Davis KA, Kwon A, Cardenas VA, Deicken RF. Decreased cortical gray and cerebral white matter in male patients with familial bipolar I disorder. J Affect Disord 82: 475-485

Psychiatry Service, Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
Journal of Affective Disorders (Impact Factor: 3.38). 12/2004; 82(3):475-85. DOI: 10.1016/j.jad.2004.03.010
Source: PubMed


Previous MRI studies of bipolar disorder have failed to consistently demonstrate cortical gray or cerebral white matter tissue loss, as well as sulcal or ventricular enlargement. The inconsistencies are most likely due to the clinical and gender heterogeneity of the study populations as well as the different MRI acquisition and processing techniques. The objective of this study was to determine if there was a cortical gray matter and cerebral white matter deficit as well as sulcal and ventricular enlargement in a homogeneous sample of euthymic male patients with familial bipolar I disorder.
MRI tissue segmentation was utilized to obtain cortical gray matter, cerebral white matter, ventricular cerebrospinal fluid (CSF), and sulcal CSF volumes in 22 euthymic males with familial bipolar I disorder and 32 healthy male control subjects.
Relative to the controls, the familial bipolar I patients demonstrated: (1) significant reductions of both cortical gray matter and cerebral white matter volumes; and (2) significant increases in both sulcal and ventricular CSF volumes. In the bipolar group, there was a significant negative correlation between cortical gray matter volume and sulcal CSF volume.
Small sample size, retrospective interviews, possible medication effects.
These results provide evidence for significant cortical gray matter and cerebral white matter deficits and associated sulcal and ventricular enlargement in euthymic males with familial bipolar I disorder.

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    • "This finding was consistent with most previous studies (Chen et al., 2007; Strakowski et al., 2005; Wilke et al., 2004), which included both men and women, as well as a meta-analysis of FE BD (Vita et al., 2009). However , one prior study has shown decreased GM or WM volume in male familial bipolar I patients (Davis et al., 2004). Our findings extend the previous results in a homogeneous population of relatively young, FE manic male patients with familial BD. "
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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.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 11/2011; 36(2):231-8. DOI:10.1016/j.pnpbp.2011.11.002 · 3.69 Impact Factor
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    • "Several lines of evidence suggest that abnormal white matter connectivity may be relevant to the pathophysiology of bipolar disorder. Traditional volumetric magnetic resonance imaging (MRI) studies report nonspecific white matter volume deficits (Strakowski et al. 2002; Kieseppa et al. 2003; Davis et al. 2004). "
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    ABSTRACT: Callosal volume reduction has been observed in patients with bipolar disorder, but whether these deficits reflect genetic vulnerability to the illness remains unresolved. Here, we used computational methods to map corpus callosum abnormalities in a population-based sample of twin pairs discordant for bipolar disorder. Twenty-one probands with bipolar I disorder (mean age 44.4 ± 7.5 years; 48% female), 19 of their non-bipolar co-twins, and 34 demographically matched control twin individuals underwent magnetic resonance imaging. Three-dimensional callosal surface models were created to visualize its morphologic variability and to localize group differences. Neurocognitive correlates of callosal area differences were additionally investigated in a subsample of study participants. Bipolar (BPI) probands, but not their co-twins, showed significant callosal thinning and area reduction, most pronounced in the genu and splenium, relative to healthy twins. Altered callosal curvature was additionally observed in BPI probands. In bipolar probands and co-twins, genu and splenium midsagittal areas were significantly correlated with verbal processing speed and response inhibition. These findings suggest that aberrant connections between cortical regions--possibly reflecting decreased myelination of white matter tracts--may be involved in bipolar pathophysiology. However, findings of callosal thinning appear to be disease related, rather than reflecting genetic vulnerability to bipolar illness.
    Cerebral Cortex 03/2011; 21(10):2415-24. DOI:10.1093/cercor/bhr030 · 8.67 Impact Factor
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    • "In particular, altered expression of oligodendrocyte and myelin genes (Tkachev et al, 2003) and a lower density of oligodendroglial (Uranova et al, 2004) and glial (Rajkowska et al, 2001) cells have been reported in the prefrontal cortex of patients compared to healthy volunteers. MRI studies reported less left hemisphere (Kieseppa et al, 2003) and whole brain (Strakowski et al, 1993; Davis et al, 2004) white matter volume in patients compared to healthy volunteers. Few studies have investigated regional differences in white matter using MRI, although Bruno and colleagues (2004) identified lower white matter density in frontostriatal regions in bipolar patients compared to healthy volunteers using voxel-based morphometry. "
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    ABSTRACT: There is evidence from post-mortem and magnetic resonance imaging studies that hyperintensities, oligodendroglial abnormalities, and gross white matter volumetric alterations are involved in the pathophysiology of bipolar disorder. There is also functional imaging evidence for a defect in frontal cortico-subcortical pathways in bipolar disorder, but the white matter comprising these pathways has not been well investigated. Few studies have investigated white matter integrity in patients with bipolar disorder compared to healthy volunteers and the majority of studies have used manual region-of-interest approaches. In this study, we compared fractional anisotropy (FA) values between 30 patients with bipolar disorder and 38 healthy volunteers in the brain white matter using a voxelwise analysis following intersubject registration to Talairach space. Compared to healthy volunteers, patients demonstrated significantly (p<0.001; cluster size > or =50) higher FA within the right and left frontal white matter and lower FA within the left cerebellar white matter. Examination of individual eigenvalues indicated that group differences in both axial diffusivity and radial diffusivity contributed to abnormal FA within these regions. Tractography was performed in template space on averaged diffusion tensor imaging data from all individuals. Extraction of bundles passing through the clusters that differed significantly between groups suggested that white matter abnormalities along the pontine crossing tract, corticospinal/corticopontine tracts, and thalamic radiation fibers may be involved in the pathogenesis of bipolar disorder. Our findings are consistent with models of bipolar disorder that implicate dysregulation of cortico-subcortical and cerebellar regions in the disorder and may have relevance for phenomenology.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 01/2009; 34(6):1590-600. DOI:10.1038/npp.2008.216 · 7.05 Impact Factor
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