| Objective: As a mood stabilizer, valproate had been widely used to treatment of bipolar disorder in clinical practice. At present, valproate had neuroprotective effects, neurotrophic role in the promotion of neurite growth, antiapoptotic effect etc. It was considered that possibly can help prevent or reverse pathological changes in the brain of bipolar disorder. In this study, we applied methods of neuropsychological to assess characteristic of cognitive impairment in the patients with bipolar disorder, and explored valproate sodium for the treatment of cognitive impairment in manic patients with bipolar disorders.Methods: According to the selection criteria, manic patients with bipolar disorder were enrolled from the inpatient Institute of Mental Health, the First Hospital of Hebei Medical University between December 2008 to December 2009. The patients were randomly divided into valproate combined with quetiapine group (combined group) and quetiapine monotherapy group (monotherapy group), and healthy subjects as normal controls. Written informed consent was obtaind from all subjects after complete description of the study. Dose of Sodium valproate was fiexible, it was 0.4-1.8g / d, the dose of quetiapine of two groups of patients were gradually increased to 800mg / d in 1 week. According to the state of illness, we adjusted dose of quetiapine . Two groups of patients were assessed cognitive function in 1 week. Respectively we typically used Wisconsin Card Sorting Test (WCST) to measured executive function, Hopkin Verbal Learning Test-Revised (HVLT-R)to measured memory and Continuous Performance Test (CPT) to measured sustained attention. Two groups of patients were assessed cognitive function at post-treatment(6 weeks) again and obtained the data. At pre- and post-treatment(6 weeks), Two groups of patients were assessed clinical characteristics with Young Mania Rating Scale (YMRS) and Clinical Global Impression of Severity of Illness(CGI-SI). At 2,4,6 weeks, we monitored adverse reactions with Treatment Emergent Symptom Scale. SPSS 16.0 statistical software was used to carry on statistics processing, t-tests, chi-square test was used to comparison of two groups, Turkey of analysis of variance was used to intercomparison among three groups.Results: The combined group, monotherapy group and the normal controls were 33 people, 31 people and 30 people. All three groups were matched on gender ratio, age, level of education and other general information (P>0.05). At pre-teatment, difference of the clinical variables include duration of illness, age of onset, numbers of hospitalization, numbers of episode, scores of the YMRS, CGI-SI were not significant between two patient groups (P>0.05). After 6 weeks, average dose of quetiapine used combined group was 645.5±185.56 mg /d, average dose of quetiapine used monotherapy group was 687.1±138.42 mg /d, there was not significant difference between the two patient groups (P>0.05). Maximum dosage of sodium valproate was 1.8 g / d, minimum dosage was 0.6 g / d, average dose was 1.02±0.35 g / d. The first, compared to normal controls, performance of the six indicators of WCST, HVLT-R, CPT of two patient groups were poorer, the difference was significant (P<0.01). Intercomparison of three groups showed that there was not significant difference between the two patient groups (P>0.05). After 6 weeks, the measurement scores of WCST and HVLT-R of the two patient group were still worse than normal controls, the difference was a statistically significance (P<0.01). Comparison of normal control and two patient groups, the measurement scores of CPT were not significant difference (P>0.05). Intercomparison of three groups showed that assessed scores of WCST, HVLT-R and CPT were not significant difference between two patient groups (P>0.05). Regardless of monotherapy group or combined group, scores of WCST, HVLT-R were poorer than normal controls. Three groups did not differ significantly on the scores of CPT (P>0.05). Self-control of pre- and post-treatment showed measurement scores of HVLT-R of the two patient groups were not significant difference (P>0.05). But, scores of CPT were significantly improved post-treatment, the difference was significant (P<0.01). Measurement scores of WCST showed that increaseing number of categories completed and reducing numbers of responses errors in the two patient groups, the difference was statistically significant(P<0.05 or P<0.01). numbers of perseverative errors had not significant difference (P>0.05). Compared to pre-treatment, numbers of perseverative responses of monotherapy group were not significant change (P>0.05). Unlike monotherapy group, numbers of perseverative responses of combined group were reduced, the difference was significant (P <0.05).After 6 weeks, difference for the scores of YMRS and CGI-SI were not significant between two patient groups (P> 0.05). Compared to pre-treatment, scores of YMRS and CGI-SI of the two patients groups were decreased at post -treatment, there were significant differences. The two patients groups had the mild adverse reaction such as drowsiness, dry mouth, constipation, weight gain. Some have moderate sleepiness, weight gain and constipation. Individual patients of combined group had nausea, anorexia, sweating, hair loss. Two groups of patients were able to tolerate adverse reactions, after appropriate treatment, the further treatment was not influenced.At pre- and post-treatment, blood and urine routine, ECG, liver function and other tests showed not obvious abnormality.Conclusion: 1. Patients with bipolar disorder in manic state existed cognitive impairment, such as frontal executive function, learning and memory ability, attention, etal. 2. When the disease was improved, attention impairment in bipolar disorder was gradually returned to normal levels, but the impairment of executive function and verbal learning continued to exist, it was not improved when clinical symptoms were alleviated. Results suggested that some type of cognitive impairment of bipolar disorder might be trait markers, such as executive function, verbal memory and so on, they had nothing to do with the clinical status. But some types may be state and illness-related, such as attention. When the clinical symptoms was improved, the impairment could be restored normal levels. 3. Valproate could improve operation scores of numbers of perseverative responses of WCST in mania patients with bipolar disorder. |
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