Mirnics and colleagues have provided a compelling case for the utility of DNA microarrays in psychiatric research. They also draw attention to the pitfalls of using postmortem and non-neural tissues for gene expression studies in psychotic disease (i.e., heterogeneity of diagnosis, treatment, genetic background, postmortem interval, and molecular differences between neural and non-neural tissues). However, the options for obtaining living neural tissues from psychiatric patients and healthy controls are very limited. Mirnics and colleagues noted that tissue derived from biopsy of the olfactory neuroepithelium (Féron et al., 1999) may provide “an excellent and underutilized source of tissue for high-throughput expression profiling experiment.”
We are pleased to report the first application of gene expression microarrays to human olfactory epithelium in schizophrenia and bipolar I disorder (McCurdy et al., 2006). Reassuringly, several of the genes we found to be differentially expressed in schizophrenia belonged to molecular pathways previously shown to be affected in schizophrenia (e.g., synaptic function and mitochondrial and nucleic acid metabolism) or were supportive of our finding of altered cell cycle in cultures of olfactory neuroepithelium from individuals with schizophrenia. Similarly, there were consistencies with our bipolar I disorder expression data and previously reported findings (i.e., decreased expression of GNAZ, ARGHEF2, APC, and PLCD1 mRNA transcripts).
Apart from assessing the transcriptome in biopsied olfactory neuroepithelium, this tissue also contains a stem cell that can be isolated and manipulated to differentiate into multiple cell types (e.g., neuron, glial cells) (Murrell et al., 2005). Comparing the patterns of gene expression during neuronal differentiation between patients versus well controls could provide valuable insights into aetiopathogenesis of the various neuropsychiatric disorders.
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2. McCurdy RD, Feron F, Perry C, Chant DC, McLean D, Matigian N, Hayward NK, McGrath JJ, Mackay-Sim A. Cell cycle alterations in biopsied olfactory neuroepithelium in schizophrenia and bipolar I disorder using cell culture and gene expression analyses.
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3. Murrell W, Feron F, Wetzig A, Cameron N, Splatt K, Bellette B, Bianco J, Perry C, Lee G, Mackay-Sim A. Multipotent stem cells from adult olfactory mucosa. Dev Dyn. 2005 Jun;233(2):496-515. Abstract
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