Metabolic Signatures and Biomarkers in Schizophrenia

Metabolic Signatures and Biomarkers in First Episode and Recurrent Patients With Schizophrenia in Comparison to Healthy Controls

We plan to use a metabolomics lipid platform to map biochemical signatures in unmedicated schizophrenic patients prior to and 4 weeks post treatment with the antipsychotic drug aripiprazole and compare that to lipid perturbations induced by risperidone. These drugs have inherently different risk for metabolic adverse effects and patients respond to them differently. Metabolic signatures for the drugs capture significant biochemical information that could explain part of the basis for varied drug response within individuals and will highlight pathways implicated in drug action and in disease pathogenesis possibly enabling new drug design strategies. In addition, we will compare patients to healthy controls at baseline in regard lipid profiles.

Schizophrenia (SCH) is a devastating mental disease that affects the human population worldwide with an incidence of about 1%. Most individuals with this illness benefit from long-term pharmacotherapy, however, the therapeutic effects of antipsychotic treatment are inconsistent, incomplete, and often countered by significant side-effects associated with long-term physical morbidity (e.g., tardive dyskinesia, obesity, hyperglycemia, hyperlipidemia. Metabolomics is a powerful new technology that provides a snap shot of biochemical pathways at a particular point in time. It has been earmarked as an important area to develop under the NIH roadmap initiative. We plan to use this platform to map biochemical signatures in unmedicated schizophrenic patients prior to and 4 weeks post treatment with the antipsychotic drug aripiprazole and compare that to lipid perturbations induced by risperidone. These drugs have inherently different risk for metabolic adverse effects and patients respond to them differently. Metabolic signatures for the drugs capture significant biochemical information that could explain part of the basis for varied drug response within individuals and will highlight pathways implicated in drug action and in disease pathogenesis possibly enabling new drug design strategies.In addition, we will compare patients to healthy controls at baseline in regard lipid profiles, to assess whether lipid profiles differ between unmedicated schizophrenia patients and healthy controls.

Blood is drawn for baseline. 20 Subjects are randomly assigned to receive Aripiprazole for weeks weeks with a starting dose of 10mg/day and the dose will be titrated to a maximum of 30mg /day based on effectiveness and tolerability. After 4 weeks of treatment, blood will be drawn again for metabolomics.

Blood will be drawn for baseline evaluation. 20 Subjects will be randomly assigned to receive risperidone at a starting dose of 2mg/day, and can be increased to 6mg/day based on response of the subject. After 4 weeks of medication, blood is drawn again.

Fasting blood samples will be drawn from healthy volunteers to match age, race and gender with the research subjects for comparison.

Plasmalogens are a subclass of glycerophospholipids and ubiquitous constituents of cellular membranes and serum lipoproteins. Several neurological disorders show decreased level of plasmalogens.

Inclusion Criteria: Age 18-60 years Diagnosis of schizophrenia Actively psychotic No more than a single dose of antipsychotic in the preceding 2 weeks Exclusion Criteria: Mental retardation, epilepsy or history of head trauma Substance use disorder that explains the majority of the psychopathology Pregnant or lactating females

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