Relationship of white matter hyperintensities to cerebrospinal fluid glucose polyol pathway metabolites—a pilot study in treatment-resistant affective disorder patients

Regenold, William T.; Hisley, K. Calvin; Obuchowski, Abraham; Lefkowitz, David M.; Marano, Christopher; Hauser, Péter

doi:10.1016/j.jad.2004.10.010

Cited by 20 publications

(15 citation statements)

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“…Highly heterogeneous, these studies reported decreased fractional anisotropy values in the frontal, prefrontal and, to a lesser extent, parietal, temporal and occipital lobes, 16,[18][19][20][21] decreased or increased fractional anisotropy values in several white matter tracts and projection fibres of the internal capsule and thalamic radiations, 23,24,[50][51][52] and decreased fractional anisotropy in association fibres that connect the frontal and prefrontal cortex with various lobes of the cerebral hemisphere.…”

Section: White Matter Changes In Patients With Bipolar Disordermentioning

confidence: 99%

“…Overall, the few previous DTI studies reported reduced fractional anisotropy and increased radial diffusion in the frontal and prefrontal lobes, internal capsule, corpus callosum and uncinate fasciculus of patients with bipolar disorder. [18][19][20][21][22][23][24] Tract-based spatial statistics (TBSS) is a recently introduced advanced analysis technique that projects all individual DTI parameters onto a group average white matter skeleton, reducing potential spatial misregistrations. 25 Only 2 TBSS studies were performed in young patients with bipolar disorder, showing a reduction in fractional anisotropy, notably in the corpus callosum and fornix 22 as well as in the right uncinate fasciculus.…”

Section: Introductionmentioning

confidence: 99%

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Combined analysis of grey matter voxel-based morphometry and white matter tract-based spatial statistics in late-life bipolar disorder

Haller

Xekardaki

Delaloye

et al. 2011

jpn

109

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Previous magnetic resonance imaging (MRI) studies in young patients with bipolar disorder indicated the presence of grey matter concentration changes as well as microstructural alterations in white matter in various neocortical areas and the corpus callosum. Whether these structural changes are also present in elderly patients with bipolar disorder with long-lasting clinical evolution remains unclear

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Section: White Matter Changes In Patients With Bipolar Disordermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Combined analysis of grey matter voxel-based morphometry and white matter tract-based spatial statistics in late-life bipolar disorder

Haller

Xekardaki

Delaloye

et al. 2011

jpn

109

View full text Add to dashboard Cite

show abstract

“…The breakdown, or loss of myelin (demyelination), such as seen in several neurodegenerative diseases (e.g., multiple sclerosis), results in impaired nerve impulse transmission. Higher rates of white matter hyperintensities (WMHs) in patients with mood disorders, particularly late-life or treatment-resistant disorders, also implicate white matter abnormalities in mood disorder etiology (130).…”

Section: Magnet Based Neuroimaging Of Brain Function: Diffusion Tensomentioning

confidence: 99%

Neuroimaging Approaches in Mood Disorders: Technique and Clinical Implications

Konarski¹,

McIntyre²,

Soczynska³

et al. 2007

Annals of Clinical Psychiatry

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Advances in neuroimaging technology have refined models of disease pathophysiology in mood disorders and the mechanistic basis of antidepressant action. Multivariate analysis of functional and structural neuroimaging data, longitudinal analysis in the depressed and remitted states, and inclusion of representative patients with medical and psychiatric comorbidities will enhance the clinical translation of future research findings.

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“…We hypothesized that abnormal brain glucose metabolism, specifically increased conversion of glucose to sorbitol through the polyol pathway, contributes to white matter lesions, manifested by WMHs that underlie treatment resistance. We have also previously reported elevated cerebrospinal fluid (CSF) sorbitol concentration in nondiabetic patients with bipolar and unipolar disorders (27) and a positive correlation between elevated CSF sorbitol and deep WMHs in patients with treatment‐resistant affective disorders (28).…”

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confidence: 86%

Relationship of cerebrospinal fluid glucose metabolites to MRI deep white matter hyperintensities and treatment resistance in bipolar disorder patients

Regenold¹,

Hisley²,

Phatak³

et al. 2008

Bipolar Disorders

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Objectives Both diabetes mellitus and magnetic resonance image (MRI) deep white matter hyperintensities (WMHs) are more common in bipolar disorder (BD) patients than in matched controls. Deep—as opposed to periventricular—WMHs and diabetes are associated with treatment resistance and poorer outcome. This study investigated whether brain glucose metabolism by the polyol pathway—a pathway linked to nervous tissue disease in diabetes—is related to deep WMH volume and treatment resistance in BD patients. Methods Volumes of fluid-attenuated inversion recovery WMHs were quantified and correlated with cerebrospinal fluid (CSF) concentrations of glucose metabolites in 20 nondiabetic patients with BD and nondiabetic comparison subjects with schizophrenia (n = 15) or transient neurologic symptoms (neurologic controls, n = 15). Results BD patients, but not schizophrenic patients, had significantly greater volumes of deep but not periventricular WMHs compared to neurologic controls. BD subjects also had significantly greater CSF concentrations of sorbitol and fructose (the polyol pathway metabolites of glucose) compared to controls. Significant positive correlations between CSF metabolites and WMH volumes were found only in the BD group and were between deep WMH volumes and CSF sorbitol (ρ = 0.487, p = 0.029) and fructose (ρ = 0.474, p = 0.035). An index of treatment resistance correlated significantly with deep WMH volume (ρ = 0.578, p = 0.008), sorbitol (ρ = 0.542, p = 0.013), and fructose (ρ = 0.692, p = 0.001) in BD subjects but not in other subjects. Conclusions This is the first reported evidence of relationships between abnormal brain glucose metabolism and both deep WMHs and treatment resistance in a group of BD patients. Further studies are necessary to determine the significance of these findings to BD pathophysiology.

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Relationship of white matter hyperintensities to cerebrospinal fluid glucose polyol pathway metabolites—a pilot study in treatment-resistant affective disorder patients

Cited by 20 publications

References 50 publications

Combined analysis of grey matter voxel-based morphometry and white matter tract-based spatial statistics in late-life bipolar disorder

Combined analysis of grey matter voxel-based morphometry and white matter tract-based spatial statistics in late-life bipolar disorder

Neuroimaging Approaches in Mood Disorders: Technique and Clinical Implications

Relationship of cerebrospinal fluid glucose metabolites to MRI deep white matter hyperintensities and treatment resistance in bipolar disorder patients

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