Using Induced Pluripotent Stem Cells to Investigate Complex Genetic Psychiatric Disorders

Abstract

Purpose of Review

Induced pluripotent stem cells (iPSCs) can be generated from human patient tissue samples, differentiated into any somatic cell type, and studied under controlled culture conditions. We review how iPSCs are used to investigate genetic factors and biological mechanisms underlying psychiatric disorders, and considerations for synthesizing data across studies.

Recent Findings

Results from patient specific-iPSC studies often reveal cellular phenotypes consistent with postmortem and brain imaging studies. Unpredicted findings illustrate the power of iPSCs as a discovery tool, but may also be attributable to limitations in modeling dynamic neural networks or difficulty in identifying the most affected neural subtype or developmental stage.

Summary

Technological advances in differentiation protocols and organoid generation will enhance our ability to model the salient pathology underlying psychiatric disorders using iPSCs. The field will also benefit from context-driven interpretations of iPSC studies that recognize all potential sources of variability, including differences in patient symptomatology, genetic risk factors, and affected cellular subtype.

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Fig. 1

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Acknowledgments

B.J.M. was partially supported by NIH (R01MH110487), the Pitt Hopkins Research Foundation, and the Brace Cove Foundation. K.M.C. was partially supported by NIH grants NS093772, NS097206, and MH106434.

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Correspondence to Kimberly M. Christian.

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Stephanie J. Temme, Brady J. Maher, and Dr. Kimberly M. Christian declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Temme, S.J., Maher, B.J. & Christian, K.M. Using Induced Pluripotent Stem Cells to Investigate Complex Genetic Psychiatric Disorders. Curr Behav Neurosci Rep 3, 275–284 (2016). https://doi.org/10.1007/s40473-016-0100-7

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Keywords

  • iPSCs
  • Schizophrenia
  • Bipolar disorder
  • Autism spectrum disorders
  • Psychiatric
  • Cellular reprogramming