ABNORMAL CARBOHYDRATE METABOLISM IN MOOD AND PSYCHOTIC DISORDERS

ABNORMAL

CARBOHYDRATE METABOLISM IN MOOD AND PSYCHOTIC DISORDERS: LINKING PATHWAY FLUX TO

William

Background:  Measurement of fluxes through metabolic pathways can provide data

that link genomic and proteonomic data to pathophysiology and eventually

pharmacotherapy.  A vulnerability to abnormal carbohydrate metabolism, evidenced

by increased rates of glucose intolerance or diabetes mellitus, has been

reported in patients with schizophrenia, bipolar disorder and major depression;

however, its relevance to the pathophysiology of these illnesses is unclear. 

This study investigated the polyol pathway—by which glucose is converted by

aldose reductase to sorbitol—in these illnesses, because it has been linked to

Methods: 

Using a gas chromatography-mass spectrometry (GC-MS) method, sorbitol, fructose,

and myoinositol concentrations were measured in 60 blocks of postmortem,

parietal lobe tissue—15 blocks from individuals with schizophrenia, bipolar

disorder, and nonpsychotic unipolar depression and 15 blocks from individuals

with no history of psychiatric illness or treatment—obtained from the Stanley

Results: 

Median sorbitol concentrations (nmol/g wet tissue) of the three psychiatric

brain groups were significantly (p<0.05) greater than normal controls: schizophrenia (116); bipolar disorder (88); nonpsychotic unipolar depression (114); normal controls (45), (χ²=13.6, df=3, p=0.004). These

differences persisted after adjusting for the effect of postmortem interval and

brain pH as well as after excluding three diabetic brains from the analysis. 

Furthermore, concentrations of fructose and sorbitol—the polyol pathway

metabolites of glucose—correlated positively and significantly with previously

reported elevated levels of fructose-1,6-bisphosphatase protein using a 2-D gel

technique with the same brains (Johnston-Wilson et al. Molecular Psychiatry

Conclusions:   These results suggest that increased glucose flux through the

brain polyol pathway occurs in some individuals with schizophrenia, bipolar

disorder, and unipolar major depression.  Correlation with proteonomic findings

related to carbohydrate metabolism suggests further that increased polyol

pathway activity may be part of a larger disturbance in brain carbohydrate

metabolism.  Further studies investigating the relationship of polyol pathway

activity to indices of brain disease are needed to determine whether increased

polyol pathway activity is involved in the pathophysiology of mood and psychotic