RT Journal Article SR Electronic T1 Long-Term Effects of Early Adolescent Second-Generation Antipsychotic Exposure on Body Weight, Caloric Intake, and Metabolism-Associated Gene Expression JF bioRxiv FD Cold Spring Harbor Laboratory SP 2024.09.29.615669 DO 10.1101/2024.09.29.615669 A1 Soto, Paul L. A1 Young, Michael E. A1 Nguyen, Serena A1 Federoff, Megan A1 Goodson, Mia A1 Morrison, Christopher D. A1 Batdorf, Heidi M. A1 Burke, Susan J. A1 Collier, J. Jason YR 2024 UL http://biorxiv.org/content/early/2024/10/01/2024.09.29.615669.abstract AB The use of second-generation antipsychotic (SGA) medications in pediatric patients raises concerns about potential long-term adverse outcomes. The current study evaluated the long-term effects of treatment with risperidone or olanzapine on body weight, caloric intake, serum insulin, blood glucose, and metabolism-associated gene expression in C57Bl/6J female mice. Compared to mice treated with vehicle, female mice treated with risperidone or olanzapine gained weight at higher rates during treatment and maintained higher body weights for months following treatment cessation. During high-fat diet feeding, some groups of treated mice gained weight at higher rates than their respective control groups, but the finding was not consistent across experiments. Finally, female mice previously treated with olanzapine also exhibited increased expression of genes associated with inflammation and lipogenesis. These findings suggest that pediatric use of SGA medications that induce excess weight gain during treatment may exert persistent effects on body weight and gene expression and such outcomes may form an important aspect of assessing risk-to-benefit ratios in prescribing decisions.Competing Interest StatementThe authors have declared no competing interest.