Copeptin as a predictor of relapse in patients with an acute psychotic episode: a prospective 1-year follow-up study

Abstract Arginine vasopressin (AVP), involved in higher brain functions, is increased in individuals with acute psychosis. Copeptin, a stable surrogate marker of AVP, predicts outcome in somatic diseases and increases under psychological stress. We hypothesized that in patients hospitalized with an acute psychosis, where a reliable predictor is currently lacking, copeptin could identify patients at higher risk for psychotic relapse. In this prospective, observational study, we enrolled 73 participants with an acute psychotic episode, either within a schizophrenia spectrum disorder (SSD) or an affective disorder (AD). At baseline, clinical characteristics and disease severity were assessed and fasting serum copeptin, cortisol, and sodium were measured. The primary endpoint was the potential of baseline copeptin to identify participants at greater risk for psychotic relapse using Cox proportional hazards models. The secondary endpoint was the differences between schizophrenia spectrum disorder and affective disorder. Patients with copeptin >6 pmol/L had a hazard of psychotic relapse 2.41 times higher (HR = 2.41, 95% CI [1.06, 5.52], p = 0.037) than patients with copeptin ≤6 pmol/L. Individuals with SSD and copeptin > 6pmol/L had a hazard of psychotic relapse 3.59 times higher (HR = 3.59, 95% CI [1.20, 10.76], p = 0.023) than those with copeptin ≤6 pmol/L. Copeptin remained an independent predictor of relapse after adjusting for serum sodium. Copeptin is a promising biomarker for identifying individuals at increased risk of psychotic relapse following hospitalization for acute psychosis, especially within the schizophrenia spectrum disorder subgroup. These results suggest that incorporating copeptin into clinical assessments could enhance personalized risk stratification and guide intensity of psychotic relapse prevention strategies.