Association of Insulin Resistance With Schizophrenia Polygenic Risk Score and Response to Antipsychotic Treatment

Patients with schizophrenia show an increased risk of impaired glucose metabolism, 1 yet the mechanism behind this association remains unknown. Multiple studies have attempted to identify the determinants of insulin resistance (IR) in schizophrenia, with evidence suggesting that it cannot be fully explained by disease duration, symptom severity, medication effects, obesity, or hormonal stress axis activation, and other interacting factors are likely involved. 1 While family and genome-wide association studies have suggested a shared genetic vulnerability between schizophrenia and abnormal glucose metabolism, 2 to our knowledge, a direct link between schizophrenia genetic risk and insulin resistance has not been investigated. Here, we examine the association between IR, schizophrenia polygenic risk, and treatment outcomes in first-episode, antipsychotic-naive patients with schizophrenia and matched healthy individuals while controlling for demographic, lifestyle, and clinical factors.