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Metabolic syndrome (MetS) is a significant risk factor for cardiovascular disease and diabetes. MetS is more prevalent in people with schizophrenia compared to the general population. Risk factors for developing MetS include poor nutrition, sedentary behavior, cigarette smoking, and treatment with antipsychotic medications.1 This article reviews MetS in people with schizophrenia, focusing on causes of MetS, appropriate monitoring, prevention, and treatment.
Definition of Metabolic Syndrome
MetS is a group of clinical findings that increase a person's risk for cardiovascular disease and type 2 diabetes. Criteria for MetS include central obesity, elevated blood pressure, elevated triglycerides, hyperglycemia, and low high-density lipoprotein. There is slight variation between the expert consensus guidelines criteria for MetS, with the International Diabetes Federation (IDF) including abdominal obesity as necessary criteria. However, a subsequent unifying criteria has been proposed by the IDF and the American Heart Association/National Heart, Lung, and Blood Institute2 (Table 1). Under this definition, the presence of 3 of the 5 risk factors is consistent with a definition of MetS.
Morbidity and Mortality
People with schizophrenia have a 10- to 25-year reduction in life expectancy compared to the general population.3 Physical diseases, including cardiovascular disease, account for most of the increased mortality rate.4 MetS, which imparts increased risk for cardiovascular disease, is prevalent among people with schizophrenia, and it is estimated that the prevalence of MetS in people with schizophrenia is approximately 33%, and the relative risk is 1.87 times higher than in the general population.5 Further, people with schizophrenia often have limited access to medical care, contributing to elevated morbidity and mortality rates.6
Risk Factors and Mechanisms
Weight gain, specifically abdominal obesity, is one of the earliest risk factors for developing MetS. Among people with schizophrenia, treatment with antipsychotic medications can cause significant weight gain. Potential mechanisms for antipsychotic medication-induced weight gain include dysregulation of the hypothalamic-targeting hormones leptin and ghrelin, 5-hydroxytryptamine receptor 2c receptor antagonism affecting satiety signaling, and histamine H1 receptor antagonism increasing energy intake and inappetite.7,8 Both first-generation and second-generation antipsychotic medications have been associated with weight gain, although mean weight gain varies substantially between antipsychotic drugs. A recent network meta-analysis of 32 antipsychotic medications showed not only olanzapine and clozapine, but also quetiapine, risperidone, iloperidone, and risperidone caused significant weight gain when...