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White matter abnormalities in bipolar disorder and schizophrenia detected using diffusion tensor magnetic resonance imaging Bipolar disorder (BD) is strongly associated with white matter abnormalities. Postmortem studies have revealed a reduction in glial cells in the subgenual prefrontal cortex (1) and there is evidence from T 2 -weighted magnetic resonance imaging (MRI) that patients with BD have an increase in white matter hyperintensities compared to healthy controls (2, 3). T 1 -weighted MRI has also revealed white matter reductions using both region of interest (ROI) (4, 5) and voxel-based morphometry (VBM) approaches (6).Conventional T 1 -weighted MRI is, however, limited in its ability to identify abnormalities of white matter, since the signal is largely dependent upon water content and is potentially confounded by non-neuronal tissue components. Diffusion tensor imaging (DTI) is a more recent technique that measures the diffusivity of water molecules within tissues in vivo. Yet there have been few DTI studies in BD and all of these have had relatively small sample sizes. Their findings have included Objectives: Strong qualitative and quantitative evidence exists of white matter abnormalities in both schizophrenia and bipolar disorder (BD). Diffusion tensor imaging (DTI) studies suggest altered connectivity in both disorders. We aim to address the diagnostic specificity of white matter abnormalities in these disorders.Methods: DTI was used to assess white matter integrity in clinically stable patients with familial BD (n = 42) and familial schizophrenia (n = 28), and in controls (n = 38). Differences in fractional anisotropy (FA) were measured using voxel-based morphometry and automated region of interest analysis.Results: Reduced FA was found in the anterior limb of the internal capsule (ALIC), anterior thalamic radiation (ATR), and in the region of the uncinate fasciculus in patients with BD and those with schizophrenia compared with controls. A direct comparison between patient groups found no significant differences in these regions. None of the findings were associated with psychotropic medication.Conclusions: Reduced integrity of the ALIC, uncinate fasciculus, and ATR regions is common to both schizophrenia and BD. These results imply an overlap in white matter pathology, possibly relating to risk factors common to both disorders.

Theories of abnormal anatomical and functional connectivity in schizophrenia and bipolar disorder are supported by evidence from functional magnetic resonance imaging (MRI), structural MRI and diffusion tensor imaging (DTI). The presence of similar abnormalities in unaffected relatives suggests such disconnectivity is genetically mediated, albeit through unspecified loci. Neuregulin 1 (NRG1) is a psychosis susceptibility gene with effects on neuronal migration, axon guidance and myelination that could potentially explain these findings. In the current study, unaffected subjects were genotyped at the NRG1 single nucleotide polymorphism (SNP) rs6994992 (SNP8NRG243177) locus, previously associated with increased risk for psychosis, and the effect of genetic variation at this locus on white matter density (T 1 -weighted MRI) and integrity (DTI) was ascertained. Subjects with the riskassociated TT genotype had reduced white matter density in the anterior limb of the internal capsule and evidence of reduced structural connectivity in the same region using DTI. We therefore provide the first imaging evidence that genetic variation in NRG1 is associated with reduced white matter density and integrity in human subjects. This finding is discussed in the context of NRG1 effects on neuronal migration, axon guidance and myelination.

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Pyrexia soon after stroke is associated with severe stroke and poor functional outcome. Few studies have assessed brain temperature after stroke in patients, so little is known of its associations with body temperature, stroke severity, or outcome. We measured temperatures in ischemic and normal-appearing brain using 1H-magnetic resonance spectroscopy and its correlations with body (tympanic) temperature measured four-hourly, infarct growth by 5 days, early neurologic (National Institute of Health Stroke Scale, NIHSS) and late functional outcome (death or dependency). Among 40 patients (mean age 73 years, median NIHSS 7, imaged at median 17 hours), temperature in ischemic brain was higher than in normal-appearing brain on admission (38.6°C-core, 37.9°C-contralateral hemisphere, P=0.03) but both were equally elevated by 5 days; both were higher than tympanic temperature. Ischemic lesion temperature was not associated with NIHSS or 3-month functional outcome; in contrast, higher contralateral normal-appearing brain temperature was associated with worse NIHSS, infarct expansion and poor functional outcome, similar to associations for tympanic temperature. We conclude that brain temperature is higher than body temperature; that elevated temperature in ischemic brain reflects a local tissue response to ischemia, whereas pyrexia reflects the systemic response to stroke, occurs later, and is associated with adverse outcomes.

BackgroundStructural Magnetic Resonance Imaging (sMRI) of the brain is employed in the assessment of a wide range of neuropsychiatric disorders. In order to improve statistical power in such studies it is desirable to pool scanning resources from multiple centres. The CaliBrain project was designed to provide for an assessment of scanner differences at three centres in Scotland, and to assess the practicality of pooling scans from multiple-centres.MethodsWe scanned healthy subjects twice on each of the 3 scanners in the CaliBrain project with T1-weighted sequences. The tissue classifier supplied within the Statistical Parametric Mapping (SPM5) application was used to map the grey and white tissue for each scan. We were thus able to assess within scanner variability and between scanner differences. We have sought to correct for between scanner differences by adjusting the probability mappings of tissue occupancy (tissue priors) used in SPM5 for tissue classification. The adjustment procedure resulted in separate sets of tissue priors being developed for each scanner and we refer to these as scanner specific priors.ResultsVoxel Based Morphometry (VBM) analyses and metric tests indicated that the use of scanner specific priors reduced tissue classification differences between scanners. However, the metric results also demonstrated that the between scanner differences were not reduced to the level of within scanner variability, the ideal for scanner harmonisation.ConclusionOur results indicate the development of scanner specific priors for SPM can assist in pooling of scan resources from different research centres. This can facilitate improvements in the statistical power of quantitative brain imaging studies.

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