Introduction 20 23 39 43 . 41 58 11 14 40 24 52 16 47 10 12 37 38 47 48 56 53 28 36 33 18 42 33 47 19 4 9 33 47 33 47 57 10 33 13 21 27 49 2 49 5 32 54 30 5 11 14 32 Methods Subjects 26 37 1 2 51 Table 1 Education level of probands and controls  Probands with genetic risk Controls School type Lerning-Disabled School  1 1 Secondary School 15 14 Grammer School/Advanced  Technical College/University 10/3 13/2 Technical College/Vocational School 3 2 Education level of the parents (always the highest qualification) Secondary School 3 1 Technical College/Vocational School 17 17 Advanced Technical College/University 12 14 Groups did not differ significantly  Table 2 Demographic characteristics of probands  Demographic data Subjects Probands with genetic risk Controls Age (years) 16.0 ± 2.4 16.2 ± 2.0 Gender (male/female) 13/19 13/19 Intelligence (SPM-IQ) Non verbal IQ 101.6 ± 13.8 100.5 ± 9.7 Data of age and intelligence as mean values ± standard deviation Groups did not differ significantly Diagnostic screening and evaluation 8 31 44 Neuropsychological evaluation 22 1 46 3 Results  The primary aim of the data analysis was to evaluate group differences for the parameters described above and to examine connections between the variables. Therefore, we tested our hypothesis that the genetic risk group of unaffected children and siblings of schizophrenics would perform more poorly on the tests than would healthy controls. Furthermore, we assumed that relatives of schizophrenics would show a wider pattern of impairments than would healthy controls. All statistical analysis were done using SPSS software (version 10.1). U t 3 4 Table 3 Comparison of neuropsychological data between high risk and control probands Neuropsychological variable Subjects Comparisons n n p WCST PCT, Percentage of correct trials 77.7 ± 10.5 84.0 ± 6.1 0.002+ PPE, Percentage of perseverative errors 9.8 ± 3.5 7.9 ± 2.8 0.010 NC, Number of complete categories 5.7 ± 0.8 6.0 ± 0.2 0.042* FWIT A, Working speed  47.6 ± 8.0 52.2 ± 6.3 0.012 N, Naming skill 49.5 ± 7.0 49.0 ± 8.3 ns S, Selectivity skill 54.7 ± 7.1 55.5 ± 8.4 ns E, Number of errors during the interference task 14.9 ± 6.3 9.8 ± 5.1 0.000* TMT A, Time to execute TMT part A 35.3 ± 10.6 27.8 ± 9.9 0.002 B, Time to execute TMT part B 83.0 ± 32.6 63.0 ± 18.6 0.002 E, Number of errors 0.47 ± 1.02 0.25 ± 0.57 ns* A/B, Ratio of times of part A to B 0.462 ± 0.167 0.452 ± 0.121 ns d2 GZ, Number of treated signs 396.7 ± 97.7 448.9 ± 92.1 0.016 FGZ, Rate of errors to number of treated signs 3.6 ± 2.1 3.1 ± 2.9 ns ns, Non-siginficant differences t U + p Table 4 n  WCST FWIT TMT D2 PCT Errors Action  A GZ WCST PCT, Percentage of correct trials  −0.354** 0.316* −0.357** −0.387** FWIT Errors −0.354**  −0.471** 0.347** −0.331** Action, Speed of a general alertness 0.316* −0.471**  −0.416** 0.627** TMT A, Time to execute TMT part A as an inverse indicator of working speed −0.357** 0.347** −0.416**  −0.463** d2 GZ, Number of treated signs as an indicator of working speed 0.387** −0.331** 0.627** −0.463**  *Correlation two-sited significant at the level of 0.05  **Correlation two-sited significant at the level of 0.01  Group differences Compared to the controls, first-degree relatives of schizophrenic patients were significantly impaired in their performance on certain parts of all tests. For the WCST variables “percentage of correct trials” (PCT), “percentage of perseverative errors” (PPE), and “number of complete categories” (NCC), the analysis showed significantly worse results in the index group. The second finding of the three tests with time-limited demands, the FWIT, TMT, and d2-test, was that subjects with a genetic risk for schizophrenia worked at a significant slower rate as compared to the controls. Even though the variance of the significant results is greater in the high-risk group, these differences are not caused by extreme values. Statistical differences between the groups could not be detected for error rate on the TMT or on the d2, for cognitive control and flexibility or for naming skills on the FWIT (FWIT/N). However, first-degree relatives of schizophrenic patients produced significantly more mistakes on the interference task of the FWIT as compared to their controls. Effects of age, intelligence and gender 17 55 Relationships between variables  The correlation between working speed and all time-limited tests (FWIT, TMT, d2) was highly significant, as was the correlation between speed and the PCT during the WCST. There is a positive connection between the accuracy of the d2 and the TMT. However, only the accuracy of the interference task on the FWIT correlated to parts of the WCST scores and the working speeds on the FWIT, TMT, and d2. While speed on the TMT is lower in the index group, there was no difference between the two groups regarding the ratio of the times required to complete the TMT/A and the TMT/B. Variable naming correlated only with general alertness on the FWIT. And selectivity on the FWIT did not correlate with any other performance variable. Additionally, we did some factor analyses to see if different cognitive test variables could reflect the same cognitive function or a general vulnerability for schizophrenia. Surprisingly, after orthogonal rotation we found three factors explaining almost 60% of variance. But the other 4 of 7 components had “Eigenwerte” between 0.55 and 0.97, so that we found almost as many factors as variables. After graphic representation, we are very cautious with an interpretation of the results of this factor analyses. Discussion This study examined the hypothesis that children and siblings of patients with schizophrenia, without a schizophrenic-spectrum disorder, show a pattern of decreased attentional and cognitive performance when compared to controls. Several findings of this study can be emphasized. First, subjects at risk for schizophrenia were slower on all three time-limited tests; the FWIT, TMT, and d2. These results suggest that young persons with a genetic risk need much more time to achieve the same accuracy as the controls during routine work on the d2 and the TMT/A. The correlations among working speeds for all time-limited tests indicate that these tests assess the same components of an attentional process and that this may reflect a general vulnerability. On the other hand, on tasks with no time structure or constraints high risks showed a lower ability to establish, maintain or adjust a required conceptual level during the WCST. This finding suggests impaired executive functions, working memory, vigilance and cognitive flexibility, which cannot be compensated by using more time, as compared to the controls. Furthermore, it is fair to assume that parameters of the prolonged and more complex tasks of the WCST measure different cognitive processes than do those of the time-limited tests. Nevertheless, there are correlations between WCST-scores and other scores, especially regarding working speed. 50 Third, our findings regarding cognitive flexibility and naming skills on the FWIT are not reflected in the working speed for all time-limited tasks or in the intelligence of the probands. There is no correlation between these variables. However, there are significant correlations between the accuracy of the interference task on the FWIT with both the working speed for all time-limited tasks, as well as with WCST performance. Thus, both groups needed the same time to perform the interference task on the FWIT, but the high-risk probands made more mistakes. This is an indicator of impaired selectivity in distinguishing relevant from irrelevant stimuli. The results of the TMT test can be attributed to an impaired action speed but not to a lower ability of cognitive adjustment. Thus, the results do not allow a clear comparison of selectivity and naming performance in both groups. Probably the FWIT subtests, with their demands on naming and cognitive adjustment, reflect other aspects of the attentional process as compared to other parts of the tests used. 28 33 33 56 10 33 15 34 6 7 25 29 35 45