Background Beyond the well-known metabolic side effects of second-generation antipsychotics (SGAs), recent studies suggest that neurodevelopmental disorders (NDDs) themselves confer an underlying susceptibility to metabolic dysregulation. However, it remains unclear whether a combined effect exists between SGAs and the NDD condition regarding metabolic syndrome, and which NDD-related pathophysiological changes contribute to metabolic disturbance. Methods This study applies a translational framework combining retrospective clinical data from drug-naïve children with NDDs and a prenatal polyinosinic:polycytidylic acid (Poly I:C) rat model. Results Baseline variations in lipid and glucose disturbances were observed in both cohorts, and these metabolic imbalances were further increased in adult female rats following long-term olanzapine or risperidone treatment, with significant interaction effect between Poly I:C and SGA observed for HOMA-IR. Moreover, the significant effects of both Poly I:C and SGAs on adipokines (leptin and adiponectin) and locomotor activity, with SGA-driven changes in insulin and prolactin, indicate that altered locomotion and divergent endocrine modulation serve as candidate pathways contributing to NDD-related metabolic risk. Discussion These results highlight that NDD-related locomotor and endocrine changes should be considered as potential biological factors when finding effective strategies for preventing metabolic events during SGAs medication. These results underscore the clinical importance of metabolic monitoring in pediatric psychopharmacology, even prior to pharmacologic exposure.
Zeng et al. (Tue,) studied this question.