Cognitive Deficits Endophenotype And The Methylation Status Of MB-COMT CpG Island In Schizophrenia And Sibings

ObjectTo explore whether schizophrenic patients and their biological siblings have deficits in cognition, and could these cognitive deficits be regarded as endophenotype in genetic research to reduce the genetic heterogeneity of subjects. Moreover, we aimed at preliminary exploration on the role of epigenetic modification of MB-COMT namely CpG island methylation in peripheral blood in schizophrenia and the cognitive deficits endophenotype.MethodsWe applied a set of cognition tests including general intelligence, digital span, instant and time delayed visual memory, instant and time delayed verbal logical memory, STROOP color interference test, CPT, WCST and verbal fluency on 32 schizophrenic patients, 32 their biological siblings and 30 normal controls. In the quantitative study of DNA methylation on CpG island in MB-COMT from peripheral blood, the gold standard method, Bisulfite Genomic Sequencing, was used in this study.Results1. Patients with schizophrenia showed a wide range of cognitive deficits including working memory, executive function, continuous attention, general intelligence and thinking speed when demographic matched with siblings and normal controls.2. Siblings of schizophrenia showed deficits only in instant verbal memory and delayed verbal memory which were significantly different from normal controls. Meanwhile, these measures in sibling group were significantly different from patient group, whichindicating that the cognitive deficits in siblings are milder than in patients.3. The CpG island in MB-COMT from peripheral blood were generally hypomethylated in schizophrenic patients, siblings and normal controls. Verbal logic memory deficits, the endophenotype found in our study, were not correlated with the methylation status of CpG island in MB-COMT from peripheral blood.Conclusions1. Patients with schizophrenia showed a wide range of cognitive deficits, including continuous attention, executive function, working memory, thinking speed and general intelligence.2. Siblings of schizophrenia showed deficits only in instant verbal memory and delayed verbal memory representing the deficits in coding process, while not in saving and retrieval process. Verbal logic memory could be measured as endophenotype of schizophrenia in genetic research to reduce the heterogeneity of subjects.3. The CpG island in MB-COMT from peripheral blood were generally hypomethylated in schizophrenic patients, siblings and normal controls. The methylation level of CpG island in MB-COMT from peripheral blood may not involved in the cognitive deficits endophenotype in schizophrenia.