Scents and Non-sense: Olfactory Dysfunction in Schizophrenia

Among the sensory modalities, olfaction is most closely associated with the frontal and temporal brain regions that are implicated in schizophrenia and most intimately related to the affective and mnemonic functions that these regions subserve. Olfactory probes may therefore be ideal tools through which to assess the structural and functional integrity of the neural substrates that un-derlie disease-related cognitive and emotional disturban-ces. Perhaps more importantly, to the extent that early sensory afferents are also disrupted in schizophrenia, the olfactory system—owing to its strategic anatomic location—may be especially vulnerable to such disruption. Olfactory dysfunction may therefore be a sensitive indica-tor of schizophrenia pathology and may even serve as an ‘‘early warning’ ’ sign of disease vulnerability or onset. In this article, we review the evidence supporting a primary olfactory sensory disturbance in schizophrenia. Conver-gent data indicate that structural and functional abnor-malities extend from the cortex to the most peripheral elements of the olfactory system. These reflect, in part, a genetically mediated neurodevelopmental etiology. Gross structural and functional anomalies are mirrored by cellular and molecular abnormalities that suggest decreased or faulty innervation and/or dysregulation of intracellular signaling. A unifying mechanistic hypoth-esis may be the epigenetic regulation of gene expression. With the opportunity to obtain olfactory neural tissue from live patients through nasal epithelial biopsy, the peripheral olfactory system offers a uniquely accessible window through which the pathophysiological ante-cedents and sequelae of schizophrenia may be observed. This could help to clarify underlying brain mecha-nisms and facilitate identification of clinically relevant biomarkers. Key words: neurodevelopment/genetics/biomarkers/ evoked potentials/olfactory receptor neurons/olfactory bul