Limbic and callosal white matter changes in euthymic bipolar I disorder: an advanced diffusion magnetic resonance imaging tractography study.

White matter microstructural changes detected using diffusion tensor imaging have been reported in bipolar disorder. However, findings are heterogeneous, which may be related to the use of analysis techniques that cannot adequately model crossing fibers in the brain. We therefore sought to identify altered diffusion anisotropy and diffusivity changes using an improved high angular resolution fiber-tracking technique. Diffusion magnetic resonance imaging data was obtained from 35 prospectively confirmed euthymic bipolar disorder type 1 patients (age 22-59) and 43 control subjects (age 22-59) drawn from a sample of 120 age- and gender-matched demographically similar case-control pairs. Tractography using a constrained spherical deconvolution approach to account for crossing fibers was implemented. Changes in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity between patient and control groups in subdivisions of the corpus callosum, cingulum, and fornix were measured as indicators of trait differences in white matter microstructural organization in bipolar disorder. Patients had significantly reduced fractional anisotropy and increased mean diffusivity and radial diffusivity in all divisions of the corpus callosum, left fornix, and subgenual cingulum compared with control subjects. Axial diffusivity was increased in the fornix bilaterally and right dorsal-anterior cingulum. By using an improved fiber-tracking method in a clinically homogeneous population, we were able to localize trait diffusivity changes to specific subdivisions of limbic fiber pathways, including the fornix. Our findings extend previous reports of altered limbic system microstructural disorganization as a trait feature of bipolar disorder.

Emsell L ，Leemans A ，Langan C ，Van Hecke W ，Barker GJ ，McCarthy P ，Jeurissen B ，Sijbers J ，Sunaert S ，Cannon DM ，McDonald C ... -  《-》

Tract-specific analysis of white matter integrity disruption in schizophrenia.

Several studies have suggested that white matter integrity is disrupted in some brain regions in patients with schizophrenia. The purpose of this study was to assess the white matter integrity of the cingulum, uncinate fasciculus, fornix, and corpus callosum using diffusion tensor imaging (DTI). Participants comprised 39 patients with schizophrenia (19 males and 20 females) and 40 age-matched normal controls (20 males and 20 females). We quantitatively assessed the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of the anterior cingulum, body of the cingulum, uncinate fasciculus, fornix, and corpus callosum on a tract-specific basis using diffusion tensor tractography (DTT). Group differences in FA and ADC between the patients and normal controls were sought. Additional exploratory analyses of the relationship between the FA or ADC and four clinical parameters (i.e., illness duration, positive symptom scores, negative symptom scores, and medication dosage) were performed. Results were analyzed in gender-combined and gender-separated group comparisons. FA was significantly lower on both sides of the anterior cingulum, uncinate fasciculus, and fornix in the schizophrenia patients irrespective of gender group separation. In the gender-combined analyses, significantly higher ADC values were demonstrated in the schizophrenia patients in both sides of the anterior cingulum, body of the cingulum and uncinate fasciculus, the left fornix, and the corpus callosum, compared with those of the normal controls. In the gender-separated analyses, the male patients showed higher ADC in the left anterior cingulum, the bilateral cingulum bodies, and the bilateral uncinate fasciculi. The female patients showed higher ADC in the right anterior cingulum, the left fornix, and the bilateral uncinate fasciculus. In correlation analyses, a significant negative correlation was found between illness duration and ADC in the right anterior cingulum in the gender-combined analyses. The gender-separated analyses found that the male patients had a significant negative correlation between negative symptom scores and FA in the right fornix, a positive correlation between illness duration and FA in the right anterior cingulum, and a negative correlation between illness duration and FA in the left uncinate fasciculus. Our DTI study showed that the integrity of white matter is disrupted in patients with schizophrenia. The results of our sub-analyses suggest that changes in FA and ADC may be related to negative symptom scores or illness duration.

Kunimatsu N ，Aoki S ，Kunimatsu A ，Abe O ，Yamada H ，Masutani Y ，Kasai K ，Yamasue H ，Ohtomo K ... -  《PSYCHIATRY RESEARCH》

Microstructural white matter changes in euthymic bipolar patients: a whole-brain diffusion tensor imaging study.

Wessa M ，Houenou J ，Leboyer M ，Chanraud S ，Poupon C ，Martinot JL ，Paillère-Martinot ML ... -  《-》

Tract-specific white matter structural disruption in patients with bipolar disorder.

A growing body of evidence suggests that, independent of localized brain lesions, mood disorders can be associated with dysfunction of brain networks involved in the modulation of emotional and cognitive behavior. We used diffusion tensor (DT) tractography to quantify the presence and extent of structural injury to the connections between the amygdala and other brain regions, which included the subgenual, the supragenual and posterior cingulate, the parahippocampal, the orbitofrontal and dorsolateral prefrontal cortices, as well as the insula. Using a 3.0 Tesla scanner, conventional and DT magnetic resonance imaging sequences of the brain were acquired from 15 adult patients with major depressive disorder (MDD), 15 with bipolar disorder (BD), and 21 age-matched healthy controls. Using FSL software, diffusivity changes of the white matter (WM) fiber bundles belonging to the emotional network were measured. Compared to controls and MDD patients, BD patients had significantly decreased average fractional anisotropy, increased average mean diffusivity, and increased average axial and radial diffusivity values in the majority of the WM fiber bundles connecting structures of the anterior limbic network (p-values ranging from 0.002 to 0.040). Medication load did not influence the results with the exception of lithium, which was associated with normal diffusivity values in tracts connecting the amygdala with the subgenual cingulate cortex. We detected specific WM abnormalities, suggestive of disrupted integrity of fiber bundles in the brains of patients with BD. These abnormalities might contribute to understanding both mood dysregulation and cognitive disturbances in BD, and might provide an objective marker to monitor treatment efficacy in this condition.

Benedetti F ，Absinta M ，Rocca MA ，Radaelli D ，Poletti S ，Bernasconi A ，Dallaspezia S ，Pagani E ，Falini A ，Copetti M ，Colombo C ，Comi G ，Smeraldi E ，Filippi M ... -  《-》

White matter differences in euthymic bipolar I disorder: a combined magnetic resonance imaging and diffusion tensor imaging voxel-based study.

A broad range of subtle and markedly heterogenous neuroanatomical abnormalities of grey matter and white matter have been reported in bipolar disorder. Euthymic bipolar disorder patients represent a clinically homogenous group in which to identify trait-based biomarkers of bipolar disorder. In this study, we sought to clarify the nature and extent of neuroanatomical differences in a large, clinically homogeneous group of euthymic bipolar disorder patients. Structural magnetic resonance imaging (sMRI) was obtained for 60 patients with prospectively confirmed euthymic bipolar I disorder and 60 individually age- and gender-matched healthy volunteers. High angular resolution diffusion tensor imaging (DTI) scans were obtained for a subset of this sample comprising 35 patients and 43 controls. Voxel-based analysis of both sMRI and DTI data sets was performed. Bipolar disorder patients displayed global reductions in white matter volume and fractional anisotropy reductions in the corpus callosum, posterior cingulum, and prefrontal white matter compared with controls. There were corresponding increases in radial diffusivity in the callosal splenium in patients compared with controls. No significant group differences were detected in grey matter. In patients, lithium was associated with a bilateral increase in grey matter volume in the temporal lobes, but not with any DTI parameter. Euthymic bipolar I disorder is characterized by both diffuse global white matter deficits and potential regional disorganization in interhemispheric and longitudinal tracts, while grey matter appears to be preserved.

Emsell L ，Langan C ，Van Hecke W ，Barker GJ ，Leemans A ，Sunaert S ，McCarthy P ，Nolan R ，Cannon DM ，McDonald C ... -  《-》