Assessment of Appetite-Regulating Hormones Provides Further Evidence of Altered Adipoinsular Axis in Early Psychosis

It has been found that antipsychotic-naive patients with first-episode psychosis (FEP) present with impaired hormonal regulation of appetite in terms of low leptin and high insulin levels (the adipoinsular axis). These findings imply that certain intrinsic mechanisms might play a role in the development of metabolic dysregulation in early psychosis. However, clinical correlates of this phenomenon remain unknown. Moreover, these alterations have not been tested in individuals at familial high risk of psychosis (FHR-P). In this study we aimed to assess the levels of adiponectin, insulin, leptin, glucose, total cholesterol, lipoproteins and triglycerides in FEP patients, unaffected offspring of schizophrenia patients (FHR-P individuals) and healthy controls (HCs) with respect to cognitive performance and psychopathological manifestation. Participants were 35 FEP patients, 33 FHR-P individuals, and 32 HCs. Cognitive performance was assessed using the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). The levels of leptin and high-density lipoproteins (HDL) were significantly lower (leptin: 10.7 +/- 15.7 vs. 12.6 +/- 10.1, p = 0.046, and HDL: 48.0 +/- 16.9 vs. 59.8 +/- 17.5 mg/dl, p = 0.007), while the levels of triglycerides and insulin were significantly higher (triglycerides: 137.4 +/- 58.8 vs. 77.5 +/- 33.2 mg/dl, p < 0.001, and insulin: 15.2 +/- 13.1 vs. 9.6 +/- 5.0 mu IU/ml, p = 0.023) in FEP patients compared to HCs. These differences were significant after controlling for the effects of potential confounding factors. No significant differences in the levels of serum markers between FHR-P individuals and HCs were found. There was a significant negative correlation between the level of leptin and the RBANS language score after covarying for potential confounding factors in FEP patients (B = -0.226, p = 0.006) but not in other subgroups of participants. Our findings confirm impairment of adipoinsular axis in early psychosis. However, results of our study do not support the hypothesis that familial liability to psychosis might be associated with metabolic dysregulation. Leptin levels might be associated with cognitive deficits in FEP patients. Longitudinal studies of individuals at risk of psychosis are needed to provide insights into causal mechanisms underlying our results.