Recordings were completed and analyzed from 333 healthy community comparison controls, 181 probands with schizophrenia, and 429 of their first degree relatives. The proportion of analyzed recordings, after exclusion of recordings with artifacts, ranged from 66% to 77% from each site, mean 71% ± 3% (s.d.), and was not significantly different across sites. The proportion of analyzed recordings was also similar across the three subject groups: 74% in the controls, compared to 69% in both the probands with schizophrenia and their relatives. shows demographic variables. Relatives were significantly older because of the inclusion of parents. Probands were less likely to be female, had less education, and were more likely to smoke.
Demographic variables in the community comparison control subjects, probands with schizophrenia, and their first degree relatives
3.1. Differences in physiological parameters between groups
Significant differences were found between groups for P50 ratio in a mixed model analysis of variance that included group, site, years of education, gender, age, and smoking status as fixed variables and family as a random variable. There was a significant effect for group (F = 20.82, df 2, 760, P <0.0001). The estimated P50 ratio least square mean for controls was 0.37 ± 0.02 (s.e.). For probands it was 0.62 ± 0.04 (s.e.), and for relatives it was 0.49 ± 0.02 (s.e.). The comparison of controls and probands was highly significant (t = 5.75, df 760, P < 0.0001). The controls also differed from the relatives (t = 4.54, df 760, P = 0.0003). The probands and relatives were less significantly different (t = 2.52, df 760, P = 0.01).
Analysis of variance for each component of the response showed a modest effect of group for conditioning amplitude (F = 3.80, df 2, 760, P = 0.02) and a more significant effect for test amplitude (F = 7.94, df 2, 760, P = 0.0004). The difference between the components (conditioning amplitude − test amplitude) also showed a significant group effect (F = 16.14, df 2, 760, P < 0.0001). Means and standard deviations for all parameters are shown in .
P50 amplitudes in response to paired auditory stimuli
The effect size for distinguishing P50 parameters in schizophrenia from the controls was 0.57 for the ratio of the amplitudes, 0.49 for their difference, 0.23 for the conditioning amplitude alone, and 0.32 for the test amplitude alone. Pearson's correlations were performed to explore relationships between these parameters. The conditioning and the test amplitude were themselves correlated with each other (r = 0.61).
The ratio of the amplitudes was correlated with the difference between the amplitudes (r = −0.64). The conditioning amplitude was marginally correlated with the ratio of the amplitudes (r = −0.14), whereas it was more highly correlated with the difference between the amplitudes (r = 0.77). The test amplitude was more highly correlated with the ratio of the amplitudes (r = 0.58) than with their difference (r = −0.03).
There were no significant correlations between P50 parameters and clinical ratings.
3.2. Evidence for admixture of the physiological deficit in families with schizophrenia
Both the difference and ratio parameters are significantly different in first degree relatives compared to controls, and both parameters have values that are approximately halfway between the values for the probands and the controls, consistent with the relatives' predicted sharing of 50% of any abnormal genes related to schizophrenia. However, the distributions of individual values in the three groups are quite different for the two parameters. For the ratio of amplitudes, the controls formed an apparently homogeneous group. The probands could be divided into two groups by the admixture analysis, with the group resembling controls comprising 39% of the probands and the other 61% in a higher range (Chi-square = 12.4, df 1, P = 0.0004). Among the first degree relatives, 63% resembled the controls and 37% resembled the probands (Chi-square = 13.0, df 1, P = 0.0003). is a histogram of values for all three groups, with the distributions derived from admixture analysis. The difference parameter was homogeneous in all three groups, with no significant evidence for admixture.
Figure 1 Auditory evoked responses as recorded at the vertex (EEG) and near the eye (EOG) in response to paired auditory stimuli (arrowheads) from a control subject and from a schizophrenia proband. The P50 was identified by a computer algorithm and measured relative (more ...)
The parents (N = 139) were compared with the siblings (N = 289). The two groups did not differ on P50 ratio (0.50 ± 0.39 (s.d.) for parents and 0.50 ± 0.32 for siblings) or the difference between P50 amplitudes (1.51 ± 1.3 for parents and 1.72 ± 1.5 for siblings).