Mental health disorders (MHDs) commonly have a neurodevelopmental origin, therefore elucidating the expression of MHD risk genes during early brain development is crucial for understanding disease pathogenesis. Almost all human genes produce multiple RNA isoforms, especially in the brain where switches between alternative RNA isoforms with distinct functions govern many aspects of brain development and physiology. While neuropsychiatric risk genes have been increasingly identified, few studies have focused on the role of alternative risk gene isoforms and how they are associated with healthy brain development or disease accumulation. To address the knowledge gap, we employed human pluripotent stem cells (hPSCs)-derived cortical neurons and cerebral organoids to recapitulate the early stages of healthy human brain development. Leveraging the power of nanopore long-read RNA sequencing technology, we aimed to construct comprehensive and dynamic risk gene isoform profiles that spanned up to six months of brain development. By integrating the obtained data, we revealed the isoform characteristics of seven well-established MHD risk genes at multiple timepoints throughout the developmental process. Among the 233 isoforms identified, 202 were novel, collectively constituting half the total gene expression, indicating the high diversity and prevalence of novel isoforms in developing brains. Additionally, isoform usage in fetal brain models often exhibites markedly different profiles from those of adult brains. These isoform proportions change dynamically across developmental timepoints, as exemplified by CLCN3 and MAPT, suggesting active regulation throughout development. Notably, genes often have highly expressed novel isoforms, such as those from RBFOX1 and MAPT, with MAPT’s dominant isoform unique to fetal brain models, implying a specific function in neurodevelopment. Our findings underscore the underestimated complexity of isoform expression in developing brains. Investigating risk gene isoforms in a neurodevelopmental context is crucial for understanding MHD origins and may provide insights into molecular mechanisms and potential therapeutic targets.