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

Abstract

Background Magnetic resonance imaging (MRI) white matter hyperintensities (WMHs) are found at higher rates in patients with affective disorders, particularly late-life or treatment-resistant disorders. Studies support a vascular pathogenesis for WMHs in late-life onset disorders; however, pathogenesis in typical early-life onset disorders is less clear. Based on associations between diabetes mellitus and both WMHs and affective disorders, this study investigated the relationship between WMHs and brain glucose metabolism by the polyol pathway—a pathway linked to nervous tissue disease in diabetes. Methods Burdens of fluid-attenuated inversion recovery (FLAIR) WMHs were quantified and correlated with cerebrospinal fluid (CSF) concentrations of glucose metabolites in 10 nondiabetic inpatients with treatment-resistant bipolar, unipolar, and schizoaffective disorders and 10 nondiabetic control patients who had been investigated clinically for transient neurological symptoms. Results Deep but not periventricular WMH burden correlated positively and significantly with elevated CSF concentrations of sorbitol, the specific polyol pathway metabolite of glucose ( ρ=0.86, p=0.002), in the affective disorders but not the control group. Limitations This was a pilot study with a relatively small number of subjects; therefore, conclusions are tentative. Controls were not healthy subjects; they were patients with transient neurological symptoms. Conclusions This is the first reported evidence of a relationship between WMHs and increased brain glucose metabolism by the polyol pathway in patients with affective disorders. More extensive studies are necessary to determine whether this preliminary finding represents a pathogenetic relationship.