title: Relationship of cerebrospinal fluid glucose metabolites to MRI deep white matter hyperintensities and treatment resistance in bipolar disorder patients.
abstract: 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.
authors.affiliation: Department of Psychiatry, Division of Geriatric Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.wregenol@psych.umaryland.edu
authors.forename: William T
authors.initials: WT
authors.lastname: Regenold
authors.forename: K Calvin
authors.initials: KC
authors.lastname: Hisley
authors.forename: Pornima
authors.initials: P
authors.lastname: Phatak
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Marano
authors.forename: Abraham
authors.initials: A
authors.lastname: Obuchowski
authors.forename: David M
authors.initials: DM
authors.lastname: Lefkowitz
authors.forename: Amritpal
authors.initials: A
authors.lastname: Sassan
authors.forename: Sameer
authors.initials: S
authors.lastname: Ohri
authors.forename: Tony L
authors.initials: TL
authors.lastname: Phillips
authors.forename: Narveen
authors.initials: N
authors.lastname: Dosanjh
authors.forename: Robert R
authors.initials: RR
authors.lastname: Conley
authors.forename: Rao
authors.initials: R
authors.lastname: Gullapalli
mesh_terms: 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
chemical_list: D005632:Fructose; D013012:Sorbitol; D005947:Glucose