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Mol Psychiatry. 2016 Sep;21(9):1167-79. doi: 10.1038/mp.2016.89. Epub 2016 May 31.

Modeling psychiatric disorders: from genomic findings to cellular phenotypes.

Author information

1
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
2
Department of Pediatrics/Child Neurology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
3
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
4
Neuroscience and Mental Health Research Institute & School of Biosciences, Cardiff University, Cardiff, UK.
5
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
6
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
7
Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
8
Institute of Reconstructive Neurobiology, LIFE & BRAIN Center, University of Bonn and German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
9
Regenerative Medicine Institute, School of Medicine, NUI Galway, Galway, Ireland.
10
Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
11
Department of Molecular Medicine, University of Oslo, and Norwegian Center for Stem Cell Research, Oslo University Hospital, Oslo, Norway.
12
Department Clinical Genetics, Vrije Universiteit Medical Center, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
13
Department of Medical Genetics, Oslo University Hospital, University of Bergen, Oslo, Norway.
14
NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway.

Abstract

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.

PMID:
27240529
PMCID:
PMC4995546
DOI:
10.1038/mp.2016.89
[Indexed for MEDLINE]
Free PMC Article

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