Commentary| Volume 93, ISSUE 7, P588-589, April 01, 2023

Neural Organoids and the Quest to Understand and Treat Psychiatric Disease

      Progress in understanding the molecular mechanisms underlying human psychiatric disease has been hampered by a lack of models that can reflect the genetic states underlying human cognitive disease and species-specific differences in brain development and function. This is particularly true of sporadic forms of psychiatric disease, which account for most cases; these cases are often associated with the cumulative contribution of multiple common risk variants, each with small effects—a type of genetic structure that is difficult or impossible to replicate in animal models. Human-derived induced pluripotent stem cells are a revolutionary advance for the study of the contribution of the broader genomic landscape to disease states, and the emergence of 3-dimensional brain organoid models has opened a new window to investigate the cellular and molecular underpinnings of human brain development and disease. In this special issue of Biological Psychiatry, leaders in this field offer their perspectives on the use of human organoid models to understand psychiatric disease.
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        • Zhang Z.
        • Wang X.
        • Park S.
        • Song H.
        • Ming G.-L.
        Development and application of brain region–specific organoids for investigating psychiatric disorders.
        Biol Psychiatry. 2023; 93: 594-605
        • Urenda J.-P.
        • Del Dosso A.
        • Birtele M.
        • Quadrato G.
        Present and future modeling of human psychiatric connectopathies with brain organoids.
        Biol Psychiatry. 2023; 93: 606-615
        • Puppo F.
        • Muotri A.R.
        Network and microcircuitry development in human brain organoids.
        Biol Psychiatry. 2023; 93: 590-593
        • Wang M.
        • Gage F.H.
        • Schafer S.T.
        Transplantation strategies to enhance maturity and cellular complexity in brain organoids.
        Biol Psychiatry. 2023; 93: 616-621
        • Wang L.
        • Owusu-Hammond C.
        • Sievert D.
        • Gleeson J.G.
        Stem cell–based organoid models of neurodevelopmental disorders.
        Biol Psychiatry. 2023; 93: 622-631
        • Levy R.J.
        • Paşca S.P.
        What have organoids and assembloids taught us about the pathophysiology of neuropsychiatric disorders?.
        Biol Psychiatry. 2023; 93: 632-641
        • Seah C.
        • Huckins L.M.
        • Brennand K.J.
        Stem cell models for context-specific modeling in psychiatric disorders.
        Biol Psychiatry. 2023; 93: 642-650