Relationship of cerebrospinal fluid glucose metabolites to MRI deep white matter hyperintensities and treatment resistance in bipolar disorder patients.
OBJECTIVE
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 (rho = 0.487, p = 0.029) and fructose (rho = 0.474, p = 0.035). An index of treatment resistance correlated significantly with deep WMH volume (rho = 0.578, p = 0.008), sorbitol (rho = 0.542, p = 0.013), and fructose (rho = 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.
Regenold
William T
WT
Department of Psychiatry, Division of Geriatric Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.wregenol@psych.umaryland.edu
Hisley
K Calvin
KC
Phatak
Pornima
P
Marano
Christopher M
CM
Obuchowski
Abraham
A
Lefkowitz
David M
DM
Sassan
Amritpal
A
Ohri
Sameer
S
Phillips
Tony L
TL
Dosanjh
Narveen
N
Conley
Robert R
RR
Gullapalli
Rao
R
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000097:blood / Q000134:cerebrospinal fluid* / Q000473:pathology*; D005260:Female; D005632:Fructose / Q000097:blood / Q000134:cerebrospinal fluid; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D005947:Glucose / Q000134:cerebrospinal fluid*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D012559:Schizophrenia / Q000134:cerebrospinal fluid / Q000473:pathology; D013012:Sorbitol / Q000097:blood / Q000134:cerebrospinal fluid; D013223:Statistics as Topic; D055815:Young Adult
D005632:Fructose; D013012:Sorbitol; D005947:Glucose