title: Disease signatures for schizophrenia and bipolar disorder using patient-derived induced pluripotent stem cells.
abstract: Schizophrenia and bipolar disorder are complex psychiatric disorders that present unique challenges in the study of disease biology. There are no objective biological phenotypes for these disorders, which are characterized by complex genetics and prominent roles for gene-environment interactions. The study of the neurobiology underlying these severe psychiatric disorders has been hindered by the lack of access to the tissue of interest - neurons from patients. The advent of reprogramming methods that enable generation of induced pluripotent stem cells (iPSCs) from patient fibroblasts and peripheral blood mononuclear cells has opened possibilities for new approaches to study relevant disease biology using iPSC-derived neurons. While early studies with patient iPSCs have led to promising and intriguing leads, significant hurdles remain in our attempts to capture the complexity of these disorders in vitro. We present here an overview of studies to date of schizophrenia and bipolar disorder using iPSC-derived neuronal cells and discuss potential future directions that can result in the identification of robust and valid cellular phenotypes that in turn can lay the groundwork for meaningful clinical advances.
authors.affiliation: Center for Experimental Drugs and Diagnostics, Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, United States; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, United States; Center for the Science of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, United States.
authors.forename: Bradley
authors.initials: B
authors.lastname: Watmuff
authors.affiliation: Center for Experimental Drugs and Diagnostics, Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, United States; Center for the Science of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, United States.
authors.forename: Shaunna S
authors.initials: SS
authors.lastname: Berkovitch
authors.affiliation: Center for Experimental Drugs and Diagnostics, Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, United States; Center for the Science of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, United States.
authors.forename: Joanne H
authors.initials: JH
authors.lastname: Huang
authors.affiliation: Center for Experimental Drugs and Diagnostics, Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, United States; Center for the Science of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Iaconelli
authors.affiliation: Center for Experimental Drugs and Diagnostics, Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, United States; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, United States; Center for the Science of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, United States.
authors.forename: Steven
authors.initials: S
authors.lastname: Toffel
authors.affiliation: Center for Experimental Drugs and Diagnostics, Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, United States; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, United States; Center for the Science of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, United States; Schizophrenia and Bipolar Disorder Program, McLean Hospital, Belmont, MA 02478, United States. Electronic address: karmacharya@mgh.harvard.edu.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Karmacharya
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018929:Cell Culture Techniques / Q000379:methods*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008954:Models, Biological; D010641:Phenotype; D057285:Precision Medicine / Q000379:methods; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
keywords: Bipolar disorder; Gene–environment; IPSC; Microglia; Neuronal differentiation; Schizophrenia; Stem cells