Olfactory neuroepithelium alterations and cognitive correlates in schizophrenia

Abstract

BackgroundFew studies have investigated alterations of olfactory neuroepithelium (ONE) as a biomarker of schizophrenia, and none its association with cognitive functioning. MethodFresh ONE cells from twelve patients with schizophrenia and thirteen healthy controls were collected by nasal brushing, cultured in proper media and passed twelve times. Markers of cell proliferation (BrdU incorporation, Cyclin-D1 and p21 protein level) were quantified.Cognitive function was measured using Brief Neuropsychological Examination-2. Primary outcome: proliferation of ONE cells from schizophrenic patients at passage 3. Secondary outcome: association between alteration of cell proliferation and cognitive function. ResultsFresh ONE cells from patients showed a faster cell proliferation than those from healthy controls at passage 3. An opposite trend was observed at passage 9, ONE cells of patients with schizophrenia showing slower cell proliferation as compared to healthy controls. In schizophrenia, overall cognitive function (Spearman’s rho -0.657, p < 0.01), verbal memory – immediate recall, with interference at 10 s and 30 s (Spearman’s rho from -0.676 to 0.697, all p < 0.01) were inversely associated with cell proliferation at passage 3. ConclusionFresh ONE cells collected by nasal brushing might eventually represent a tool for diagnosing schizophrenia based upon markers of cell proliferation, which can be easily implemented as single-layer culture. Cell proliferation at passage 3 can be regarded as a promising proxy of cognitive functioning in schizophrenia. Future studies should replicate these findings, and may assess whether ONE alterations are there before onset of psychosis, serving as an early sign in patients with at risk mental state.