Potential metabolite markers of schizophrenia

Abstract

Schizophrenia is a severe mental disorder that affects 0.5–1% of the population worldwide. Current diagnostic methods are based on psychiatric interviews, which are subjective in nature. The lack of disease biomarkers to support objective laboratory tests has been a long-standing bottleneck in the clinical diagnosis and evaluation of schizophrenia. Here we report a global metabolic profiling study involving 112 schizophrenic patients and 110 healthy subjects, who were divided into a training set and a test set, designed to identify metabolite markers. A panel of serum markers consisting of glycerate, eicosenoic acid, β-hydroxybutyrate, pyruvate and cystine was identified as an effective diagnostic tool, achieving an area under the receiver operating characteristic curve (AUC) of 0.945 in the training samples (62 patients and 62 controls) and 0.895 in the test samples (50 patients and 48 controls). Furthermore, a composite panel by the addition of urine β-hydroxybutyrate to the serum panel achieved a more satisfactory accuracy, which reached an AUC of 1 in both the training set and the test set. Multiple fatty acids and ketone bodies were found significantly (P<0.01) elevated in both the serum and urine of patients, suggesting an upregulated fatty acid catabolism, presumably resulting from an insufficiency of glucose supply in the brains of schizophrenia patients.

Altered Coupling of Regional Cerebral Blood flow and Brain Temperature in Schizophrenia Compared with Bipolar Disorder and Healthy Subjects

“…7 Similarly, the patients with dementia of Alzheimer' type and with the alcohol abuse, who showed the decrement of brain glucose utilization and the increase in acetate uptake in the brain, [31][32][33] presented with a dysregulation between CMR and CBF. 34,35 The metabolic profiling study 36 and postmortem study 37 indicated the disordered energy metabolism in the brain of schizophrenia. Brain depends exclusively on glycolysis and oxidative phosphorylation to create ATP.…”

A Combined Metabonomic and Proteomic Approach Identifies Frontal Cortex Changes in a Chronic Phencyclidine Rat Model in Relation to Human Schizophrenia Brain Pathology

“…Providing a further link to mitochondrial dysfunction, we identified decreased levels of pyruvate kinase and we validated this finding at the functional level using pyruvate assay. Altered pyruvate levels were identified in a recent global metabolic profiling study involving 112 schizophrenic patients and 110 healthy subjects, and this was then used in a potential novel diagnostic panel for SCZ (Yang et al, 2013). In addition, converging evidence suggests that malfunction of energy supply through the brain glycolytic and TCA cycles is a causative factor of SCZ (Hazlett et al, 2004;Olsen et al, 2008).…”

Potential serum biomarkers from a metabolomics study of autism

“…22,23 A few metabolomic studies of autism have recently been carried out using different techniques in a variety of biospecimens. A urine study using a 1 H nuclear magnetic resonance (NMR) spectroscopy method has shown an elevated level of taurine and decreased glutamate in urine samples of patients with autism.…”