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
