Progression of neuroanatomical abnormalities after first-episode of psychosis: A 3-year longitudinal sMRI study.

The location, extent and progression of longitudinal morphometric changes after first-episode of psychosis (FEP) remains unclear. We investigated ventricular and cortico-subcortical regions over a 3-year period in FEP patients compared with healthy controls. High resolution 1.5T T1-weighted MR images were obtained at baseline from 28 FEP patients at presentation and 28 controls, and again after 3-years. The longitudinal FreeSurfer pipeline (v.5.3.0) was used for regional volumetric and cortical reconstruction image analyses. Repeated-measures ANCOVA and vertex-wise linear regression analyses compared progressive changes between groups in subcortical structures and cortical thickness respectively. Compared with controls, patients displayed progressively reduced volume of the caudate [F (1,51)=5.86, p=0.02, Hedges' g=0.66], putamen [F (1,51)=6.06, p=0.02, g=0.67], thalamus [F (1,51)=6.99, p=0.01, g=0.72] and increased right lateral ventricular volume [F (1, 51)=4.03, p=0.05], and significantly increased rate of cortical thinning [F (1,52)=5.11, p=0.028)] at a mean difference of 0.84% [95% CI (0.10, 1.59)] in the left lateral orbitofrontal region over the 3-year period. In patients, greater reduction in putamen volume over time was associated with lower cumulative antipsychotic medication dose (r=0.49, p=0.01), and increasing lateral ventricular volume over time was associated with worsening negative symptoms (r=0.41, p=0.04) and poorer global functioning (r= -0.41, p=0.04). This study demonstrates localised progressive structural abnormalities in the cortico-striato-thalamo-cortical circuit after the onset of psychosis, with increasing ventricular volume noted as a neuroanatomical marker of poorer clinical and functional outcome.

Cognitive and Clinical Predictors of Prefrontal Cortical Thickness Change Following First-Episode of Psychosis.

The association of neuroanatomical progression with cognitive and clinical deterioration after first-episode of psychosis remains uncertain. This longitudinal study aims to assess whether i)impaired executive functioning and emotional intelligence at first presentation are associated with progressive prefrontal and orbitofrontal cortical thinning ii)negative symptom severity is linked to progressive prefrontal cortical thinning. 1.5T MRI images were acquired at baseline and after 3.5 years for 20 individuals with first-episode psychosis and 18 controls. The longitudinal pipeline of Freesurfer was employed to parcellate prefrontal cortex at two time points. Baseline cognitive performance was compared between diagnostic groups using MANCOVA. Partial correlations investigated relationships between cognition and negative symptoms at baseline and cortical thickness change over time. Patients displayed poorer performance than controls at baseline in working memory, reasoning/problem solving and emotional intelligence. In patients, loss of prefrontal and orbitofrontal thickness over time was predicted by impaired working memory and emotional intelligence respectively at baseline. Moreover, exploratory analyses revealed that the worsening of negative symptoms over time was significantly related to prefrontal cortical thinning. Results indicate that specific cognitive deficits at the onset of psychotic illness are markers of progressive neuroanatomical deficits and that worsening of negative symptoms occurs with prefrontal thickness reduction as the illness progresses.

A comparative study of segmentation techniques for the quantification of brain subcortical volume.

Manual tracing of magnetic resonance imaging (MRI) represents the gold standard for segmentation in clinical neuropsychiatric research studies, however automated approaches are increasingly used due to its time limitations. The accuracy of segmentation techniques for subcortical structures has not been systematically investigated in large samples. We compared the accuracy of fully automated [(i) model-based: FSL-FIRST; (ii) patch-based: volBrain], semi-automated (FreeSurfer) and stereological (Measure®) segmentation techniques with manual tracing (ITK-SNAP) for delineating volumes of the caudate (easy-to-segment) and the hippocampus (difficult-to-segment). High resolution 1.5 T T1-weighted MR images were obtained from 177 patients with major psychiatric disorders and 104 healthy participants. The relative consistency (partial correlation), absolute agreement (intraclass correlation coefficient, ICC) and potential technique bias (Bland-Altman plots) of each technique was compared with manual segmentation. Each technique yielded high correlations (0.77-0.87, p < 0.0001) and moderate ICC's (0.28-0.49) relative to manual segmentation for the caudate. For the hippocampus, stereology yielded good consistency (0.52-0.55, p < 0.0001) and ICC (0.47-0.49), whereas automated and semi-automated techniques yielded poor ICC (0.07-0.10) and moderate consistency (0.35-0.62, p < 0.0001). Bias was least using stereology for segmentation of the hippocampus and using FreeSurfer for segmentation of the caudate. In a typical neuropsychiatric MRI dataset, automated segmentation techniques provide good accuracy for an easy-to-segment structure such as the caudate, whereas for the hippocampus, a reasonable correlation with volume but poor absolute agreement was demonstrated. This indicates manual or stereological volume estimation should be considered for studies that require high levels of precision such as those with small sample size.

Age-Related Changes in Topological Degradation of White Matter Networks and Gene Expression in Chronic Schizophrenia.

Current hypotheses stipulate core symptoms of schizophrenia (SZ) result from the brain's incapacity to integrate neural processes. Converging diffusion magnetic resonance imaging and graph theory studies provide evidence of macrostructural alterations in SZ. However, age-related topological changes within and between white matter (WM) networks and its relationship to gene expression with disease progression remain incompletely understood. This cross-sectional study uses network modeling to investigate changes in WM network organization with disease progression in chronic SZ as well its relationship with gene expression in healthy brains. First, we replicate prior findings demonstrating altered global WM network topology in SZ. Novel results show significantly altered age-related network degradation patterns in patients compared with controls. Specifically, controls show stereotyped, linear global network decline with age. In contrast, patients show nonlinear network decline with age. Further analysis reveals lack of significant topological decline in younger adult patients, which is subsequently followed by stereotyped linear decline in older adult patients. Node-specific analyses show significant topological differences in frontal and limbic regions of younger adult patients compared with age-matched controls, which become less pronounced with age in older adult patients compared with age-matched controls. Lastly, we show several gene expression profiles, including DISC1, are associated with age-related changes in WM disconnectivity. Together, these findings provide novel WM topological and genetic evidence supporting neurodevelopmental models of SZ, suggesting that network remodeling continues throughout the third decade of life before stabilizing.

The Arcuate Fasciculus Network and Verbal Deficits in Psychosis.

BACKGROUND: Verbal learning (VL) and fluency (VF) are prominent cognitive deficits in psychosis, of which the precise neuroanatomical contributions are not fully understood. We investigated the arcuate fasciculus (AF) and its associated cortical regions to identify structural abnormalities contributing to these verbal impairments in early stages of psychotic illness. METHODS: Twenty-six individuals with recent-onset psychosis and 27 healthy controls underwent cognitive testing (MATRICS Consensus Cognitive Battery) and structural/diffusion-weighted MRI. Bilaterally, AF anisotropy and cortical thickness, surface area and volume of seven cortical regions were investigated in relation to VL and VF performance in both groups. RESULTS: Reduced right superior temporal gyrus surface area and volume related to better VF in controls. In psychosis, greater right pars opercularis volume and reduced left lateralization of this region related to better VL, while greater right long AF fractional anisotropy and right pars orbitalis volume related to better VF, these findings not present in controls. Psychosis had reduced right pars orbitalis thickness compared to controls. CONCLUSION: Anatomical substrates for normal processing of VL and VF appear altered in recent-onset psychosis. A possible aberrant role of the right hemisphere arcuate fasciculus and fronto-temporal cortical regions in psychosis may contribute to deficits in VL and VF.

Cognitive course in first-episode psychosis and clinical correlates: A 4 year longitudinal study using the MATRICS Consensus Cognitive Battery.

While cognitive impairments are prevalent in first-episode psychosis, the course of these deficits is not fully understood. Most deficits appear to remain stable, however there is uncertainty regarding the trajectory of specific cognitive domains after illness onset. This study investigates the longitudinal course of cognitive deficits four years after a first-episode of psychosis and the relationship of performance with clinical course and response to treatment. Twenty three individuals with psychotic illness, matched with 21 healthy volunteers, were assessed using the MATRICS Consensus Cognitive Battery at illness onset and 4 years later. We also investigated the relationship between cognitive deficits and quality of life and clinical indices. Verbal learning and two measures of processing speed had marked poorer trajectory over four years compared to the remaining cognitive domains. Processing speed performance was found to contribute to the cognitive deficits in psychosis. Poorer clinical outcome was associated with greater deficits at illness onset in reasoning and problem solving and social cognition. Cognitive deficits did not predict quality of life at follow-up, nor did diagnosis subtype differentiate cognitive performance. In conclusion, an initial psychotic episode may be associated with an additional cost on verbal learning and two measures of processing speed over a time spanning at least four years. Moreover, processing speed, which has been manipulated through intervention in previous studies, may represent a viable therapeutic target. Finally, cognition at illness onset may have a predictive capability of illness course.

Structural brain network analysis in families multiply affected with bipolar I disorder.

Disrupted structural connectivity is associated with psychiatric illnesses including bipolar disorder (BP). Here we use structural brain network analysis to investigate connectivity abnormalities in multiply affected BP type I families, to assess the utility of dysconnectivity as a biomarker and its endophenotypic potential. Magnetic resonance diffusion images for 19 BP type I patients in remission, 21 of their first degree unaffected relatives, and 18 unrelated healthy controls underwent tractography. With the automated anatomical labelling atlas being used to define nodes, a connectivity matrix was generated for each subject. Network metrics were extracted with the Brain Connectivity Toolbox and then analysed for group differences, accounting for potential confounding effects of age, gender and familial association. Whole brain analysis revealed no differences between groups. Analysis of specific mainly frontal regions, previously implicated as potentially endophenotypic by functional magnetic resonance imaging analysis of the same cohort, revealed a significant effect of group in the right medial superior frontal gyrus and left middle frontal gyrus driven by reduced organisation in patients compared with controls. The organisation of whole brain networks of those affected with BP I does not differ from their unaffected relatives or healthy controls. In discreet frontal regions, however, anatomical connectivity is disrupted in patients but not in their unaffected relatives.

Volume and shape analysis of subcortical brain structures and ventricles in euthymic bipolar I disorder.

Previous structural magnetic resonance imaging (S-MRI) studies of bipolar disorder have reported variable morphological changes in subcortical brain structures and ventricles. This study aimed to establish trait-related subcortical volumetric and shape abnormalities in a large, homogeneous sample of prospectively confirmed euthymic bipolar I disorder (BD-I) patients (n=60), compared with healthy volunteers (n=60). Participants were individually matched for age and gender. Volume and shape metrics were derived from manually segmented S-MR images for the hippocampus, amygdala, caudate nucleus, and lateral ventricles. Group differences were analysed, controlling for age, gender and intracranial volume. BD-I patients displayed significantly smaller left hippocampal volumes and significantly larger left lateral ventricle volumes compared with controls. Shape analysis revealed an area of contraction in the anterior head and medial border of the left hippocampus, as well as expansion in the right hippocampal tail medially, in patients compared with controls. There were no significant associations between volume or shape variation and lithium status or duration of use. A reduction in the head of the left hippocampus in BD-I patients is interesting, given this region's link to verbal memory. Shape analysis of lateral ventricular changes in patients indicated that these are not regionally specific.

Progressive Brain Atrophy and Cortical Thinning in Schizophrenia after Commencing Clozapine Treatment.

Despite evidence that clozapine may be neuroprotective, there are few longitudinal magnetic resonance imaging (MRI) studies that have specifically explored an association between commencement of clozapine treatment for schizophrenia and changes in regional brain volume or cortical thickness. A total of 33 patients with treatment-resistant schizophrenia and 31 healthy controls matched for age and gender underwent structural MRI brain scans at baseline and 6-9 months after commencing clozapine. MRI images were analyzed using SIENA (Structural Image Evaluation, using Normalization, of Atrophy) and FreeSurfer to investigate changes over time in brain volume and cortical thickness respectively. Significantly greater reductions in volume were detected in the right and left medial prefrontal cortex and in the periventricular area in the patient group regardless of treatment response. Widespread further cortical thinning was observed in patients compared with healthy controls. The majority of patients improved symptomatically and functionally over the study period, and patients who improved were more likely to have less cortical thinning of the left medial frontal cortex and the right middle temporal cortex. These findings demonstrate on-going reductions in brain volume and progressive cortical thinning in patients with schizophrenia who are switched to clozapine treatment. It is possible that this gray matter loss reflects a progressive disease process irrespective of medication use or that it is contributed to by switching to clozapine treatment. The clinical improvement of most patients indicates that antipsychotic-related gray matter volume loss may not necessarily be harmful or reflect neurotoxicity.

Cortical thinning and caudate abnormalities in first episode psychosis and their association with clinical outcome.

First episode psychosis (FEP) has been associated with structural brain changes, largely identified by volumetric analyses. Advances in neuroimaging processing have made it possible to measure geometric properties that may identify subtle structural changes not appreciated by a measure of volume alone. In this study we adopt complementary methods of assessing the structural integrity of grey matter in FEP patients and assess whether these relate to patient clinical and functional outcome at 3 year follow-up. 1.5 Tesla T1-weighted Magnetic Resonance (MR) images were acquired for 46 patients experiencing their first episode of psychosis and 46 healthy controls. Cerebral cortical thickness and local gyrification index (LGI) were investigated using FreeSurfer software. Volume and shape of the hippocampus, caudate and lateral ventricles were assessed using manual tracing and spherical harmonics applied for shape description. A cluster of cortical thinning was identified in FEP compared to controls; this was located in the right superior temporal gyrus, sulcus, extended into the middle temporal gyrus (lateral temporal cortex - LTC). Bilateral caudate volumes were significantly lower in FEP relative to controls and the right caudate also displayed regions of shape deflation in the FEP group. No significant structural abnormalities were identified in cortical LGI or hippocampal or lateral ventricle volume/shape. Neither LTC nor caudate abnormalities were related to change in symptom severity or global functioning 3 years later. LTC and caudate abnormalities are present at the first episode of psychosis but do not appear to directly affect clinical or functional outcome.

The miR-137 schizophrenia susceptibility variant rs1625579 does not predict variability in brain volume in a sample of schizophrenic patients and healthy individuals.

The micro RNA 137 (miR-137) variant rs1625579 has been identified as a genome-wide significant risk variant for schizophrenia. miR-137 has an established role in neurodevelopment and may mediate cognitive dysfunction in schizophrenia. This role of miR-137 may be related to changes in brain morphology for risk-related genotypes; however this has not yet been delineated. Here we considered whether rs1625579 genotype was predictive of indices of brain structure in patients with schizophrenia and healthy controls. Structural magnetic resonance imaging (sMRI) data (i.e. 3T T1-TFE or 1.5T T1-MPRAGE) were acquired from 150 healthy controls and 163 schizophrenic patients. Two volumetric analyses that considered the impact of miR-137/rs1625579 genotype were carried out on sMRI data. In the first analysis, voxel based morphometry was employed to consider genotype-related variability in local grey and white matter across the entire brain volume. Our secondary analysis utilized the FIRST protocol in FSL to consider the volume of subcortical structures (i.e. bilateral accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus). Several brain regions in both analyses demonstrated the expected main effect of participant group (i.e. schizophrenics < controls), yet there were no regions where we observed an impact of rs1635579 genotype on brain volume. Our analyses suggest that the mechanism by which miR-137 confers risk for schizophrenia and impacts upon cognitive function may not be mediated by changes in local brain volume. However, it remains to be determined whether or not alternative measures of brain structure are related to these functions of miR-137.

Distribution of tract deficits in schizophrenia.

BACKGROUND: Gray and white matter brain changes have been found in schizophrenia but the anatomical organizing process underlying these changes remains unknown. We aimed to identify gray and white matter volumetric changes in a group of patients with schizophrenia and to quantify the distribution of white matter tract changes using a novel approach which applied three complementary analyses to diffusion imaging data. METHODS: 21 patients with schizophrenia and 21 matched control subjects underwent brain magnetic resonance imaging. Gray and white matter volume differences were investigated using Voxel-based Morphometry (VBM). White matter diffusion changes were located using Tract Based Spatial Statistics (TBSS) and quantified within a standard atlas. Tracts where significant regional differences were located were examined using fiber tractography. RESULTS: No significant differences in gray or white matter volumetry were found between the two groups. Using TBSS the schizophrenia group showed significantly lower fractional anisotropy (FA) compared to the controls in regions (false discovery rate <0.05) including the genu, body and splenium of the corpus callosum and the left anterior limb of the internal capsule (ALIC). Using fiber tractography, FA was significantly lower in schizophrenia in the corpus callosum genu (p = 0.003). CONCLUSIONS: In schizophrenia, white matter diffusion deficits are prominent in medial frontal regions. These changes are consistent with the results of previous studies which have detected white matter changes in these areas. The pathology of schizophrenia may preferentially affect the prefrontal-thalamic white matter circuits traversing these regions.

Structural neuroimaging correlates of allelic variation of the BDNF val66met polymorphism.

BACKGROUND: The brain-derived neurotrophic factor (BDNF) val66met polymorphism is associated with altered activity dependent secretion of BDNF and a variable influence on brain morphology and cognition. Although a met-dose effect is generally assumed, to date the paucity of met-homozygotes have limited our understanding of the role of the met-allele on brain structure. METHODS: To investigate this phenomenon, we recruited sixty normal healthy subjects, twenty in each genotypic group (val/val, val/met and met/met). Global and local morphology were assessed using voxel based morphometry and surface reconstruction methods. White matter organisation was also investigated using tract-based spatial statistics and constrained spherical deconvolution tractography. RESULTS: Morphological analysis revealed an "inverted-U" shaped profile of cortical changes, with val/met heterozygotes most different relative to the two homozygous groups. These results were evident at a global and local level as well as in tractography analysis of white matter fibre bundles. CONCLUSION: In contrast to our expectations, we found no evidence of a linear met-dose effect on brain structure, rather our results support the view that the heterozygotic BDNF val66met genotype is associated with cortical morphology that is more distinct from the BDNF val66met homozygotes. These results may prove significant in furthering our understanding of the role of the BDNF met-allele in disorders such as Alzheimer's disease and depression.

Altered interhemispheric and temporal lobe white matter microstructural organization in severe chronic schizophrenia.

Diffusion MRI investigations in schizophrenia provide evidence of abnormal white matter (WM) microstructural organization as indicated by reduced fractional anisotropy (FA) primarily in interhemispheric, left frontal and temporal WM. Using tract-based spatial statistics (TBSS), we examined diffusion parameters in a sample of patients with severe chronic schizophrenia. Diffusion MRI data were acquired on 19 patients with chronic severe schizophrenia and 19 age- and gender-matched healthy controls using a 64 gradient direction sequence, (b=1300 s/mm(2)) collected on a Siemens 1.5T MRI scanner. Diagnosis of schizophrenia was determined by Diagnostic and Statistical Manual for Mental Disorders 4th Edition (DSM-IV) Structured Clinical Interview for DSM disorder (SCID). Patients were treatment resistance, having failed to respond to at least two antipsychotic medications, and had prolonged periods of moderate to severe positive or negative symptoms. Analysis of diffusion parameters was carried out using TBSS. Individuals with chronic severe schizophrenia had significantly reduced FA with corresponding increased radial diffusivity in the genu, body, and splenium of the corpus callosum, the right posterior limb of the internal capsule, right external capsule, and the right temporal inferior longitudinal fasciculus. There were no voxels of significantly increased FA in patients compared with controls. A decrease in splenium FA was shown to be related to a longer illness duration. We detected widespread abnormal diffusivity properties in the callosal and temporal lobe WM regions in individuals with severe chronic schizophrenia who have not previously been exposed to clozapine. These deficits can be driven by a number of factors that are indistinguishable using in vivo diffusion-weighted imaging, but may be related to reduced axonal number or packing density, abnormal glial cell arrangement or function, and reduced myelin.

Regional increase of cerebral cortex thickness in juvenile myoclonic epilepsy.

The goal of this study was to characterize cerebral cortex thickness patterns in juvenile myoclonic epilepsy (JME). Surface-based morphometry (SBM) was applied to process brain magnetic resonance images acquired from 24 patients with JME and 40 healthy controls and quantify cerebral cortex thickness. Differences in cortical thickness between patients and controls were determined using generalized linear model (covariates: age and gender). In patients with JME, thickness increase was detected bilaterally within localized regions in the orbitofrontal and mesial frontal cortices. Such thickness patterns coexisted with significant bilateral reduction in thalamic volume. These findings confirm that the underlying mechanisms in JME are related to aberrant corticothalamic structure and indicate that frontal cortex abnormalities are possibly linked to regional increase in cerebral cortical thickness.

Grey and white matter abnormalities in temporal lobe epilepsy with and without mesial temporal sclerosis.

Temporal lobe epilepsy with (TLE-mts) and without (TLE-no) mesial temporal sclerosis display different patterns of cortical neuronal loss, suggesting that the distribution of white matter damage may also differ between the sub-groups. The purpose of this study was to examine patterns of white matter damage in TLE-mts and TLE-no and to determine if identified changes are related to neuronal loss at the presumed seizure focus. The 4 T diffusion tensor imaging (DTI) and T1-weighted data were acquired for 22 TLE-mts, 21 TLE-no and 31 healthy controls. Tract-based spatial statistics (TBSS) was used to compare fractional anisotropy (FA) maps and voxel-based morphometry (VBM) was used to identify grey matter (GM) volume atrophy. Correlation analysis was conducted between the FA maps and neuronal loss at the presumed seizure focus. In TLE-mts, reduced FA was identified in the genu, body and splenium of the corpus callosum, bilateral corona radiata, cingulum, external capsule, ipsilateral internal capsule and uncinate fasciculus. In TLE-no, FA decreases were identified in the genu, the body of the corpus callosum and ipsilateral anterior corona radiata. The FA positively correlated with ipsilateral hippocampal volume. Widespread extra-focal GM atrophy was associated with both sub-groups. Despite widespread and extensive GM atrophy displaying different anatomical patterns in both sub-groups, TLE-mts demonstrated more extensive FA abnormalities than TLE-no. The microstructural organization in the corpus callosum was related to hippocampal volume in both patients and healthy subjects demonstrating the association of these distal regions.

Heritability of subcortical volumetric traits in mesial temporal lobe epilepsy.

OBJECTIVES: We aimed to 1) determine if subcortical volume deficits are common to mesial temporal lobe epilepsy (MTLE) patients and their unaffected siblings 2) assess the suitability of subcortical volumetric traits as endophenotypes for MTLE. METHODS: MRI-based volume measurements of the hippocampus, amygdala, thalamus, caudate, putamen and pallidium were generated using an automated brain reconstruction method (FreeSurfer) for 101 unrelated 'sporadic' MTLE patients [70 with hippocampal sclerosis (MTLE+HS), 31 with MRI-negative TLE], 83 unaffected full siblings of patients and 86 healthy control subjects. Changes in the volume of subcortical structures in patients and their unaffected siblings were determined by comparison with healthy controls. Narrow sense heritability was estimated ipsilateral and contralateral to the side of seizure activity. RESULTS: MTLE+HS patients displayed significant volume deficits across the hippocampus, amygdala and thalamus ipsilaterally. In addition, volume loss was detected in the putamen bilaterally. These volume deficits were not present in the unaffected siblings of MTLE+HS patients. Ipsilaterally, the heritability estimates were dramatically reduced for the volume of the hippocampus, thalamus and putamen but remained in the expected range for the amygdala. MRI-negative TLE patients and their unaffected siblings showed no significant volume changes across the same structures and heritability estimates were comparable with calculations from a healthy population. CONCLUSIONS: The findings indicate that volume deficits for many subcortical structures in 'sporadic' MTLE+HS are not heritable and likely related to acquired factors. Therefore, they do not represent suitable endophenotypes for MTLE+HS. The findings also support the view that, at a neuroanatomical level, MTLE+HS and MRI-negative TLE represent two distinct forms of MTLE.

MRI-based brain structure volumes in temporal lobe epilepsy patients and their unaffected siblings: a preliminary study.

INTRODUCTION: Investigating the heritability of brain structure may be useful in simplifying complicated genetic studies in temporal lobe epilepsy (TLE). A preliminary study is presented to determine if volume deficits of candidate brain structures present at a higher rate in unaffected siblings than controls subjects. METHODS: T1-weighted MR images was acquired for 28 TLE patients, a same-sex unaffected sibling of 12 of these and 28 normal controls. Selected brain structure volumes were measured using an automated whole brain segmentation technique. Candidate brain structure endophenotypes were determined and group differences were investigated between (1) controls and patients and (2) controls and siblings. ICC's were used to measure the quantitative volumetric association within each sibling pair. RESULTS: TLE patients demonstrated a significantly lower cerebral white matter, bilateral hippocampus, thalamus, and left entorhinal cortex volumes when compared with controls. A significant deficit in cerebral white matter (CWM) was common to patient and nonaffected siblings when compared with controls. Furthermore, a significant correlation was revealed between patients and siblings in CWM and bilateral thalamus. CONCLUSION: The findings suggest an overlap in the neurodevelopmental genes responsible for both brain structure and the expression of the disease. Further work is ongoing to confirm these findings.