Investigation of the Role of Gut Microbiota in Antipsychotic-Induced Metabolic Dysfunction in Patient with Schizophrenia

Patients suffer from mental disorders have 2~3 times higher mortality than healthy individuals. Other than suicide and accidental deaths, metabolic syndrome and cardiovascular disease are the major causes of deaths due to antipsychotic treatment. Patients with schizophrenia often suffer from metabolic dysfunction due to the long-term use of atypical antipsychotics. As much as 50% of patients receiving Olanzapine or Clozapine experience metabolic-related side effects, contributing to poor quality of life, adverse health outcomes, and poor adherence to treatment, and ultimately imposes a considerable burden on the health care system. Gut microbiota is an important modulator of brain development and function. Recent studies showed gut microbiota can regulate the concentrations of neurotransmitters such as serotonin and γ-aminobutyric acid (GABA) to influence the host immune and nervous systems. The bidirectional signaling between the gut microbiota, gastrointestinal tract and the brain has been dubbed the microbiota–gut–brain axis. The role of gut microbiota in psychology, neurosciences and behavior is an emerging field of research under extensive studies. The aims of this study are to (1) investigate the relationships between gut microbiota, antipsychotic drug-induced metabolic dysfunction, immune response and behavior changes; and (2) investigate the effect of probiotic on gut ecology and the prevention or improvement of metabolic disorders to reduce side-effects brought about by the antipsychotic drug treatment. The experiment will be conducted using a rat model, and also human subjects with schizophrenic disorder will be enrolled into the study as well. The goals of the study are to minimize the side effects using biotherapies to improve adherence to treatment and to prevent or delay the onset of metabolic dysfunction and cardiovascular disease in schizophrenic patients. The findings from this study will open a new range of treatment possibilities as well as reduce the mortality of patients with schizophrenia.