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The Nose Knows Schizophrenia
Deborah Brauser – May 09, 2013
Collecting tissue samples from the nose during a simple biopsy may lead to better diagnosis of schizophrenia, new research suggests.
A small study showed that all 7 of the initial participants with schizophrenia had significantly elevated microRNA (miRNA) expression in their olfactory cells compared with the 7 participants who did not have the disorder.
Further analysis of samples captured by laser microdissecion from a cohort of 36 participants showed that the same elevated brain-enriched expression in miR-382 was found in those with schizophrenia vs those without.
“The take-home message for clinicians is that molecular markers are terrific potential candidates for complex disorders, such as those involving psychiatric symptoms,” senior author Noam Shomron, PhD, from the Department of Cell and Developmental Biology at Tel Aviv University in Israel, told Medscape Medical News.
“Further research is needed to substantiate our findings and to pinpoint whether our markers are cause or causative in this disease,” added Dr. Shomron.
Still, the investigators note that the results illustrate “the potential utility” of tissues and cells from the olfactory epithelium (OE) “as surrogate samples for the brain.”
The study is published in the July issue of Neurobiology of Disease.
Searching for Biomarkers
According to the researchers, schizophrenia biomarkers have previously been found only in the brain’s neuron cells, which can only be collected after death.
Dr. Noam Shomron
“By that point, it’s obviously too late to do the patient any good,” said Dr. Shomron in a release, noting the current importance of psychological evaluations for diagnosis.
“Psychiatric diseases were always extremely challenging to diagnose. We thought that any molecular marker would greatly impact the field of psychiatric disorders and possibly redefine the field,” Dr. Shomron noted.
For this study, investigators at Johns Hopkins University in Baltimore, Maryland, collected samples of neurons from the upper part of the inner nose from 7 outpatients with schizophrenia and from 7 participants without the disorder. Each procedure took roughly 5 minutes to perform.
In addition, OE neuronal layer-containing tissues obtained by laser-capture microdissection (LCM-OE) were assessed for a larger cohort of 36 participants, half of whom had schizophrenia.
All samples were then sent to Dr. Shomron’s laboratory at Tel Aviv University for analysis, RNA extraction, and miRNA profiling.
Invaluable for Early Diagnosis?
Results showed that the OE-derived samples from the patients with schizophrenia had significantly elevated miR-382 expression compared with samples from their healthy peers (P = .04).
As confirmed in the LCM-OE samples, “the average expression level of miR-382 was 1.64 fold higher” for those with schizophrenia compared with those who did not have the disorder (P = .02), report the researchers.
“We were able to narrow down the miRNA to a differentially expressed set, and from there down to a specific miRNA which is elevated in individuals with the disease,” said Dr. Shomron.
Further analysis showed that miR-382 “directly regulated the expression” of the FGFR1 and SPRY4 genes, which are involved in the fibroblast growth factor signaling pathway.
The overall data “suggest that miR-382 elevation detected in patients’ OE-derived samples might serve to strengthen current biomarker studies in schizophrenia,” write the investigators.
Dr. Shomron noted that the study results “were not that surprising” to him because micRNAs have been shown to be strong markers in many diseases, such as multiple types of cancer.
He also expressed optimism for this method of diagnosing schizophrenia, especially because samples can be collected during a quick and easy outpatient procedure with a local anesthetic.
Still, “it’s important to determine whether this alteration in miRNA expression begins before schizophrenic symptoms begin to exhibit themselves or only after the disease fully develops,” said Dr. Shomron.
“If this change comes near the beginning of the timeline, it could be invaluable for early diagnostics. This would mean early intervention, better treatment, and possibly even the postponement of symptoms.”
A full list of study funders can be found in the original article. The study authors have reported no relevant financial relationships.
Neurobiol Dis. 2013;55:1-10. Abstract