Human-Derived Cellular Models in Psychiatry: A Focus on the Olfactory Neuroepithelium

Area of Science:

• Biological Psychiatry
• Neuroscience
• Genetics

Background:

• Severe mental disorders (schizophrenia, bipolar disorder, major depressive disorder) are leading causes of disability with symptomatic treatments.
• Current research points to a transdiagnostic architecture of psychopathology with shared genetic and neurodevelopmental alterations.
• Traditional models (post-mortem, imaging, animal) have limitations in accessing dynamic human neurobiology.

Purpose of the Study:

• To review cellular and tissue models in biological psychiatry.
• To examine strengths, limitations, and translational relevance of various models.
• To highlight the potential of olfactory neuroepithelium (ONE)-based models for advancing precision psychiatry.

Main Methods:

• Review of literature on cellular and tissue models in biological psychiatry.
• Analysis of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs).
• Focus on olfactory neuroepithelium (ONE)-derived neural progenitors.

Main Results:

• Human-derived iPSCs and hESCs enable in vitro study of patient-specific neurodevelopment.
• ONE models provide accessible, living human neurobiology with donor-specific signatures.
• ONE-derived cells recapitulate disease-relevant phenotypes in major psychiatric disorders.

Conclusions:

• Olfactory neuroepithelium (ONE) models show promise in bridging genetic risk, cellular dysfunction, and clinical phenotype.
• These models can advance the development of precision psychiatry.
• Further research is needed to fully leverage ONE-based models.