ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Psychopharmacology
Locomotor and endocrine alterations link to metabolic dysfunction induced by pathopharmacological interaction between neurodevelopmental disorders and antipsychotics: Evidence from clinical and animal study
Menglu Zeng 1
Xinyu Yang 2
Zhenju Cao 1
Huiyu Chen 1
Yanfang Lu 1
Chen Xu 1
Danlin Weng 1
Anying Shen 2
Fei Xue 1
Wei Lin 2,3
Jianan Shi 1
Shuangyan Yang 1
Aifang Zhang 1
Fuchun Zhong 1
Yueqing Su 1
1. Fujian Maternity and Child Health Hospital, Fuzhou, China
2. Fujian Medical University, Fuzhou, China
3. Affiliated Fuzhou First Hospital of Fujian Medical University, Fuzhou, China
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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.
Summary
Keywords
Adiponectin, Insulin, Leptin, locomotor activity, Metabolic disturbance, Neurodevelopmental disorders, Poly I:C, second-generation antipsychotic
Received
10 December 2025
Accepted
18 February 2026
Copyright
© 2026 Zeng, Yang, Cao, Chen, Lu, Xu, Weng, Shen, Xue, Lin, Shi, Yang, Zhang, Zhong and Su. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Fuchun Zhong; Yueqing Su
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