Abnormal anterior cingulum integrity in bipolar disorder determined through diffusion tensor imaging

Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA.
The British Journal of Psychiatry (Impact Factor: 7.99). 09/2008; 193(2):126-9. DOI: 10.1192/bjp.bp.107.048793
Source: PubMed


Convergent evidence implicates white matter abnormalities in bipolar disorder. The cingulum is an important candidate structure for study in bipolar disorder as it provides substantial white matter connections within the corticolimbic neural system that subserves emotional regulation involved in the disorder.
To test the hypothesis that bipolar disorder is associated with abnormal white matter integrity in the cingulum.
Fractional anisotropy in the anterior and posterior cingulum was compared between 42 participants with bipolar disorder and 42 healthy participants using diffusion tensor imaging.
Fractional anisotropy was significantly decreased in the anterior cingulum in the bipolar disorder group compared with the healthy group (P=0.003); however, fractional anisotropy in the posterior cingulum did not differ significantly between groups.
Our findings demonstrate abnormalities in the structural integrity of the anterior cingulum in bipolar disorder. They extend evidence that supports involvement of the neural system comprising the anterior cingulate cortex and its corticolimbic gray matter connection sites in bipolar disorder to implicate abnormalities in the white matter connections within the system provided by the cingulum.

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Available from: Gaolang Gong, Mar 26, 2015
    • "The inclusion of severely chronic ill patients prevented us from establishing a drug wash-out period because of obvious ethical concerns. The effects of treatment on white-matter microstructure have not been well established yet; several studies have not reported a clear influence (McIntosh et al. 2008; Wang et al. 2008; Sussmann et al. 2009) but some evidence suggests that medication might even attenuate FA abnormalities in certain patients (Yoo et al. 2007; Versace et al. 2008). Even though, we included an established index of medication load (Sackeim, 2001; Almeida et al. 2009) in the analyses to control for the potential confounding effects, and the results remained unaltered. "
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    ABSTRACT: Although white-matter abnormalities have been reported in middle-aged patients with major depressive disorder (MDD), few data are available on treatment-resistant MDD and the influence of relevant variables related to clinical burden of illness is far from being well established. The present study examined white-matter microstructure in a sample of 52 patients with MDD in different stages (treatment-resistant/chronic MDD, n = 18; remitted-recurrent MDD, n = 15; first-episode MDD, n = 19) and 17 healthy controls, using diffusion tensor imaging with a tract-based spatial statistics approach. Groups were comparable in age and gender distribution, and results were corrected for familywise error (FWE) rate. Widespread significant reductions of fractional anisotropy (FA) - including the cingulum, corpus callosum, superior and inferior longitudinal fascicule - were evident in treatment-resistant/chronic MDD compared with first-episode MDD and controls (p < 0.05, FWE-corrected). Decreased FA was observed within the ventromedial prefrontal region in treatment-resistant/chronic MDD even when compared with the remitted-recurrent MDD group (p < 0.05, FWE-corrected). Longer duration of illness (β = -0.49, p = 0.04) and higher depression severity (at a trend level: β = -0.26, p = 0.06) predicted lower FA in linear multiple regression analysis at the whole-brain level. The number of previous episodes and severity of symptoms were significant predictors when focused on the ventromedial prefrontal area (β = -0.28, p = 0.04; and β = -0.29, p = 0.03, respectively). Medication effects were controlled for in the analyses and results remained unaltered. Our findings support the notion that disruptions of white-matter microstructure, particularly in fronto-limbic networks, are associated with resistance to treatment and higher current and past burden of depression.
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    • "To date most investigations of microstructural white matter changes in patients with BD have been conducted in patients who are in mid-life or who have persistent or recurrent disorders [1], [5]–[8]. These studies have identified a wide range of abnormalities including structural changes within the CC, cingulate as well as the inferior and superior longitudinal fasciculi [1],[5],[7],[8]. Moreover, a recent meta-analysis of diffusion tension studies [9] suggests two clusters of abnormality (on the right parahippocampal gyrus and subgenual cingulate cortex). "
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    ABSTRACT: To date, most studies of white matter changes in Bipolar Disorder (BD) have been conducted in older subjects and with well-established disorders. Studies of young people who are closer to their illness onset may help to identify core neurobiological characteristics and separate these from consequences of repeated illness episodes or prolonged treatment. Diffusion tensor imaging (DTI) was used to examine white matter microstructural changes in 58 young patients with BD (mean age 23 years; range 16-30 years) and 40 controls. Whole brain voxelwise measures of fractional anisotropy (FA), parallel diffusivity (λ//) and radial diffusivity (λ⊥) were calculated for all subjects. White matter microstructure differences (decreased FA corrected p<.05) were found between the patients with BD and controls in the genu, body and splenium of the corpus callosum as well as the superior and anterior corona radiata. In addition, significantly increased radial diffusivity (p<.01) was found in the BD group. Neuroimaging studies of young patients with BD may help to clarify neurodevelopmental aspects of the illness and for identifying biomarkers of disease onset and progression. Our findings provide evidence of microstructural white matter changes early in the course of illness within the corpus callosum and the nature of these changes suggest they are associated with abnormalities in the myelination of axons.
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    • "Various methods of analyzing DTI data have been developed based on this technique. DTI studies using the region of interest (ROI) approach have reported reduced FA within adult patients in prefrontal WM, corpus callosum (Macritchie et al., 2010; Wang et al., 2008b), anterior cingulum (Wang et al., 2008a), anterior limb of the internal capsule (Sussmann et al., 2009), anterior thalamic radiation, and uncinate fasciculus (McIntosh et al., 2008). First-episode (FE) BD adolescents showed significantly decreased FA in superior-frontal WM tracts in one study (Adler et al., 2006), but another study showed increased FA in anterior frontal regions and corpus callosum and normal FA in several other regions (Heng et al., 2010). "
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    ABSTRACT: Structural abnormality of both gray and white matter has been detected in patients with bipolar disorder (BD). But results were greatly inconsistent across studies which were most likely attributed to heterogeneous populations as well as processing techniques. The present study aimed to investigate brain structural and microstructural alterations in a relative homogenous sample of bipolar mania. 3D T1-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were conducted in 18 patients with BD and 27 healthy volunteers. Gray matter (GM) and white matter (WM) differences were evaluated using voxel-based morphometry (VBM) and voxel-based analysis of fractional anisotropy (FA) maps derived from DTI, respectively. Patients with BD had a larger volume of GM in the left thalamus and bilateral basal ganglia, including the bilateral putamen and extending to the left claustrum, as well as reduced FA values in the left posterior corona radiata. By combined analysis, alterations in subcortical GM areas and part of the corresponding association fiber area were detected. Compared with observations in homogeneous samples, our findings indicate that disruption of the limbic network may be intrinsic to BD.
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