Olfactory physiological impairment in first-degree relatives of schizophrenia patients

Abstract

Background-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 1 st -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.Method-Unirhinal chemosensory olfactory evoked potentials were acquired from 14 unaffected 1 st -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.Results-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.Conclusion-1 st -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 1 st -degree relatives suggests that these represent genetically mediated vulnerability markers or endophenotypes of the illness.

Olfaction, psychiatric disorders and autoimmunity: Is there a common genetic association?

“…Lower baseline UPSIT scores in newly diagnosed schizophrenic patients might be used to predict a worse disease prognosis [57]. Nonpsychotic relatives of schizophrenic patients also had odor deficits, which were more severe in ones with schizotypal personality, a finding that supports a genetic vulnerability [58,59]. These findings support the hypothesis of a primary olfactory dysfunction in the pathogenesis of some psychiatric manifestations.…”

Why endophenotype development requires families

“…Indeed, other areas of perception or information processing (e.g. olfaction function [25]) or blood-based assays (e.g. [26]) could prove important measures of genetic liability for mental illness and help to delineate the genes and gene systems that predispose these illnesses.…”

Human Olfactory Perception

“…212 First-degree relatives of schizophrenia patients exhibit specific impairments in odorant-elicited olfactory evoked potentials. 213 Recordings of the electroolfactogram from the olfactory epithelium of schizophrenic patients suggest a role for altered sensory processing in the olfactory deficits of these patients. 214 Depressive symptoms in general can be related to a reduced olfactory sensitivity.…”

“…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. 221 Recent psychophysical evidence implicates a deficit in intracellular cyclic adenosine monophosphate (cAMP) signalling in schizophrenic patients as a causative factor in olfactory dysfunction.…”