Abstract
Olfactory impairments are a common feature of schizophrenia. Impairments in odor detection and odor identification are present early in the course of illness and among those at risk for the disorder. These behavioral impairments have been linked to both physiological and anatomical abnormalities in the neural substrates subserving olfaction, including relatively peripheral elements of the olfactory system. The location of olfactory receptor neurons in the nasal epithelium allows noninvasive access to these neurons in living subjects. This offers a unique opportunity to directly assess neuronal integrity in vivo in patients. The peripheral olfactory receptor neuron response to odor stimulation was assessed in 21 schizophrenia patients and 18 healthy comparison subjects. The electroolfactogram, representing the electrical depolarization of the olfactory receptor neurons, was recording following stimulation with different doses and durations of hydrogen sulfide, a pure olfactory nerve stimulant. Schizophrenia patients had abnormally large depolarization responses following odor stimulation, independent of clinical symptomatology, antipsychotic medication dosage or smoking history. Although the precise pathophysiological mechanism is unknown, this olfactory receptor neuron abnormality is consistent with several lines of evidence suggesting altered proliferation or maturation of olfactory receptor neuron cell lineages in schizophrenia. It is also consistent with emerging evidence of disruptions of cyclic AMP-mediated intracellular signaling mechanisms, and may be a marker of these disruptions. It unambiguously demonstrates that neurophysiological disturbances in schizophrenia are not limited to cortical and subcortical structures, but rather include even the most peripheral sensory neurons.
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Acknowledgements
We thankfully acknowledge the advice and guidance of Dr Richard L Doty and Dr Raquel E Gur, and the assistance in data collection of Ms Kiana Owzar, Mr David Roalf, and Mr Charles Glass.
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This work was supported by NIH grant MH0599852 awarded to Dr Turetsky. None of the authors have potential conflicts of interest relevant to the subject matter of the article. None of the authors have received, or anticipate receiving, compensation for professional services from any organization other than the University of Pennsylvania.
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Turetsky, B., Hahn, CG., Arnold, S. et al. Olfactory Receptor Neuron Dysfunction in Schizophrenia. Neuropsychopharmacol 34, 767–774 (2009). https://doi.org/10.1038/npp.2008.139
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DOI: https://doi.org/10.1038/npp.2008.139
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