# Locomotor and endocrine alterations link to metabolic dysfunction induced by pathopharmacological interaction between neurodevelopmental disorders and antipsychotics: evidence from clinical and animal study

## TL;DR

This study shows that neurodevelopmental disorders and antipsychotics together increase metabolic risks, with altered movement and hormone levels playing a key role.

## Contribution

The novel contribution is identifying locomotor and endocrine changes as biological pathways linking neurodevelopmental disorders and antipsychotics to metabolic dysfunction.

## Key findings

- Metabolic imbalances were increased in adult female rats with Poly I:C exposure after long-term antipsychotic treatment.
- Altered locomotion and endocrine modulation, including changes in leptin, adiponectin, insulin, and prolactin, contribute to metabolic risk.
- There is a significant interaction effect between Poly I:C and antipsychotics on HOMA-IR, indicating combined metabolic impact.

## Abstract

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.

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.

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.

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.