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.

In a recent study, the association between metabolic risk genes and elevated fasting glucose level in patients with schizophrenia spectrum disorder. They have 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.

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. These 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.

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