Diminished gating of the P50 auditory evoked response to repeated stimuli is a psychophysiological feature of schizophrenia, that is also present in many relatives of patients.
Deficits in gating of the P50 response have been shown to segregate with schizophrenia in this sample and may identify carriers of gene(s) predisposing for schizophrenia.
We have used a previously characterized neurophysiological variable, the P50 evoked-auditory response, to search for chromosomal regions that may be of interest in the study of schizophrenia.
The defect, a decrease in the normal inhibition of the P50 auditory-evoked response to the second of paired stimuli, is associated with attentional disturbances in schizophrenia.
Adult-onset schizophrenia is generally associated with one parent who demonstrates abnormal P50 sensory gating and elevated anticipatory saccades and one parent who is normal on the physiologic measures (i.e., unilineal inheritance).
The initial study showing linkage of the P50 deficit to the chromosome 15q14 locus of the alpha 7-nicotinic acetylcholine receptor is an example of the potential usefulness of these phenotypes for combined genetic and neurobiological study of schizophrenia.
Deficits in P50 suppression have high heritability and show linkage to the alpha-7 subunit of the nicotinic cholinergic receptor gene in families with schizophrenia, suggesting that deficits in P50 suppression are trait markers for gating abnormalities in schizophrenia spectrum subjects.
A deficit in the inhibition of the P50 evoked response to repeated auditory stimuli has been characterized as a neurobiological deficit in schizophrenia.
The nicotinic system has previously been studied in schizophrenia where the neuronal nicotinic acetylcholine receptor alpha 7 subunit gene (CHRNA7) has been implicated in decreased P50 inhibition and attentional disturbances in patients with schizophrenia and in many of their nonschizophrenic relatives.
Results show excess allele sharing for multiple markers in 15q11.2-q25, a chromosomal region previously found linked to a decrease in the normal inhibition of the P50 auditory-evoked response to the second of paired stimuli, a decrease associated with schizophrenia.
A paired-stimulus auditory event- related potential paradigm was used to examine P50 sensory gating in 85 schizophrenia patients (56 medicated with typical antipsychotics and 29 unmedicated), 83 of their first-degree relatives (46 parents and 37 siblings), and 29 normal comparison subjects.
A number of studies have suggested that the alpha-7-nicotinic receptor D15S1360 polymorphism is associated with schizophrenia and a deficiency in the normal inhibition of the P50 auditory-evoked response.
Subjects with schizophrenia and half their first-degree relatives have deficits in sensory gating, with P50 ratios that are generally greater than 50%.
Because P50 sensory gating deficit is a common neurophysiological dysfunction in patients with schizophrenia and schizophrenia spectrum disorders, it is conceivable to hypothesize that the human alpha7 neuronal nicotinic receptor subunit gene might be a susceptible gene for schizophrenia.
We found that, despite the prominent role that P50 abnormalities have played in our understanding of schizophrenia, there is a relative dearth of data examining P50 clinical correlates.