Major programs in psychiatric genetics have identified >150 risk loci for psychiatric disorders. These loci converge on a small number of functional pathways, which span conventional diagnostic criteria, suggesting a partly common biology underlying schizophrenia, autism and other psychiatric disorders. Nevertheless, the cellular phenotypes that capture the fundamental features of psychiatric disorders have not yet been determined. Recent advances in genetics and stem cell biology offer new prospects for cell-based modeling of psychiatric disorders. The advent of cell reprogramming and induced pluripotent stem cells (iPSC) provides an opportunity to translate genetic findings into patient-specific in vitro models. iPSC technology is less than a decade old but holds great promise for bridging the gaps between patients, genetics and biology. Despite many obvious advantages, iPSC studies still present multiple challenges. In this expert review, we critically review the challenges for modeling of psychiatric disorders, potential solutions and how iPSC technology can be used to develop an analytical framework for the evaluation and therapeutic manipulation of fundamental disease processes.

Department Clinical Genetics Vrije Universiteit Medical Center Neuroscience Campus Amsterdam Amsterdam The Netherlands

Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic

Department of Complex Trait Genetics Center for Neurogenomics and Cognitive Research Vrije Universiteit Amsterdam Amsterdam The Netherlands

Department of Genetics University of North Carolina Chapel Hill NC USA

Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden

Department of Medical Genetics Oslo University Hospital University of Bergen Oslo Norway

Department of Molecular Medicine University of Oslo and Norwegian Center for Stem Cell Research Oslo University Hospital Oslo Norway

Department of Neuroscience Karolinska Institutet Stockholm Sweden

Department of Pediatrics Child Neurology VU University Medical Center Amsterdam Amsterdam The Netherlands

Department of Psychiatry University of North Carolina Chapel Hill NC USA

Institute of Reconstructive Neurobiology LIFE and BRAIN Center University of Bonn and German Center for Neurodegenerative Diseases Bonn Germany

Neuroscience and Mental Health Research Institute and School of Biosciences Cardiff University Cardiff UK

NORMENT KG Jebsen Centre for Psychosis Research Department of Clinical Science University of Bergen Bergen Norway

Regenerative Medicine Institute School of Medicine NUI Galway Galway Ireland

Erratum In

Mol Psychiatry. 2016 Sep;21(9):1321. doi: 10.1038/mp.2016.100. PubMed

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