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Schizophr Res. 2008 Jul;102(1-3):220-9. doi: 10.1016/j.schres.2008.03.013. Epub 2008 May 5.

Olfactory physiological impairment in first-degree relatives of schizophrenia patients.

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Neuropsychiatry Division, Department of Psychiatry, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, Pennsylvania 19104, USA.



Efforts to characterize genetic vulnerability to schizophrenia are increasingly focused on the identification of endophenotypes--neurobiological abnormalities that are evident in individuals at risk. Behavioral studies have demonstrated olfactory impairments in odor detection and identification in unaffected 1st-degree relatives of schizophrenia patients, suggesting that abnormalities in this simple sensory system may serve as candidate endophenotypes. It is unclear, however, whether these behavioral abnormalities reflect basic olfactory sensory processing deficits or nonspecific disruptions of attention and cognition.


Unirhinal chemosensory olfactory evoked potentials were acquired from 14 unaffected 1st-degree relatives of schizophrenia patients and 20 healthy individuals with equivalent age and gender distributions, using 3 different concentrations of hydrogen sulfide. Subjects were also assessed behaviorally for ability to detect and identify odors.


Family members exhibited left nostril olfactory detection impairments and bilateral olfactory identification abnormalities. They had reduced evoked potential response amplitudes for the initial N1 component in the left nostril. The subsequent P2 evoked potential response was reduced bilaterally. The pattern and magnitude of family member deficits were comparable to those previously observed for schizophrenia patients.


1st-degree relatives of schizophrenia patients exhibit specific neurophysiological impairments in early olfactory sensory processing. The presence of these neurophysiological abnormalities in both schizophrenia patients and their unaffected 1st-degree relatives suggests that these represent genetically mediated vulnerability markers or endophenotypes of the illness.

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