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 Research & Giving News Article  and Lipid Metabolism Study reveals beneficial metabolic impact of three antipsychotic drugs Although antipsychotic drugs are known for the actions they produce in the brain, the study reveals that some of the hundreds of chemicals, or metabolites, that they leave behind in the bloodstream may help reverse abnormal levels of certain lipids in people with schizophrenia. The study results appear in a paper published in the May 2007 issue of Molecular Psychiatry. Its lead author is Rima Kaddurah-Daouk, Ph.D., a NARSAD 2005 Independent Investigator and associate professor of biological psychiatry at Duke University Medical Center. She and colleagues employed a method called metabolomics -- the measurement of thousands of metabolites, or chemical byproducts of the body's cellular processes -- to analyze the blood of schizophrenia patients and to correlate results with their responses to therapy. . Although it is widely held that schizophrenia is caused by an imbalance in neurotransmitter molecules that help send messages between nerve cells in the brain, some scientists recently have begun to investigate whether lipids, small fatty molecules such as cholesterol and triglycerides, also may play a role in the disease and in patients’ response to therapy. Dr. Kaddurah-Daouk and colleagues measured 300 different lipids in blood drawn from 50 patients with schizophrenia before and after treatment with the atypical antipsychotic drugs olanzapine (Zyprexa), risperidone (Risperdal), and aripiprazole (Abilify). Prior to treatment, patients were found to have lower levels of the beneficial lipids used to make membranes involved in storing and communicating information in the brain. These lipid changes were partially reversed in patients treated with antipsychotic medications, said Joseph McEvoy, M.D., associate professor of biological psychiatry at Duke and study co-investigator. "This technique allows us to identify the specific metabolic changes that are caused by the most commonly used drugs for schizophrenia," Dr. McEvoy said. "The study is extremely important because it is giving us more information about how these drugs work," added Ranga Krishnan, M.D., chairman of psychiatry at Duke and senior study investigator. "Now we can begin to develop better medicines that target the specific metabolites important for the disease but not those that could lead to detrimental side effects." In living organisms, lipids are used for energy storage, serve as the structural components of cell membranes, and constitute important signaling molecules. Although the term lipid is often used as a synonym for fat, the latter is in fact a subgroup of lipids called triglycerides. Scientists are still trying to sort out which of the lipids that are specifically modified in schizophrenia are beneficial and which ones result in metabolic side effects. "Clearly we need to put forth a major effort to link the changes in the blood to what happens in the brain," Dr. Kaddurah-Daouk said. She thinks metabolomics could help explain what makes some people more susceptible to schizophrenia, and why some people respond better to treatment than others or develop metabolic side effects. Future experiments focused on correlating lipid signatures with the clinical outcomes of schizophrenia patients might yield an important tool for determining the best treatment for each patient, she added. In addition to NARSAD, the study was funded by the Stanley Medical Research Institute. This story is adapted in part with permission of Duke University. |
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