Altered cell cycle dynamics in schizophrenia

Fan, Yongjun, Abrahamsen, Greger, McGrath, John J. and Mackay-Sim, Alan (2012) Altered cell cycle dynamics in schizophrenia. Biological Psychiatry, 71 2: 129-135. doi:10.1016/j.biopsych.2011.10.004

Author Fan, Yongjun
Abrahamsen, Greger
McGrath, John J.
Mackay-Sim, Alan
Title Altered cell cycle dynamics in schizophrenia
Journal name Biological Psychiatry   Check publisher's open access policy
ISSN 0006-3223
Publication date 2012-01-15
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.biopsych.2011.10.004
Volume 71
Issue 2
Start page 129
End page 135
Total pages 7
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
Formatted abstract
The olfactory mucosa, the organ of smell in the nose, is a neural tissue that regenerates new sensory neurons throughout adult life. Based on this tissue, we previously demonstrated increased mitosis in olfactory biopsy cultures from schizophrenia patients compared with healthy control subjects. In addition, neural stem/progenitor cell cultures (neurosphere-derived cells) from nasal biopsies from individuals with schizophrenia show significantly altered gene and protein expression in key cell cycle control pathways.


The aim of this study was to investigate cell cycle dynamics in olfactory neurosphere-derived cells from nine male schizophrenia patients and nine male healthy control subjects. Cell cycles were arrested by serum deprivation after which cell population doubling time, proliferation fraction, and cell cycle period were calculated from cell counts over 96 hours. Cell cycle phase was investigated using flow cytometry. Cell lysates were analyzed for expression of cyclin proteins.


Cell population proliferation rate was increased in schizophrenia through a larger pool of proliferating progenitors and a reduced cell cycle period. All phases of the cell cycle were phase-shifted by 2 hours in the schizophrenia-derived cells, which expressed higher levels of the cyclins D1, E, and A2.


Our observations indicate that schizophrenia is associated with subtle alterations in cell cycle dynamics, shortening of the cell cycle period, and increased expression of G1/S phase cyclins. We speculate that this underlying diathesis could alter the temporal and spatial cascade of brain development and contribute to an altered neurodevelopmental trajectory in schizophrenia.
Keyword Brain development
Disease model
Neural stem cell
Olfactory epithelium
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 9 November 2011. Special issue: Functional Consequences of Altered Cortical Development in Schizophrenia.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2012 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 33 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 14 Dec 2011, 02:24:17 EST by Debra McMurtrie on behalf of Queensland Brain Institute