Induced Pluripotent Stem Cells in Psychiatry: An Overview and Critical Perspective

Alejandro De Los Angeles, Michael B. Fernando, Nicola A.L. Hall, Kristen J. Brennand, Paul J. Harrison, Brady J. Maher, Daniel R. Weinberger, Elizabeth M. Tunbridge

Research output: Contribution to journalReview articlepeer-review

10 Scopus citations


A key challenge in psychiatry research is the development of high-fidelity model systems that can be experimentally manipulated to explore and test pathophysiological mechanisms of illness. In this respect, the emerging capacity to derive neural cells and circuits from human induced pluripotent stem cells (iPSCs) has generated significant excitement. This review aims to provide a critical appraisal of the potential for iPSCs in illuminating pathophysiological mechanisms in the context of other available technical approaches. We discuss the selection of iPSC phenotypes relevant to psychiatry, the information that researchers can draw on to help guide these decisions, and how researchers choose between the use of 2-dimensional cultures and the use of more complex 3-dimensional model systems. We discuss the strengths and limitations of current models and the challenges and opportunities that they present. Finally, we discuss the potential of iPSC-based model systems for clarifying the mechanisms underlying genetic risk for psychiatry and the steps that will be needed to ensure that robust and reliable conclusions can be drawn. We argue that while iPSC-based models are ideally placed to study fundamental processes occurring within and between neural cells, they are often less well suited for case-control studies, given issues relating to statistical power and the challenges in identifying which cellular phenotypes are meaningful at the level of the whole individual. Our aim is to highlight the importance of considering the hypotheses of a given study to guide decisions about which, if any, iPSC-based system is most appropriate to address it.

Original languageEnglish
Pages (from-to)362-372
Number of pages11
JournalBiological Psychiatry
Issue number6
StatePublished - 15 Sep 2021


  • Bipolar disorder
  • Drug screening
  • Model system
  • Neuron
  • Pathophysiology
  • Schizophrenia


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