White Matter Volume Abnormalities Research Articles

Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study

IntroductionRegional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool.Methods15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the standardized ENIGMA-VBM tool. Statistical parametric T-maps were generated from each cohort and meta-analyzed to reveal voxel-wise differences between EOP and healthy controls as well as the individual-based association between GM volume and age of onset, chlorpromazine (CPZ) equivalent dose, and other clinical variables.ResultsCompared with healthy controls, individuals with EOP showed widespread lower GM volume encompassing most of the cortex, with the most marked effect in the left median cingulate (Hedges’ g = 0.55, p = 0.001 corrected), as well as small clusters of lower white matter (WM), whereas no regional GM or WM volumes were higher in EOP. Lower GM volume in the cerebellum, thalamus and left inferior parietal gyrus was associated with older age of onset. Deficits in GM in the left inferior frontal gyrus, right insula, right precentral gyrus and right superior frontal gyrus were also associated with higher CPZ equivalent doses.ConclusionEOP is associated with widespread reductions in cortical GM volume, while WM is affected to a smaller extent. GM volume alterations are associated with age of onset and CPZ equivalent dose but these effects are small compared to case-control differences. Mapping anatomical abnormalities in EOP may lead to a better understanding of the role of psychosis in brain development during childhood and adolescence.

Obesity is associated with greater cognitive function in patients with type 2 diabetes mellitus.

The impact of obesity on cognitive function in patients with type 2 diabetes mellitus (T2DM) remains controversial. This study aimed to evaluate whether obesity, assessed by body mass index (BMI) was associated with cognitive function among T2DM patients and whether the effect of obesity on cognitive function was through brain structure. This was a post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) study. The cognitive test battery included the Digit Symbol Substitution Test (DSST), Mini-Mental State Exam (MMSE), Rey Auditory Verbal Learning Test (RAVLT), and STROOP test, which were administered at baseline, and at 20, 40, and 80 months. A subgroup (n = 614) of the ACCORD-MIND study underwent MRI scanning at baseline and at 40 and 80 months. The total brain volume (TBV), abnormal white matter volume (AWM), abnormal gray matter volume (AGM), and abnormal basal ganglia volume (ABG) were estimated. The outcomes of this study were cognitive function and brain structure. In the adjusted analyses, BMI was positively associated with the MMSE (β:0.08, 95%CI,0.01-0.16, per standard deviation [SD] increase) and RAVLT scores (β:0.09, 95%CI,0.01-0.18). It was also associated with a greater TBV (β:7.48, 95%CI,0.29-14.67). BMI was not associated with the DSST or STROOP scores, and AWM, AGM, ABG. Mediation analysis found that the effect of BMI on MMSE/RAVLT was mediated through TBV. Obesity may be associated with greater cognitive function and the effect of BMI on cognitive function may be mediated by TBV among patients with T2DM. http://www.clinicaltrials.gov, identifier NCT00000620.

Association of Early Adulthood 25-Year Blood Pressure Trajectories With Cerebral Lesions and Brain Structure in Midlife

Midlife elevated blood pressure (BP) is an important risk factor associated with brain structure and function. Little is known about trajectories of BP that modulate this risk. To identify BP trajectory patterns from young adulthood to midlife that are associated with brain structure in midlife. This cohort study used data of US adults from Coronary Artery Risk Development in Young Adults (CARDIA), a prospective longitudinal study of Black and White men and women (baseline age 18 to 30 years) examined up to 8 times over 30 years (1985-1986 to 2015-2016). There were 885 participants who underwent brain magnetic resonance imaging (MRI) in the 25th or 30th year examinations. Analyses were conducted November 2019 to December 2020. Using group-based trajectory modeling, 5 25-year BP trajectories for 3 BP traits were identified in the total CARDIA cohort of participants with 3 or more BP measures, which were then applied to analyses of the subset of 853 participants in the Brain MRI substudy. Mean arterial pressure (MAP) was examined as an integrative measure of systolic and diastolic BP. With linear regression, the associations of the BP trajectories with brain structures were examined, adjusting sequentially for demographics, cardiovascular risk factors, and antihypertensive medication use. Brain MRI outcomes include total brain, total gray matter, normal-looking and abnormal white matter volumes, gray matter cerebral blood flow, and white matter fractional anisotropy. Brain MRI analyses were conducted on 853 participants (mean [SD] age, 50.3 [3.6] years; 399 [46.8%] men; 354 [41.5%] Black and 499 [58.5%] White individuals). The MAP trajectory distribution was 187 individuals (21.1%) with low-stable, 385 (43.5%) with moderate-gradual, 71 (8.0%) with moderate-increasing, 204 (23.1%) with elevated-stable, and 38 (4.3%) with elevated-increasing. Compared with the MAP low-stable trajectory group, individuals in the moderate-increasing and elevated-increasing groups were more likely to have higher abnormal white matter volume (moderate: β, 0.52; 95% CI, 0.23 to 0.82; elevated: β, 0.57; 95% CI, 0.19 to 0.95). Those in the MAP elevated-increasing group had lower gray matter cerebral blood flow (β, -0.42; 95% CI, -0.79 to -0.05) after adjusting for sociodemographics and cardiovascular risk factors. After adjustment for antihypertensive medication use, the difference was consistent for abnormal white matter volume, but results were no longer significant for gray matter cerebral blood flow. Among young adults with moderate to high levels of BP, a gradual increase in BP to middle-age may increase the risk in diffuse small vessel disease and lower brain perfusion.

Central network changes in patients with advanced monocular blindness: A voxel-based morphometric study.

ObjectiveTo study the changes in gray matter volume (GMV) in patients with advanced monocular blindness (MB) using voxel‐based morphometry (VBM).MethodsThirty‐one patients with advanced MB (25 males and six females) and 31 normal controls (25 males and six females) were enrolled. The t test was applied to determine the differences in GMV, white matter volume (WMV), and volume of cerebrospinal fluid in different regions of the brain. The local characteristics of spontaneous concentrations of brain tissue were evaluated by the VBM method. The effects of blindness duration on differences in the GMV were evaluated by correlation and regression analyses.ResultsCompared with the control group, the GMV was decreased in the upper right margin, bilateral insular cortex, right cingulate gyrus, left occipital gyrus, and right suboccipital lobe, and negatively correlated with blindness duration in the upper right posterior margin, bilateral insular cortex, and right cingulate cortex.ConclusionsWe found that patients with MB showed abnormal WMV and GMV, as evidenced by local changes in the brain. In addition, reduced GMV in specific parts of the brain was associated with the duration of blindness, which may indicate neuropathological mechanisms of visual loss in patients with MB.

Regional white matter volume abnormalities in first-episode somatization disorder.

Alterations of white matter integrity have been implicated in patients with somatization disorder (SD). However, changes of white matter volume (WMV) remain unclear. This study is designed to examine regional WMV in patients with SD and to investigate the potential relationships between WMV abnormalities and personality traits, cognitive function, and symptom severity. We recruited 25 first-episode, drug-naive patients with SD and 28 sex-, age-, and education-matched healthy controls for the study. Personality traits, cognitive function, and symptom severity were assessed for all participants. Data were analyzed with the computational anatomy toolbox (CAT12) methods. Patients with SD exhibited a significantly increased WMV in the right inferior frontal gyrus (IFG) (t = 4.4009) and a significantly decreased WMV in the left inferior longitudinal fasciculus (ILF) (t = -3.4292) relative to healthy controls. No correlation was found between abnormal WMV and clinical/cognitive variables in the patients. Our findings suggest the presence of significant regional WMV abnormalities in first-episode, drug-naive patients with SD, which might improve understanding the pathophysiology of SD.

Voxel-based meta-analysis of gray and white matter volume abnormalities in spinocerebellar ataxia type 2.

ObjectiveTo identify the consistent findings from the whole‐brain voxel‐based morphometry (VBM) studies on spinocerebellar ataxia type 2 (SCA2).MethodsThe whole‐brain VBM studies comparing SCA2 patients and healthy controls (HCs) were systematically searched in PubMed, Embase databases from January 2000 to June 2017. The coordinates with significant differences in gray matter (GM) and white matter (WM) between SCA2 patients and HCs were extracted separately from each cluster. A meta‐analysis was performed using anisotropic effect size‐based signed differential mapping (AES‐SDM) software.ResultsA total of five studies with 65 SCA2 patients and 124 HCs were included in the GM meta‐analysis. Four of the five studies with 50 SCA2 patients and 109 HCs were included in the WM meta‐analysis. Significant and consistent GM volume reductions were detected in bilateral cerebellar hemispheres, cerebellar vermis, the right fusiform gyrus, the right parahippocampal gyrus, and the right lingual gyrus. The WM volume reductions were observed in bilateral cerebellar hemispheres, cerebellar vermis, middle cerebellar peduncles, pons, and bilateral cortico‐spinal projections. The findings of the study remained largely unchanged in jackknife sensitivity analysis.ConclusionsThe consistent findings from our meta‐analysis showed that GM volume reductions in SCA2 patients were not limited in cerebellum while significant WM volume reductions widely existed in cerebellum and pyramidal system. The findings provide morphological basis for further studies on SCA2.

Cardiovascular health in young adulthood and structural brain MRI in midlife: The CARDIA study.

To examine the association between the American Heart Association (AHA) Life's Simple 7 (LS7) metric and brain structure. We determined cardiovascular health (CVH) according to the AHA LS7, assigning 0, 1, or 2 points for meeting poor, intermediate, or ideal criteria for the 7 components (range 0-14) at baseline (aged 18-30 years in 1985-1986) and year 25 follow-up examination for 518 participants of the Coronary Artery Risk Development in Young Adults (CARDIA) brain MRI substudy. Visit-based CVH score and average score was assessed in relation to percent of intracranial volume of normal tissue of the whole brain, gray matter, and white matter, and abnormal tissue volume of white matter at year 25 using multivariable linear, logistic, and quantile regression, after adjustment for age, sex, race, field center, educational attainment, and alcohol consumption. Mean percentage of whole brain volume, normal gray matter, and normal white matter was 81.3% (±2.5), 42.9% (±2.0), and 38.4% (±2.0). Greater CVH score at baseline (per each additional point at year 0: 0.1%, 95% confidence limits 0.01-0.3; p < 0.05) and average CVH score were associated with greater percentage of whole brain volume (per each additional point in average score: 0.2%, 95% confidence limits 0.04-0.3; p < 0.05). Visit-based or average CVH score was not significantly associated with normal gray or white matter volume or abnormal white matter volume. Maintaining ideal levels of cardiovascular health, determined by the LS7, in young adulthood is associated with greater whole brain volume in middle age but not regional differences in structure.

Cognitive Function and Kidney Disease: Baseline Data From the Systolic Blood Pressure Intervention Trial (SPRINT)

Chronic kidney disease is common and is associated with cardiovascular disease, cerebrovascular disease, and cognitive function, although the nature of this relationship remains uncertain. Cross-sectional cohort using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT). Participants in SPRINT, a randomized clinical trial of blood pressure targetsinolder community-dwelling adults with cardiovascular disease, chronic kidney disease, or high cardiovascular disease risk and without diabetes or known stroke, who underwent detailed neurocognitive testing in the cognition substudy, SPRINT-Memory and Cognition in Decreased Hypertension (SPRINT-MIND). Urine albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). Cognitive function, a priori defined as 5 cognitive domains based on 11 cognitive tests using zscores, and abnormal white matter volume quantified by brain magnetic resonance imaging. Of 9,361 SPRINT participants, 2,800 participated in SPRINT-MIND and 2,707 had complete data; 637 had brain imaging. Mean age was 68 years, 37% were women, 30% were black, and 20% had known cardiovascular disease. Mean eGFR was 70.8±20.9mL/min/1.73m2 and median urine ACR was 9.7 (IQR, 5.7-22.5) mg/g. In adjusted analyses, higher ACR was associated with worse global cognitive function, executive function, memory, and attention, such that each doubling of urine ACR had the same association with cognitive performance as being 7, 10, 6, and 14 months older, respectively. Lower eGFR was independently associated with worse global cognitive function and memory. In adjusted models, higher ACR, but not eGFR, was associated with larger abnormal white matter volume. Cross-sectional only, no patients with diabetes were included. In older adults, higher urine ACR and lower eGFR have independent associations with global cognitive performance with different affected domains. Albuminuria concurrently identifies a higher burden of abnormal brain white matter disease, suggesting that vascular disease may mediate these relationships.

Whole brain volume changes and its correlation with clinical symptom severity in patients with schizophrenia: A DARTEL-based VBM study.

The purpose of this study was to evaluate gray matter (GM) and white matter (WM) volume alterations in whole-brain structures in patients with schizophrenia and healthy controls using voxel-based morphometry (VBM), and further to assess the correlation between GM and WM volume variations and symptom severity in schizophrenia. A total of 22 patients with schizophrenia and 22 age-matched healthy controls participated. Magnetic resonance image data were processed using SPM8 software with diffeomorphic anatomical registration via an exponentiated Lie algebra (DARTEL) algorithm. Patients with schizophrenia exhibited significantly decreased GM volumes of the insula, superior temporal gyrus (STG), gyrus rectus, and anterior cingulate cortex (ACC) compared with healthy controls. The GM volumes of the STG and gyrus rectus were negatively correlated with the positive scales on the Positive and Negative Syndrome Scale (PANSS) and those of the STG and ACC were negatively correlated with the negative scales. The durations of illness in schizophrenia were negatively correlated with the GM volumes of the insula, STG, and ACC. Patients with schizophrenia exhibited significantly decreased WM volumes of the superior frontal gyrus, inferior temporal gyrus, and STG. The WM volumes of the STG were negatively correlated with the duration of illness. Our findings suggest that GM and WM volume abnormalities in the STG are associated with the psychopathology of schizophrenia.

Abstract P063: Cigarette Smoking and Neuroimaging Indices of Cerebrovascular Health in a Population-based Cohort of Middle-aged Adults

Introduction: Several studies report an association between cigarette smoking and dementia. One proposed hypothesis is that smoking leads to adverse cognitive and brain changes through vascular pathways. To date, few data exist on the link between smoking and vascular brain measures. We examined, in a population-based middle-aged cohort, the association of history of cigarette smoking with three indicators of cerebrovascular health: (i) white matter (WM) integrity measured using WM-fractional anisotropy, (ii) abnormal WM volume, and (iii) cerebral blood flow (CBF) in the gray matter. We focused on lobar measures of these indicators to detect whether specific regional cerebrovascular indicators are differently related to smoking. Hypothesis: We assessed the hypothesis that smoking history is associated with more adverse cerebrovascular measures (lower fractional anisotropy, larger abnormal WM volumes, and lower CBF). Methods: Data come from the Coronary Artery Risk Development in Young Adults CARDIA-brain magnetic resonance imaging sub-study (n=538). Brain measures and self-reported smoking history were obtained at the 25th year follow-up (mean age=50). We used linear (for CBF and WM-fractional anisotropy) and multinomial logistic (for abnormal WM volume) regression models, adjusted for potential confounders (including vascular and lifestyle risk factors and medical conditions). Results: Compared to never-smokers, current smokers had lower WM-fractional anisotropy in all brain lobes (-0.005 lower fractional anisotropy in the occipital lobe and -0.006 in the other lobes; p&lt;0.05). Smoking history was also associated with larger abnormal WM volumes: Compared to never-smokers, smokers and/or former-smokers had patterns of larger abnormal WM volumes in all lobes, with pronounced associations observed in the frontal lobe wherein smokers and former-smokers had up to twice the risk of having larger abnormal frontal WM volumes as never-smokers (p&lt;0.05). Smoking history was associated with lower CBF in the occipital (-2.89 ml/100g/min (95%CI=-5.43, -0.36); p=0.03) and parietal lobes (-3.31 (95%CI=-5.91, -0.71); p=0.01). Conclusions: In this cohort of middle-aged adults, associations between smoking and adverse WM measures were observed in all brain lobes, whereas associations of smoking with CBF were localized in the occipital and parietal lobes. This localization may reflect a link between smoking and blood flow processes related to sensory-cognitive networks. In conclusion, results suggest that smoking is associated with three early-indicators of cerebrovascular burden (WM-fractional anisotropy, WM abnormal volume, and CBF) across the brain and that it may be differentially related to different regional cerebrovascular indicators.

Chronic kidney disease, cerebral blood flow, and white matter volume in hypertensive adults.

To determine the relation between markers of kidney disease-estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR)-with cerebral blood flow (CBF) and white matter volume (WMV) in hypertensive adults. We used baseline data collected from 665 nondiabetic hypertensive adults aged ≥50 years participating in the Systolic Blood Pressure Intervention Trial (SPRINT). We used arterial spin labeling to measure CBF and structural 3T images to segment tissue into normal and abnormal WMV. We used quantile regression to estimate the association between eGFR and UACR with CBF and abnormal WMV, adjusting for sociodemographic and clinical characteristics. There were 218 participants (33%) with eGFR <60 mL/min/1.73 m(2) and 146 participants (22%) with UACR ≥30 mg/g. Reduced eGFR was independently associated with higher adjusted median CBF, but not with abnormal WMV. Conversely, in adjusted analyses, there was a linear independent association between UACR and larger abnormal WMV, but not with CBF. Compared to participants with neither marker of CKD (eGFR ≥60 mL/min/1.73 m(2) and UACR <30 mg/g), median CBF was 5.03 mL/100 g/min higher (95% confidence interval [CI] 0.78, 9.29) and abnormal WMV was 0.63 cm(3) larger (95% CI 0.08, 1.17) among participants with both markers of CKD (eGFR <60 mL/min/1.73 m(2) and UACR ≥30 mg/g). Among nondiabetic hypertensive adults, reduced eGFR was associated with higher CBF and higher UACR was associated with larger abnormal WMV.

Brain MRI Volume Findings in Diabetic Adults With Albuminuria: The ACCORD-MIND Study.

Albuminuria is associated with cognitive impairment in people with type 2 diabetes mellitus (T2DM). The brain volume correlates of albuminuria in people with T2DM have not been well investigated. We examined 502 individuals with T2DM (9-12 years duration; mean age ~62 years) who had a brain MRI at baseline and at 40 months. Baseline MRI findings were examined by the presence or absence of albuminuria (≥30mg/g creatinine). Changes in MRI findings were examined by whether albuminuria was persistent, intermittent, or absent during follow-up. At baseline, participants with albuminuria (28.7% of the cohort) had more abnormal white matter volume (AWMV) than participants without albuminuria on unadjusted analysis. This difference was attenuated with adjustment for systolic blood pressure, which was higher in participants with albuminuria than in those without albuminuria. During ~3.5 years of follow-up, participants with persistent albuminuria (15.8%) had a greater increase in new AWMV than participants without albuminuria (59.8%) or those with intermittent albuminuria on unadjusted analysis. This difference was attenuated with adjustment for age and systolic blood pressure. There were no significant differences in gray matter volume and total brain volume between participants with or without albuminuria at baseline or during follow-up. There was no significant effect modification of these findings by estimated glomerular filtration rate (eGFR) at baseline or change in eGFR during follow-up. In this diabetic cohort, baseline albuminuria and persistent albuminuria were not independently associated with any significant differences in brain volume measurements compared with participants without albuminuria.

Gray and white matter volume abnormalities in generalized anxiety disorder by categorical and dimensional characterization

Increasing efforts have been made to investigate the underlying pathophysiology of generalized anxiety disorder (GAD), but only limited consistent information is available on gray (GM) and white matter (WM) volume changes in affected adults. Additionally, few studies employed dimensional approaches to GAD pathology. This study compares structural brain imaging data from n=19 GAD subjects and n=24 healthy comparison (HC) subjects, all medication-free and matched on age, sex and education. Separate categorical and dimensional models were employed using voxel-based morphometry for GM and WM. Significantly higher GM volumes were found in GAD subjects mainly in basal ganglia structures and less consistently in the superior temporal pole. For WM, GAD subjects showed significantly lower volumes in the dlPFC. Largely consistent findings in dimensional and categorical models point toward these structural alterations being reliable and of importance for GAD. While lower volume in the dlPFC could reflect impaired emotional processing and control over worry in GAD, basal ganglia alterations may be linked to disturbed gain and loss anticipation as implicated in previous functional GAD studies. As perturbations in anticipation processes are central to GAD, these areas may warrant greater attention in future studies.

Brain white matter volume abnormalities in Lesch-Nyhan disease and its variants.

We sought to examine brain white matter abnormalities based on MRI in adults with Lesch-Nyhan disease (LND) or an attenuated variant (LNV) of this rare, X-linked neurodevelopmental disorder of purine metabolism. In this observational study, we compared 21 adults with LND, 17 with LNV, and 33 age-, sex-, and race-matched healthy controls using voxel-based morphometry and analysis of covariance to identify white matter volume abnormalities in both patient groups. Patients with classic LND showed larger reductions of white (26%) than gray (17%) matter volume relative to healthy controls. Those with LNV showed comparable reductions of white (14%) and gray (15%) matter volume. Both patient groups demonstrated reduced volume in medial inferior white matter regions. Compared with LNV, the LND group showed larger reductions in inferior frontal white matter adjoining limbic and temporal regions and the motor cortex. These regions likely include such long association fibers as the superior longitudinal and uncinate fasciculi. Despite earlier reports that LND primarily involves the basal ganglia, this study reveals substantial white matter volume abnormalities. Moreover, white matter deficits are more severe than gray matter deficits in classic LND, and also characterize persons with LNV. The brain images acquired for these analyses cannot precisely localize white matter abnormalities or determine whether they involve changes in tract orientation or anisotropy. However, clusters of reduced white matter volume identified here affect regions that are consistent with the neurobehavioral phenotype.

The cross-sectional and longitudinal associations of diabetic retinopathy with cognitive function and brain MRI findings: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

OBJECTIVELongitudinal evidence linking diabetic retinopathy with changes in brain structure and cognition is sparse. We used data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to determine whether diabetic retinopathy at baseline predicted changes in brain structure or cognition 40 months later.RESEARCH DESIGN AND METHODSParticipants from the ACCORD-MIND and ACCORD-Eye substudies were included in analyses of cognition (n = 1,862) and MRI-derived brain variables (n = 432). Retinopathy was categorized as none, mild nonproliferative, or moderate/severe. Tests of cognition included the Mini-Mental State Examination (MMSE), Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test, and Stroop test. Primary brain outcomes were gray matter and abnormal white matter volumes.RESULTSBaseline retinopathy was associated with lower gray matter volume (adjusted means of 470, 466, and 461 cm3 for none, mild, and moderate/severe retinopathy, respectively; P = 0.03). Baseline retinopathy also predicted a greater change in MMSE and DSST scores at 40 months in each retinopathy category (MMSE: −0.20, −0.57, and −0.42, respectively [P = 0.04]; DSST: −1.30, −1.84, and −2.89, respectively[P = 0.01]).CONCLUSIONSDiabetic retinopathy is associated with future cognitive decline in people with type 2 diabetes. Although diabetic retinopathy is not a perfect proxy for diabetes-related brain and cognitive decline, patients with type 2 diabetes and retinopathy represent a subgroup at higher risk for future cognitive decline.

The association of white matter volume in psychotic disorders with genotypic variation in NRG1, MOG and CNP: a voxel-based analysis in affected individuals and their unaffected relatives

We investigated the role of variation in putative psychosis genes coding for elements of the white matter system by examining the contribution of genotypic variation in three single-nucleotide polymorphisms (SNPs) neuregulin 1 (NRG1) SNP8NRG221533, myelin oligodendrocytes glycoprotein (MOG) rs2857766 and CNP (rs2070106) and one haplotype HAPICE (deCODE) to white matter volume in patients with psychotic disorder and their unaffected relatives. Structural magnetic resonance imaging and blood samples for genotyping were collected on 189 participants including patients with schizophrenia (SZ) or bipolar I disorder (BDI), unaffected first-degree relatives of these patients and healthy volunteers. The association of genotypic variation with white matter volume was assessed using voxel-based morphometry in SPM5. The NRG1 SNP and the HAPICE haplotype were associated with abnormal white matter volume in the BDI group in the fornix, cingulum and parahippocampal gyrus circuit. In SZ the NRG1 SNP risk allele was associated with lower white matter volume in the uncinate fasciculus (UF), right inferior longitudinal fasciculus and the anterior limb of the internal capsule. Healthy G-homozygotes of the MOG SNP had greater white matter volume in areas of the brainstem and cerebellum; this relationship was absent in those with a psychotic disorder and the unaffected relatives groups. The CNP SNP did not contribute to white matter volume variation in the diagnostic groups studied. Variation in the genes coding for structural and protective components of myelin are implicated in abnormal white matter volume in the emotion circuitry of the cingulum, fornix, parahippocampal gyrus and UF in psychotic disorders.

A voxel-based morphometry (VBM) analysis of regional grey and white matter volume abnormalities within the speech production network of children who stutter

It is well documented that neuroanatomical differences exist between adults who stutter and their fluently speaking peers. Specifically, adults who stutter have been found to have more grey matter volume (GMV) in speech relevant regions including inferior frontal gyrus, insula and superior temporal gyrus (Beal et al., 2007; Song et al., 2007). Despite stuttering having its onset in childhood only one study has investigated the neuroanatomical differences between children who do and do not stutter. Chang et al. (2008) reported children who stutter had less GMV in the bilateral inferior frontal gyri and middle temporal gyrus relative to fluently speaking children. Thus it appears that children who stutter present with unique neuroanatomical abnormalities as compared to those of adults who stutter. In order to better understand the neuroanatomical correlates of stuttering earlier in its development, near the time of onset, we used voxel-based morphometry to examine volumetric differences between 11 children who stutter and 11 fluent children. Children who stutter had less GMV in the bilateral inferior frontal gyri and left putamen but more GMV in right Rolandic operculum and superior temporal gyrus relative to fluent children. Children who stutter also had less white matter volume bilaterally in the forceps minor of the corpus callosum. We discuss our findings of widespread anatomic abnormalities throughout the cortical network for speech motor control within the context of the speech motor skill limitations identified in people who stutter (Namasivayam and van Lieshout, 2008; Smits-Bandstra et al., 2006).

Antidepressant Treatment Normalizes White Matter Volume in Patients with Major Depression

ObjectiveTo investigate white matter volume abnormalities in patients with major depression and the effects of antidepressant treatment on white matter volume.MethodMagnetic resonance imaging (MRI) was performed on 32 treatment-naïve depressed patients, 17 recovered patients who had received antidepressant treatment and subsequently achieved clinical recovery and 34 matched controls.ResultsRelative to the healthy controls, the treatment-naïve depressed patients showed increased white matter volumes in the left dorsolateral prefrontal cortex (DLPFC) and left putamen and reduced white matter volumes in the left cerebellum posterior lobe and left inferior parietal lobule. For the treatment-naïve patients, the length in months of the current depressive episode was positively correlated with the white matter volumes in both the left DLPFC and left putamen. In the recovered patients, the differences in white matter volume were no longer statistically significant relative to healthy controls. No significant difference was found in the total white matter volume among the three groups.ConclusionsThis study demonstrates that there were alterations in the white matter volumes of depressed patients, which might disrupt the neural circuits that are involved in emotional and cognitive function and thus contribute to the pathophysiology of depression. The finding of the significant correlations between refractoriness and the white matter volumes in the left DLPFC and left putamen combined with the finding that antidepressant treatment normalized the white matter volume of recovered patients, suggests that a quantitative, structural MRI measurement could act as a potential biomarker in depression therapy for individual subjects.

Structural Magnetic Resonance Imaging in Eating Disorders: A Systematic Review of Voxel‐Based Morphometry Studies

This systematic review summarises and critically appraises the literature on structural magnetic resonance imaging in people with a current or past eating disorder. Studies using voxel-based morphometry image analysis were included. Ten studies reported on a total of 236 people with a current or past eating disorder and 257 healthy controls. Sample heterogeneity prohibited a meta-analytic approach. The findings do not unequivocally indicate grey or white matter volume abnormalities in people with an eating disorder. Nevertheless, these preliminary data suggest that, compared with healthy controls, people with anorexia nervosa have decreased grey matter in a range of brain regions and that those with bulimia nervosa have increased grey matter volumes in frontal and ventral striatal areas. Research in the recovery phase and longitudinal studies suggest that potential brain tissue abnormalities may recover with clinical improvement. Overall, as the available data are inconclusive, further efforts in this field are warranted.

White matter alterations related to P300 abnormalities in individuals at high risk for psychosis: an MRI–EEG study

Psychosis onset is characterized by white matter and electrophysiologic abnormalities. The relation between these factors in the development of illness is almost unknown. We studied the relation between white matter volumes and P300 in prodromal psychosis. We assessed white matter volume (detected using magnetic resonance imaging) and electrophysiologic response during an oddball task (P300) in healthy controls and individuals at high clinical risk for psychosis (with an "at-risk mental state" [ARMS]). We included 41 controls and 39 patients with an ARMS in our study. A psychotic disorder developed in 26% of the ARMS group within the follow-up period of 2 years. The P300 amplitude was significantly lower in the ARMS group than in the control group. The ARMS group showed reduced volume of white matter underlying the left superior temporal gyrus and the left superior frontal gyrus and increased volume of white matter underlying the right insula and the right angular gyrus compared with controls. Relative to individuals who did not later become psychotic, the subgroup in whom psychosis subsequently developed had a smaller volume of white matter underlying the left precuneus and the right middle temporal gyrus and increased volume in the white matter underlying the right middle frontal gyrus. We observed a significant interaction in the right middle frontal gyrus: white matter volume was negatively associated with P300 amplitude in the ARMS group and positively associated with P300 amplitude in the control group. The voxel-based morphometry method alone cannot determine whether abnormal white matter volumes are due to an altered number of axonal connections or decreased myelination. P300 abnormalities precede the onset of psychosis and are directly related to white matter alterations, representing a correlate of an increased vulnerability to disease.