| Summary: | 博士 === 國立中興大學 === 獸醫學系暨研究所 === 106 === Antipsychotic drugs are extensively employed to treat mental disorders, including bipolar disorder, delusional disorder, and schizophrenia. Second-generation antipsychotics (SGAs) carry a lower risk of extrapyramidal syndrome development than do first-generation antipsychotics. However, SGA use may result in weight gain, impaired glucose tolerance, hyperlipidemia, and increased adiposity, which in turn may lead to higher morbidity because of their association with hypertension, type II diabetes, stroke, and cardiovascular disease. The mechanisms underlying metabolic disturbance induced by SGAs, which have yet to be clarified, are probably multifactorial, involving the central and peripheral nervous systems. Erectile dysfunction (ED) may also occur as an adverse effect of these medicines. In this study, we examined the mechanisms underlying metabolic disturbance induced by SGAs, in this rodent model study, we also explored the association between ED and bipolar disorder in this large-scale population-based study. Our finding indicated that although some medication may increase the risk of ED in bipolar disorder patients, bipolar disorder patients without mood stabilizer, antipsychotics, or antidepressants treatment also had a higher risk of ED than the control group. Our In vivo study suggests that olanzapine treatment may increase food intake and body weight gain and trigger the accumulation of abdominal fat. In addition, olanzapine increased plasma triglyceride (TG), hepatic TG levels, plasma insulin, and hepatic SCD-1 protein levels. These results suggest a peripheral mechanism of olanzapine-induced dyslipidemia, involving enhanced lipogenesis through increased hepatic SCD-1 activity. Furthermore, our results evidenced that olanzapine may induce adverse metabolic effects during treatment, some of which may be related to the disturbance of lipid homeostasis in the liver. Owing to the association of these side effects with cardiovascular disease, clinicians should regularly monitor metabolic parameters in patients being treated with olanzapine. Additional study is required to understand and ameliorate the mechanisms underlying olanzapine-induced adverse metabolic effects.
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