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.
Highlights
Neuropsychological and neuroimaging studies offer convergent evidence that schizophrenia patients have selective impairments in the functional domains of memory, attention, executive planning, and affect regulation[1,2] and have neuroanatomical and physiological abnormalities in the temporolimbic and frontal lobe regions that underlie these behavioral domains.[3]
These investigations indicate that (1) olfactory abilities are impaired in schizophrenia; (2) similar impairments are evident in individuals who are symptom free but genetically at risk; (3) these deficits may be diagnostically specific for schizophrenia as opposed to other major psychiatric conditions; and (4) they may be predictive of those high-risk individuals who will develop overt illness
The fact that ORNs exhibit continuous neurodevelopmental proliferation and can be harvested, in living subjects, through olfactory epithelial biopsy offers the possibility of testing putative mechanisms underlying the developmental neuropathology of the disorder ex vivo
Summary
Neuropsychological and neuroimaging studies offer convergent evidence that schizophrenia patients have selective impairments in the functional domains of memory, attention, executive planning, and affect regulation[1,2] and have neuroanatomical and physiological abnormalities in the temporolimbic and frontal lobe regions that underlie these behavioral domains.[3]. A similar investigation[49] examining actual psychophysical olfactory deficits, as opposed to aberrant olfactory experiences, found that odor identification performance was significantly impaired in those ‘‘high-risk’’ individuals who subsequently developed schizophrenia but not in those who went on to develop affective psychoses or remained symptom free. This finding has been recently replicated in a sample of 26 well-characterized adolescents with early onset psychosis.[50] Results revealed that deficits in odor identification existed across youths with psychotic disorder and were related to typical characteristics of schizophrenia, such as negative symptoms and lower intelligence, but not to features of bipolar disorder. The finding cited above,[49,50] that olfactory impairments during the prodromal phase significantly predict a subsequent diagnosis of schizophrenia, supports the hypothesis that this is a true disease-specific vulnerability marker
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