Scents and Nonsense: Olfactory Dysfunction in Schizophrenia

Abstract

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 underlie disease-related cognitive and emotional disturbances. 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 indicator 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. Convergent data indicate that structural and functional abnormalities 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 hypothesis 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 antecedents and sequelae of schizophrenia may be observed. This could help to clarify underlying brain mechanisms and facilitate identification of clinically relevant biomarkers.

Olfactory function and morphology of olfactory epithelium in an adult population with schizophrenia

“…Recently Kastner et al (2013) could not see a negative influence of smoking on central olfactory measures in a huge patient group with SZ. However, the influence of smoking and olfactory function in SZ remains controversial, since this potential factor was not consistently investigated in recent studies (Turetsky et al, 2009b). Interestingly, and in contrast to most recent reports (Brewer and Pantelis, 2010), we found no impairment in odor identification in the SZ group relative to healthy controls.…”

Disease-specific, neurosphere-derived cells as models for brain disorders

“…With evidence for disease-related alterations in olfactory epithelium and the loss of olfaction that is associated with many neurological diseases, including SZ and PD (Brewer et al, 2003;Doty, 2009;Haehner et al, 2009;Turetsky et al, 2009), we hypothesized that olfactory mucosal stem cells derived from SZ and PD patients would provide an accessible, proliferating population to investigate the cellular bases of these diseases (Mackay-Sim and Silburn, 2008). We predicted that olfactory neurosphere-derived (ONS) cells would exhibit disease-specific alterations in these two unrelated neurological and neuropsychiatric disorders: SZ, a highly heritable neurodevelopmental condition (Raedler et al, 1998), and PD, a neurodegenerative disease that is heritable in only about 5% of familial cases (Lesage and Brice, 2009).…”

Human Olfactory Perception

“…216 Human immunodeficiency virus (HIV) infection is associated with a decrease in olfactory ability 217 that is likely due, at least in part, to rhinosinusitis commonly associated with HIV infection. 218 Olfactory dysfunction is clearly associated with schizophrenia, 219 as evidenced by studies of both schizophrenic patients and their first-degree relatives. 213 A component of altered olfactory function in schizophrenic patients is due to altered function of olfactory receptors, as assessed by both in situ odour-evoked electro-olfactogram recordings, 214 olfactory event-related potentials 220 and studies of fresh biopsy samples of the olfactory epithelium.…”