A Comparative Study On Cognitive Function And Association Analysis Of The 5-HTTLPR And COMT Gene Polymorphism In Patients With OCD And Comorbid OCD With BD

OBJECTIVE: Both obsessive-compulsive disorder (OCD) and bipolar disorder (BD) are common mental disorders, associated with notably genetic predisposition and cognitive impairment, and often comorbid with each other. In present study, the performances in cognitive function of patients with OCD and OCD comorbid with BD were compared to those of healthy control subjects in order to discover the differences among the three groups. By molecular-genetic technique, the association between the polymorphisms of the 5-HTTLPR and COMT genes in patients with OCD and OCD comorbid with BD were studied.METHODS: Patients Group: A group of patients (n = 81) met the diagnosis criteria of OCD and another group of patients (n = 74) met the diagnosis criteria of both OCD and bipolar disorder of DSM-IV was enrolled into the research. A general investigating form(including the demographic information and clinical characteristics), Yale-Brown Obsessive-Compulsive Scale(Y-BOCS) and its obsessive-compulsive symptom checklist, Hamilton Depression Scale(HAMD), Hamilton Anxiety Scale(HAMA),and Bech-Rafaelsen Mania Scale(BRMS)were completed at the enrollment of the subjects, and the scores were recorded. Moreover, Wisconsin Card Sorting Test(WCST), Trail-Making Test A & B,and Block design subtest of Wechsler intelligence Scale for children( WISC: BD) were employed to assess the subjects'cognitive function.Normal controls:112 healthy people were drawn from a general population as the comparative subjects who were mentally normal without either a history of lifetime mental disorders or psychoactive substances dependence, or a family history of any gross mental disorders. They matched the patients grossly for age and educational levels. SCL-90 was used to exclude those with mood and/or obsessive-compulsive symptom. The Y-BOCS (Chinese version) was also employed to rule out those with a total score over 6. Subjects with severe medical conditions, physical disability, achromatopsia, color weakness and noncompliance were excluded. All of them undergone a set of neuropsychological tests listed above after they enrolled.All of the subjects, including patients and controls, were Chinese with Han nationality and right handedness. At their enrollment 5ml venous blood sample was drawn to extract DNA for the purpose of molecular genetic analysis.Some clinical features (including course of illness, family history, the age of onset, substances abuse and self-injury and suicidal behavior) between the patients of OCD and OCD comorbid with BD were compared. All of the test performances were compared between the three groups. In addition to neuropsychological tests, the 5-HTTLPR and COMT gene from all individuals were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Frequencies of genotype and alleles were analyzed in all of the three groups.RESULTS: 1) The comparison of course, family history, age of onset, substances abuse and self-injury and suicidal behavior between two patients'groups revealed that the course of OCD prolonged significantly in the patients of OCD comorbid BD.2) Compared with normal controls, the patients with OCD showed significantly worse performances on Trails B-A, A stroke counts and B stroke counts. Patients with OCD comorbid with BD performed significantly poorer on many measures, including TMT-A, TMT-B,TMT B-A, WCST total categories, persevative and total errors, and total scores of the WISC block design, than control subjects. However, except errors of TMT-A,TMT-Band the nonperseverative errors of WSCT did not differ significantly between OCD group and OCD comorbid BD group, the other measures were significantly different between the two groups.3) A)The genotype of 5-HTTLPR gene were consisted with Hardy-Weinberg equilibrium in three groups (χ2=2.723,df=1, p=0.098,χ2=2.668,df=1, p=0.102 andχ2=0.001,df=1, p=0.980); and the genotype of COMT gene were also consistent with Hardy-Weinberg equilibrium among the groups (χ2=0.001,df=1, p=0.971,χ2=0.207,df=1, p=0.649 andχ2=2.118, df=1, p=0.146); B) The distribution of genotypes or alleles of 5-HTTLPR gene were not significantly different between the three groups, neither the COMT gene(p>0.05);and C) Divided by gender, there were no significant differences of genotypes or alleles distribution in 5-HTTLPR and MAOA genes between the three groups.CONCLUSION: 1) Comorbidity of BD seems to prolong the course of OCD. 2) Though patients with OCD and those with OCD and BD comorbidity have impairment in cognitive function, the impairment in comorbid ones are more sever, suggesting comorbid BD has additional impact on their cognitive function. 3) The distribution patterns of genotypes and frequencies of alleles of both 5-HTTLRP and COMT do not associated with OCD or OCD comorbid with BD. 4) Distribution patterns and frequencies are not associated with OCD or OCD comorbid with BD, no matter of male or female.