Cellular models to study schizophrenia: A systematic review

- Systematic review on pluripotent stem cells in schizophrenia revealed 23 published studies.
- Cell phenotypes-neural migration/proliferation/mitochondrial/synaptic abnormalities.
- Findings consistent with those from other model systems (post-mortem brain, animals, GWAS).
- Further refined study designs and combination with deep clinical phenotyping is needed.

BackgroundAdvancements in cellular reprogramming techniques have made it possible to directly study brain cells from patients with neuropsychiatric disorders. We have systematically reviewed the applications of induced pluripotent stem cells (IPSCs) and their neural derivatives in understanding the biological basis of schizophrenia.MethodWe searched the scientific literature published in MEDLINE with the following search strategy: (Pluripotent) AND (Schizophrenia OR Antipsychotic OR Psychosis). Studies written in English that used IPSCs derived from patients with schizophrenia were included.ResultsOut of 23 articles, which had used IPSCs from patients with schizophrenia, neurons or neural stem cells had been derived from them in a majority. Several parameters had been studied; the key cellular phenotypes identified included those of synaptic pathology, neural migration/proliferation deficits, and abnormal oxidative phosphorylation.ConclusionCellular modelling using IPSCs could improve the biological understanding of schizophrenia. Emerging findings are consistent with those of other study designs (post-mortem brain expression, animal studies, genome-wide association, brain imaging). Future studies should focus on refined study designs (family-based, pharmacogenomics, gene editing) and a combination of cellular studies with deep clinical phenotyping.