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Childhood-Onset Schizophrenia: Insights from Induced Pluripotent Stem Cells

Anke Hoffmann1, Michael Ziller2, Dietmar Spengler3

  • 1Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany. hoffmann@psych.mpg.de.

International Journal of Molecular Sciences
|December 6, 2018
PubMed

Insights

Induced pluripotent stem cells (iPSCs) reveal cellular changes in childhood-onset schizophrenia (COS). These findings in iPSC-derived cells mirror those in diseased brain tissue, offering insights into schizophrenia

Area of Science:

  • Neuroscience
  • Genetics
  • Cell Biology

Background:

  • Childhood-onset schizophrenia (COS) is a severe psychiatric disorder with early neurodevelopmental origins.
  • Genetic factors significantly influence COS, impacting its course and long-term outcomes.
  • COS shares continuity with adult-onset schizophrenia (AOS), suggesting shared underlying mechanisms.

Purpose of the Study:

  • To review findings from induced pluripotent stem cells (iPSCs) in modeling childhood-onset schizophrenia (COS).
  • To explore how iPSC technology can elucidate the molecular and cellular underpinnings of COS.
  • To discuss the potential of iPSC-based models for improving diagnosis and treatment of COS.

Main Methods:

  • Utilizing induced pluripotent stem cells (iPSCs) from patients with COS to generate neural progenitor and neuronal cells.
  • Conducting case/control studies with iPSCs to identify genotype-specific molecular and cellular alterations.
  • Comparing transcriptional signatures of iPSC-derived cells with postmortem brain samples from schizophrenia (SCZ) patients.

Main Results:

  • iPSC-derived cells from COS patients exhibit functional alterations in dendrites, synapses, and electrical activity.
  • Key changes in glutamate signaling and miRNA expression were identified in iPSC models of COS.
  • Transcriptional profiles of iPSC-derived cells align with those found in postmortem SCZ brain samples, validating in vitro models.

Conclusions:

  • iPSC technology provides a powerful platform for studying the cellular and molecular basis of COS.
  • In vitro findings from iPSC models show promise in recapitulating in vivo pathological changes observed in schizophrenia.
  • Further research and refinement of iPSC-based disease modeling are crucial for advancing COS diagnosis and treatment.

Keywords:
childhood-onset schizophrenia (COS)copy number variation (CNV)dendritic arborizationearly neurodevelopmentinduced pluripotent stem cell (iPSC)miRNAsneuronal differentiationsynapse

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