Metabolic Profiling of Patients with Schizophrenia

M etabolomics (also referred to as metabonomics) is the comprehensive study of the metabolome, the repertoire of biochemicals (or small molecules) present in cells, tissue, and body fl uids. The study of metabolism at the global or "-omics " level is a new but rapidly growing fi eld that has the potential to have an impact upon medical practice [1–4]. At the center of metabolomics is the concept that an individual's metabolic state is a close representation of the individual's overall health status. This metabolic state refl ects what has been encoded by the genome and modifi ed by environmental factors. Today, clinicians capture only a very small part of the information contained in the metabolome, as revealed by a defi ned set of blood chemistry analyses to defi ne health and disease states. Examples include measuring glucose to monitor diabetes and measuring cholesterol for cardiovascular health. Such a narrow chemical analysis could potentially be replaced in the future with a metabolic signature that captures global biochemical changes in disease and upon treatment. Such metabolic signatures could provide: (1) prognostic, diagnostic, and surrogate markers for a disease state; (2) the ability to subclassify disease; (3) biomarkers for drug response phenotypes (pharmacometabolomics); and (4) information about mechanisms of disease. Indeed, sophisticated metabolomic analytical platforms and informatics tools have recently been developed that make it possible to defi ne initial metabolic signatures for several diseases [5–12]. A new study in PLoS Medicine by Elaine Holmes and colleagues is an early metabolomics experiment that attempts to identify biomarkers to assist in the diagnosis and treatment of schizophrenia [13]. The authors explore the use of a nuclear magnetic resonance–based metabolic profi ling platform (metabonomics) to defi ne biochemical changes in the cerebrospinal fl uid (CSF) and biomarkers in fi rst onset, drug-naïve patients with schizophrenia, and upon treatment with antipsychotic medications. Schizophrenia is a devastating mental illness that is poorly understood at the molecular level [14]. There are no validated biomarkers of schizophrenia that establish diagnosis or reliably predict response to treatment. While antipsychotic therapies were proven effective in short-term trials, most patients discontinue treatment over time for lack of effectiveness or development of side effects, and not all patients respond similarly to these medications [15]. An important clinical feature of schizophrenia is that patients have a greater risk than the general population for developing obesity and metabolic disorders such as type 2 diabetes …