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Chunk #4 — Understanding neuropsychiatric disease — Challenges in research

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Pluripotent stem cells in neuropsychiatric disorders.
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Third, a paucity of model systems stifles the study of neuropsychiatric disorders. Despite the great utility of animal models in probing conserved neuronal molecular pathways and elucidating neuronal circuits, they fail to fully recapitulate any of the psychiatric disorders defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The DSM-5-defined diseases also likely represent an assortment of more circuit-specific pathologies, each triggering a related set of symptoms. Therefore, it may not be feasible to capture a given neuropsychiatric disorder in a single model organism. The limited access to disease-relevant tissue and cell types in humans represents a major obstacle toward probing disease mechanisms. To gain greater insight at the molecular level, the scientific community uses patient biopsies, cell lines and post-mortem tissue. Each of these approaches remains suboptimal for studying neuropsychiatric diseases. Biopsies of brain tissue are highly invasive, ethically problematic to obtain and yield little material. Moreover, post-mitotic neurons cannot be expanded in vitro. Commonly used cell lines do not apply to the study of neuropsychatric diseases, and only a few immortalized brain-derived cell lines