Assessment of Insulin Resistance Among Drug-Naive Patients With First-Episode Schizophrenia in the Context of Hormonal Stress Axis Activation

Abstract

Before the introduction of antipsychotics, links between schizophrenia and abnormal glucose metabolism levels were found in the late 1800s as an increased prevalence of diabetes in families with a history of “insanity.”1 Furthermore, it is known that some patients with psychosis require higher dosages than other patients when applying insulin therapy, suggestive of insulin resistance.2 A recent meta-analysis by Pillinger et al1 assessed insulin resistance and found an elevated homeostatic model assessment of insulin resistance (HOMA-IR) among drug-naive patients with first-episode schizophrenia (n = 560) compared with controls (n = 450).1 They highlighted hormonal stress axis activation and lifestyle factors as potential confounders.1 Stress hormones, such as cortisol and catecholamines, are catabolic and functional antagonists of insulin. Antipsychotic-naive individuals with first-episode psychosis exhibit higher baseline cortisol levels and a blunted cortisol awakening response compared with controls.1,3 To test whether insulin resistance in schizophrenia can be discerned from stress-related and medication effects, we assessed HOMA-IR and stress hormone levels among drug-naive patients with first-episode schizophrenia and matched controls.