Relative risk of attention deficits in siblings of patients with schizophrenia.
OBJECTIVE
Impaired attention has frequently been observed in studies of unaffected siblings of patients with schizophrenia. To assess the suitability of impaired attention for use as an intermediate phenotype in genetic studies, the authors estimated the relative risk of impaired attention in a large group of siblings.


METHODS
The authors used the Continuous Performance Test, 1-9 version, with and without a distraction condition, to study 147 patients with schizophrenia, 193 of their siblings, and 47 normal comparison subjects. Relative risk (l) was estimated by using cutoff scores that were one, two, and three standard deviations below the mean sensitivity index value (d cent) of the normal comparison group in both Continuous Performance Test conditions.


RESULTS
Patients but not their siblings performed worse than the normal comparison subjects in both conditions. Fifty percent of the patients, 24% of their siblings, and 18% of the normal comparison subjects scored one standard deviation below the mean score of the comparison group for the more difficult distraction version of the Continuous Performance Test. The patients with Continuous Performance Test scores one standard deviation below the mean score of the comparison group had a total of 97 siblings. Compared with the comparison group, this subgroup of siblings had significantly lower Continuous Performance Test scores. Relative risk was also significantly higher for the siblings of patients whose scores were one standard deviation (l=2. 1) and two standard deviations (l=3.3) below the mean of comparison subjects. Attempts to assess ascertainment bias suggest that this may be an underestimate.


CONCLUSIONS
Poor performance on the Continuous Performance Test appears to be familial and, possibly, genetic. Relative risk estimates were in the moderate range. Given the ease of administering the Continuous Performance Test, the use of impaired attention as an intermediate phenotype could increase the power of genetic studies of schizophrenia.
NIMH Nueorscience Research Center at St. Elizabeth's Hospital, Washington, DC, USA. eganm@intra.nimh.nih.gov
M F
MF
Egan
T E
TE
Goldberg
T
T
Gscheidle
M
M
Weirich
L B
LB
Bigelow
D R
DR
Weinberger
D000328:Adult; D001288:Attention; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D015331:Cohort Studies; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007360:Intelligence / Q000235:genetics; D008297:Male; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010641:Phenotype; D015995:Prevalence; D012306:Risk; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*; D012680:Sensitivity and Specificity