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

Department of Psychiatry, University of California, San Francisco, San Francisco, California, United States
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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    • "The most frequent abnormal morphological findings are lateral ventricular enlargements and increased rates of deep white matter hyperintensities (Kempton et al, 2008; Beyer et al, 2009). The association between white matter pathology and BD has been further supported by morphometric studies showing reductions in total white matter volumes (Strakowski et al, 1993; Kieseppa et al, 2003; Davis et al, 2004; Rosso et al, 2007). Patients with cerebral small vessel disease share common features with bipolar patients such as poor performance on tests of executive function and processing speed, generalized brain atrophy as well as ventricular enlargement, blood brain barrier (BBB) dysfunction , and white matter changes in periventricular as well as in the deep white matter (Chui, 2007). "
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    ABSTRACT: Bipolar disorder (BD) is characterized by mood swings between manic and depressive states. The etiology and pathogenesis of BD is unclear, but many of the affected cognitive domains, as well as neuroanatomical abnormalities, resemble symptoms and signs of small vessel disease. In small vessel disease, cerebrospinal fluid (CSF) markers reflecting damages in different cell types and subcellular structures of the brain have been established. Hence, we hypothesized that CSF markers related to small vessel disease may also be applicable as biomarkers for bipolar disorder. To investigate this hypothesis, we sampled CSF from 133 patients with bipolar disorder and 86 healthy controls. The concentrations of neurofilament light chain (NF-L), myelin basic protein (MBP), S100B, and heart-fatty acid binding protein (H-FABP) were measured in CSF and analyzed in relation to diagnosis, clinical characteristics, and ongoing medications. Hereby we found an elevation of the marker of subcortical axonal damage, NF-L, in bipolar subjects. We also identified positive associations between NF-L and treatment with atypical antipsychotics, MBP and lamotrigine, and H-FABP and lithium. These findings indicate axonal damage as an underlying neuropathological component of bipolar disorder, though the clinical value of elevated NF-L remains to be validated in follow-up studies. The associations between current medications and CSF brain injury markers might aid in the understanding of both therapeutic and adverse effects of these drugs.Neuropsychopharmacology accepted article peview online, 03 April 2014; doi:10.1038/npp.2014.81.
    Preview · Article · Apr 2014 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
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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.
    Full-text · Article · Nov 2011 · Progress in Neuro-Psychopharmacology and Biological Psychiatry
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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.
    Full-text · Article · Mar 2011 · Cerebral Cortex
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