizers make it unlikely that medication effects could explain the abnormalities described here, although minor effects cannot be excluded.     

Regional brain gray matter volume differences in patients with bipolar disorder as assessed by optimized voxel-based morphometry.

BACKGROUND: Structural magnetic resonance imaging (MRI) studies of regions of interest in brain have been inconsistent in demonstrating volumetric differences in subjects with bipolar disorder (BD). Voxel-based morphometry (VBM) provides an unbiased survey of the brain, can identify novel brain areas, and validates previously hypothesized regions. We conducted both optimized VBM, comparing MRI gray matter volume, and traditional VBM, comparing MRI gray matter density, in 11 BD subjects and 31 healthy volunteers. To our knowledge, these are the first VBM analyses of BD. METHODS: Segmented MRI gray matter images were normalized into standardized stereotactic space, modulated to allow volumetric analysis (optimized only), smoothed, and compared at the voxel level with statistical parametric mapping. RESULTS: Optimized VBM showed that BD subjects had smaller volume in left ventromedial temporal cortex and bilateral cingulate cortex and larger volume in left insular/frontoparietal operculum cortex and left ventral occipitotemporal cortex. Traditional VBM showed that BD subjects had less gray matter density in left ventromedial temporal cortex and greater gray matter density in left insular/frontoparietal operculum cortex and bilateral thalamic cortex. Exploratory analyses suggest that these abnormalities might differ according to gender. CONCLUSIONS: Bipolar disorder is associated with volumetric and gray matter density changes that involve brain regions hypothesized to influence mood.     

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.     

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.     

Regional gray matter atrophy in early primary progressive multiple sclerosis: a voxel-based morphometry study

BACKGROUND: Gray matter (GM) atrophy has been reported in multiple sclerosis (MS). However, little is known about its regional distribution. OBJECTIVE: To investigate the regional distribution of GM atrophy in clinically early primary progressive MS (PPMS). DESIGN AND PATIENTS: Thirty-one patients with PPMS within 5 years of symptom onset (mean age, 43.2 years; median Expanded Disability Status Scale score, 4.5) and 15 healthy control subjects (mean age, 43.7 years) were studied. All subjects underwent a 3-dimensional inversion-recovery fast spoiled gradient-recalled echo sequence that was repeated after 1 year in patients only. Magnetic resonance images underwent an optimized voxel-based morphometric analysis that segments magnetic resonance data volumes in a normalized space and quantifies tissue atrophy on a voxel-by-voxel basis. A lesion mask was created for each patient and used in normalization and segmentation steps to minimize bias from lesions. A multisubject design was used in the cross-sectional study to compare patients with PPMS and controls. A 1-way analysis of variance (within-subjects) design was used in the longitudinal study. RESULTS: At baseline, patients with PPMS displayed bilateral thalamic atrophy compared with controls. In addition, a significant association between lesion load and decreased GM volume was found for the thalami. Loss of GM in the putamen, caudate, thalami, and cortical and infratentorial areas was observed in patients after 1 year of follow-up. CONCLUSIONS: Atrophy is most obvious in deep GM in clinically early PPMS. This may reflect increased sensitivity of these regions to neurodegeneration. Cortical and infratentorial atrophy developed as the disease evolved.     

Putaminal gray matter volume decrease in panic disorder: an optimized voxel-based morphometry study

Our study aimed to identify gray matter volume differences between panic disorder patients and healthy volunteers using optimized voxel-based morphometry. Gray matter volume was compared between 18 panic subjects and 18 healthy volunteers. Panic disorder severity scale (PDSS) and Zung self-rating anxiety scale (Z-SAS) were administered. Gray matter volumes of bilateral putamen were decreased in panic subjects relative to healthy comparison subjects (corrected P < 0.05). Decreased gray matter volume was also observed in the right precuneus, right inferior temporal gyrus, right inferior frontal gyrus, left superior temporal gyrus, and left superior frontal gyrus at a less conservative level of significance. PDSS score negatively correlated with gray matter volume in the left putamen, right putamen, right inferior frontal gyrus, and left superior frontal gyrus in panic subjects. The duration of illness negatively correlated with left putaminal gray matter volume. There was also a negative correlation between gray matter volume in right putamen and Z-SAS score in panic subjects. The current study reports a putaminal gray matter volume decrease in panic subjects, which may be related to the clinical severity of panic disorder.     

Increased gray matter density in patients with schizophrenia and cannabis use: a voxel-based morphometric study using DARTEL

Alterations in gray matter density as well as cognitive impairments are commonly described in patients with schizophrenia (SCH patients). Both gray matter deficits and cognitive impairments have recently been discussed to represent vulnerability markers of schizophrenia. The counterintuitive finding of better cognitive performance in patients with schizophrenia and cannabis use (SCH+CAN patients) compared to cannabis na?ve patients is discussed as a reflection of lower vulnerability for schizophrenia in at least one subgroup of SCH+CAN patients. We hypothesized that SCH+CAN patients would display fewer gray matter deficits compared to SCH patients reflecting their presumed lower vulnerability. We therefore compared gray matter density in 30 first episode SCH+CAN and 24 first episode SCH patients using a fast diffeomorphic registration algorithm (DARTEL) and voxel-based morphometry (VBM). We found less severe cognitive impairments and middle frontal gray matter deficits in the SCH+CAN patients. In the pooled sample gray matter density was positively associated with cognitive functioning. Results may support the hypothesis of a lower biological vulnerability in at least one subgroup of SCH+CAN patients.     

Increased brainstem volume in panic disorder: a voxel-based morphometric study

Neurocircuitry models of panic disorder have hypothesized that the panic attack itself stems from loci in the brainstem including the ascending reticular system and respiratory and cardiovascular control centers. Voxel-based morphometry with acobian modulation was used to examine gray matter volume changes in 10 panic disorder patients and 23 healthy controls. The panic disorder patients had a relatively increased gray matter volume in the midbrain and rostral pons of the brainstem. Increased ventral hippocampal and decreased regional prefrontal cortex volumes were also noted at a lower significance threshold. This finding has implications for pathophysiologic models of panic disorder, and provides structural evidence for the role of the brainstem in neurocircuitry models of panic disorder.     

Regional gray matter changes in obsessive-compulsive disorder: relationship to clinical characteristics

Regional brain volumes were compared between 23 participants with obsessive-compulsive disorder (OCD) and 36 healthy controls using magnetic resonance imaging with voxel-based morphometry. A volumetric decrease in OCD was found in the right mediofrontal cortex. An increase was found in the left temporoparietal cortex. Volume alterations were related to symptom severity and age of onset.     

Different gray matter patterns in chronic schizophrenia and chronic bipolar disorder patients identified using voxel-based morphometry

Gray matter (GM) volume deficits have been described in patients with schizophrenia (Sz) and bipolar disorder (BD), but to date, few studies have directly compared GM volumes between these syndromes with methods allowing for whole-brain comparisons. We have used structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) to compare GM volumes between 38 Sz and 19 BD chronic patients. We also included 24 healthy controls. The results revealed a widespread cortical (dorsolateral and medial prefrontal and precentral) and cerebellar deficit as well as GM deficits in putamen and thalamus in Sz when compared to BD patients. Besides, a subcortical GM deficit was shown by Sz and BD groups when compared to the healthy controls, although a putaminal reduction was only evident in the Sz patients. In this comparison, the BD patients showed a limited cortical and subcortical GM deficit. These results support a partly different pattern of GM deficits associated to chronic Sz and chronic BD, with some degree of overlapping.     

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.     

Light to moderate alcohol use is associated with increased cortical gray matter in middle-aged men: a voxel-based morphometric study

We examined the associations of current alcohol consumption with brain morphometric measures in a healthy, community-dwelling cohort. Cranial T1-weighted 3D-structural MRI scans were obtain in 383 adults (men=211) aged 60-64 years, randomly selected form the larger PATH Through Life study. Voxel-based morphometric analyses were applied to detect regional gray matter and white matter volume changes related to reported weekly alcohol consumption (mean 7.04+/-8.15 drinks per week). Alcohol consumption in men had a linear association with greater gray matter in bilateral superior and medial frontal gyrus, bilateral middle occipital gyrus, right inferior parietal gyrus, bilateral precentral gyrus, left paracentral gyrus, left uncus and left inferior occipital gyrus, and with lesser white matter in bilateral superior temporal and left parahippocampal gyrus, after adjustment for age, education, total intracranial volume, smoking, hypertension, diabetes and hyperlipidemia. In women, there was no significant linear association between alcohol consumption and total or regional brain volumes. Our results showed a dose-related, sexually dimorphic impact of alcohol on brain tissue volumes independent of cerebrovascular risk factors. These findings are consistent with an inverse-U association between alcohol use and brain morphometry, while suggesting an increased vulnerability of white matter to alcohol-related brain damage.     

Increased striatal gray matter densities in patients with schizophrenia and substance use disorder: a voxel-based morphometry study

We sought to investigate the link between substance abuse and increased striatal gray matter densities (GMD) in schizophrenia, using voxel-based morphometry (VBM). Increased striatal GMD were found in patients with schizophrenia and substance use disorder (n=12), but not schizophrenia only patients (n=11), compared to healthy volunteers (n=15).