Cognitive Function Of Bipolar DisorderⅠPatients And Health First-degree-relatives, And Association Between Cognitive Function And Rs947267 Polymorphism Of G72 Gene

BackgroundThe cause of bipolar disorder (BD) is not clear. Heredity is very important in the etiology of BD,but the study on molecular genetics of BD has much difficulties because of the clinical heterogeneity of BD. Endophenotype may resolve questions of clinical heterogeneity of BD and help much more to explore predisposing genes of BD. Cognitive function may be one of the endophenotypes of BD. Now researches indicated that attention, memory and executive function were impaired in BD patients, even in euthymic BD patients. But the results of congnitive impairment and their charicteristics were not confirmed. The study on cognitive function of healthy first-degree-relatives (FDRs) of BD was still few. Results showed the healthy FDRs of BD may have impairment in cognitive function, but the specific charicteristics of their cognitive impairment and its relationship with the cognitive impairment of BD patients were still confirmed. G72 gene might associate with BD. But the researches on the relationship between G72 gene and cognitive function in BD were rarely reported,and few research on the relationship between G72 gene and relatives of BD was reported.ObjectiveTo investigate the impairment of attention, memory and executive function and their influencing factors in patients with bipolarⅠdisorder (BD-Ⅰ); To investigate the impairment of attention, memory and executive function in healthy FDRs of BD-Ⅰ, and to find the endophenotype of BD from the common impairment indexes between the patients and FDRs; To explore the relationship between rs947267 polymophism of G72 gene and BD-Ⅰor probable cognitive endophenotype indexes respectively.MethodsThrough collecting families, 242 euthymic BD-Ⅰpatients, which accorded with Hamilton rating scale for depression (HAMD) <7, Young mania rating scale (YMRS) <6 and euthymic period≥3 months, 231 healthy FDRs of BD-Ⅰ, including 185 parents and 46 siblings, and 162 normal controls were included in the study. Digital symbol, trail making test (TMT) A and B, digital span, visual reproduction, verbal fluency, Wisconsin card sorting test (WSCT) and tower of Hanoi (TOH) were used to assess cognitive function such as attention, memory and executive function. Differences of cognitive function among patient groups,relative groups and controls were analized by linear mixed model method, and influencing factors of cognitive function in patients were studied by partial correlation. The differences of cognitive function among patients, siblings and normal controls were studied, which were matched by gender, year and year of education to control confounding factors better in this small specimen. To test the genotypes of rs947267 polymophism of G72 gene in 202 patients, 231 relatives and 103 normal controls. Case-control based association analysis was used in patients and normal controls, and haplotype-based haplotype relative risk (HHRR) used in 65 nuclear families, and pedigree disequilibrium test (PDT) used in patients, parents and siblings. The relationship between probable cognitve endophenotype indexes of BD-Ⅰas quantitative genetic characters and rs947267 polymophism was analized.Results(1) Compared with normal controls, BD-Ⅰpatients were significantly impaired in digital symbol, time of TMT-A and TMT-B, all indexes of digital span, visual reproduction, total scores of verbal fluency, all indexes of WSCT and TOH (P<0.05).(2) Compared with normal controls, FDRs of BD-Ⅰwere significantly impaired in digital symbol, time of TMT-A and TMT-B, all indexes of digital span, visual reproduction, total scores of verbal fluency, all indexes of WSCT and TOH (P<0.05). This result was accord with that of comparing with patients and normal controls. Compared with matched normal controls, siblings were significantly impaired in time of TMT-A, error of TMT-A, all indexes of digital span, total scores of verbal fluency, mission scores of TOH and executive time of TOH (P<0.05).(3) Compared with matched siblings, patients were significantly impaired in time of TMT-B, visual reproduction, persistent errors of WSCT and executive time of TOH (P<0.05). While compared with FDRs and parents respectively, the results also showed patients were impaired in categories of WSCT and executive time of TOH (P<0.05).(4) The achievement of categories of WSCT and executive time of TOH had a tendency to increase among total patients, FDRs and normal controls, or among total patients, parents and normal controls, or among matched patients, siblings and matched normal controls. Differences among them were significant (P<0.05) except difference of categories of WSCT between mathced patients and siblings, also between matched siblings and normal controls.(5) Compared with nonpsychotic bipolar disorder (NPBD) patients, psychotic bipolar disorder (PBD) patients were significantly impaired in digital symbol, total scores of TOH and mission scores of TOH (P<0.05).(6) In BD-Ⅰpatients, YMRS significantly correlated with total scores of TOH, mission scores of TOH respectively, duration of illness with all indexes of TMT-B respectively, and age at onset with TMT-B uptake and persistent errors of WSCT respectively. But the correlations were weak (|r|≤0.211). Length of euthymia significantly correlated with none of the cognitive functional indexes (P>0.05).(7) No significant association was showed between rs947267 polymorphism of G72 gene and BD-Ⅰby using case-control, HHRR and PTD (P>0.05).(8) No significant association was showed between rs947267 polymorphism of G72 gene and quantitative characters of digital symbol, time of TMT-A and TMT-B, all indexes of digital span, visual reproduction, categories of WSCT and executive time of TOH by using case-control, HHRR and PTD (P>0.05).Conclusion(1) BD-Ⅰpatients had cognitive impairments in attention, memory and executive function, which was independent with clinical characteristics, such as length of euthymia. Cognitive impairment of PBD patients might be severer than that of NPBD patients.(2) There were some common impairment in attention, memory and executive function between BD-Ⅰpatients and their healthy FDRs, which could be endophenotypes of BD-Ⅰ, such as time of TMT-A, all indexes of digital span, total socres of verbal fluency, categories of WSCT and executive time of TOH.(3) Categories of WSCT and executive time of TOH might be the endophenotype indexes of BD-Ⅰmostly.(4) No association was showed between rs947267 polymorphism of G72 gene and BD-Ⅰ.(5) No association was showed between rs947267 polymorphism of G72 gene and indexes of attention, memory and executive function.