Higher schizotypy predicts better metabolic profile in unaffected siblings of patients with schizophrenia

摘要

Abstract Rationale Type 2 diabetes (T2D) is more frequent in schizophrenia (Sz) than in the general population. This association is partly accounted for by shared susceptibility genetic variants. Objective We tested the hypotheses that a genetic predisposition to Sz would be associated with higher likelihood of insulin resistance (IR), and that IR would be predicted by subthreshold psychosis phenotypes. Methods Unaffected siblings of Sz patients ( n ?=?101) were compared with a nonclinical sample ( n ?=?305) in terms of IR, schizotypy (SzTy), and a behavioural experiment of “jumping to conclusions”. The measures, respectively, were the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Structured Interview for Schizotypy-Revised (SIS-R), and the Beads Task (BT). The likelihood of IR was examined in multiple regression models that included sociodemographic, metabolic, and cognitive parameters alongside group status, SIS-R scores, and BT performance. Results Insulin resistance was less frequent in siblings (31.7%) compared to controls (43.3%) ( p ? p ? p ?=?0.015]. Conclusion Higher dopaminergic activity may contribute to both schizotypal features and a favourable metabolic profile in the same individual. This is compatible with dopamine’s regulatory role in glucose metabolism via indirect central actions and a direct action on pancreatic insulin secretion. The relationship between dopaminergic activity and metabolic profile in Sz must be examined in longitudinal studies with younger unaffected siblings.