Abstract
Background: Metabolic risk factors represent a major cause of increased coronary heart disease morbidity and mortality among psychosis patients. Although antipsychotic medication may lead to hyperglycemia, an association to severe mental illness was established before the introduction of antipsychotics. Methods: We investigated the association between metabolic risk genes and elevated fasting glucose level in patients with schizophrenia spectrum disorder. We applied two association models; (i) case-case where psychosis patients with elevated fasting glucose level (≥5.6 mmol/l) or diagnosed diabetes (n=263) were compared to patients with normal glucose level (n=389), and (ii) case-control model where psychosis patients with elevated fasting glucose level were compared to population-derived controls (n=494). Association analyses were adjusted for age, sex, smoking, family history of diabetes, and waist circumference. (iii) We also investigated whether metabolic genes were associated with schizophrenia spectrum disorder independent of fasting glucose. Results: No differences between schizophrenia spectrum diagnoses regarding genetic associations with increased fasting glucose were detected. In a case-case model, a genetic variant in IGF2BP2 was associated with elevated fasting glucose level among persons with schizophrenia spectrum disorder. In a case-control model associations were found with genetic variants in the NOTCH2, THADA, WFS1, P2RX7, and MNTR1B. A genetic variant in PPARD was nominally associated with schizophrenia spectrum disorder independent of glucose level. Conclusion: Our findings indicate that common metabolic polymorphisms associated with elevated fasting glucose among schizophrenia spectrum disorder patients may at least partially be explained by increased vulnerability in schizophrenia spectrum disorders for genes associate with elevated fasting glucose in the population.
Highlights
Schizophrenia is a severe psychiatric disorder characterized by ubiquitous psychotic features and symptoms such as disorganized thinking and behavior, representing social dysfunction
Severe mental illness including schizophrenia has been shown to be associated with a significant excess of somatic illnesses including increased risk for hyperglycemia and diabetes type 2, evident long before the introduction of antipsychotic drugs, which have further increased the diabetes risk, resulting in a more than doubled risk of dying from cardiovascular causes of death compared with the general population [4]
In a previous clinical study of metabolic risk in persons with schizophrenia or other psychosis compared with the population, we reported that psychosis per se was an important and independent risk factor for increased fasting glucose, controlling for differences in waist circumference, gender, age, blood pressure, tobacco use and family history of diabetes [6]
Summary
Schizophrenia is a severe psychiatric disorder characterized by ubiquitous psychotic features and symptoms such as disorganized thinking and behavior, representing social dysfunction. Severe mental illness including schizophrenia has been shown to be associated with a significant excess of somatic illnesses including increased risk for hyperglycemia and diabetes type 2, evident long before the introduction of antipsychotic drugs, which have further increased the diabetes risk, resulting in a more than doubled risk of dying from cardiovascular causes of death compared with the general population [4]. Suicide rates are highly elevated in this group of patients, increased cardiovascular causes of death, not suicide, is the major contributor to excess mortality [4,5]. Metabolic risk factors represent a major cause of increased coronary heart disease morbidity and mortality among psychosis patients. Antipsychotic medication may lead to hyperglycemia, an association to severe mental illness was established before the introduction of antipsychotics
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