Telencephalon Organoids Derived from an Individual with ADHD Show Altered Neurodevelopment of Early Cortical Layer Structure

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that occurs in early childhood and can persist to adulthood. It can affect many aspects of a patient's daily life, so it is necessary to explore the mechanism and pathological alterations. For this purpose, we applied induced pluripotent stem cell (iPSC)-derived telencephalon organoids to recapitulate the alterations occurring in the early cerebral cortex of ADHD patients. We found that telencephalon organoids of ADHD showed less growth of layer structures than control-derived organoids. On day 35 of differentiation, the thinner cortex layer structures of ADHD-derived organoids contained more neurons than those of control-derived organoids. Furthermore, ADHD-derived organoids showed a decrease in cell proliferation during development from day 35 to 56. On day 56 of differentiation, there was a significant difference in the proportion of symmetric and asymmetric cell division between the ADHD and control groups. In addition, we observed increased cell apoptosis in ADHD during early development. These results show alterations in the characteristics of neural stem cells and the formation of layer structures, which might indicate key roles in the pathogenesis of ADHD. Our organoids exhibit the cortical developmental alterations observed in neuroimaging studies, providing an experimental foundation for understanding the pathological mechanisms of ADHD.

Automated summary

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects individuals from childhood to adulthood. In this study, induced pluripotent stem cell (iPSC)-derived telencephalon organoids were used to recreate the alterations observed in the early cerebral cortex of ADHD patients. The ADHD-derived organoids exhibited slower growth of layer structures, increased neuron density, decreased cell proliferation, altered cell division patterns, and increased cell apoptosis during early development. These findings provide insight into the pathological mechanisms of ADHD and support the use of organoid models for studying neurodevelopmental disorders.