What Have Organoids and Assembloids Taught Us About the Pathophysiology of Neuropsychiatric Disorders?

Neuropsychiatric research has been impeded by limited access to human brain tissue, especially from early stages of neurodevelopment when the pathophysiology of many childhood-onset disorders is initiated. Neural organoids are 3-dimensional, self-organizing, multicellular structures generated from pluripotent stem cells that recapitulate some of the cell diversity, cytoarchitecture, and functional features of domains of the developing nervous system. Assembloids are 3-dimensional, self-organizing cultures created by the combination of two or more distinctly patterned organoids or an organoid plus additional cell or tissue type(s) that are used to model cell migration and connectivity. Here we review recent advances in neuropsychiatric disorder research using organoid and assembloid models to study the role of disease-relevant genes and mutations, as well as the impact of environmental risk factors on neural development. We also highlight some of the advantages and limitations of these model systems in bringing insights into the pathophysiology of neuropsychiatric disorders.