Relationship Between Cognitive Impairments And Duration Of Illness In Euthymic Patients With Bipolar Disorder

BackgroundGenetic epidemiological studies have shown that bipolar disorder is highly heritable. There is not yet a breakthrough on the etiological studies until now, because of the heterogeneity of clinical symptoms. Endophynotypes maybe provides a new strategy to solve this problem. Lots of researches have shown that patients with bipolar disorder in acute period impair in cognitive function. There are many studies shown that attention, memory, processing speed and executive function are impaired in euthymic BD patients. Moreover, healthy relatives of BD patients also have impaired in such domains, which has been found in schizophrenia. These findings suggeste that these cognitive impairments be clinical independent rather than dependent. It is not clear that whether these dimensions'impairment of cognition are affected by the progress of the disease. Impaired domains of cognition which are independent with clinical state can provide trails for etiology of bipolar disorder, and which are dependent for clinical intervention.HypothesisThere may be two kinds of cognitive impairments in euthymic Bipolar Disorder: one is stable across the duration of illness, and the other is duration dependent.MethodsThe study uesed cross-sectional study and longitudinal study to explore the relationship between cognition impairment and duration of illness. Cross-sectional study included large sample of euthymic patients with Bipolar Disorder. After the first evaluation at least 1 year, 50 patients among the large sample received the same evaluation of cognitive function in euthymic period.Sample 1: for cross-sectional study224 euthymic patients with Bipolar I disorderwere recruited from the outpatients and inpatients of Guanzhou brian hospital from August 2006 to December 2010. All the patients fulfilled the bipolar I disorder criteria of DSM-IV(Diagnostic and Statistical Manual of Mental Disorders),and had been in remission for at least 3 months when recruited. Digtal symbol, trail making test (TMT) A and B, digital span, visual reproduction, Wisconsin Card Sorting Test (WCST), verbal fluency, Tower of Hanoi (TOH) were employed to assess cognitive function in memonry, attention, processing speed and executive function.1) Patient were divided into three groups: Group I(3 months≤duration of illness≤24 months) was 79 cases; Group II(24 months< duration of illness≤60 months) 58 cases; and group III(duration of illness>60 months): 87 cases. Chi-square analysis and ANOVA were used to compare diffenences of sex, age and years of education among groups.2) Spearman correlation and partial correlation were used to analyze the correlation between cognitive function and duration of illness. Sample 2: longitudinal study 50 cases from SAMPLE 1, who had been in remission for at least 3 months prior to the second evaluation. The cognitve evalution was the same as that of sample 1. Paired-Samples T test and nonparametric test for two related sample were employed to test the cognitive function between two evaluations. ResultsCross-sectional study:1) Repeat of verbal flunency, errors of TMT-B ,among three groups were significantly different (P<0.05), which was better in Group I than that in Group II (P<0.05).2) Only errors of TMT-B is associated with the duration of illness (p<0.05). The other 23 markers were not related with duration of illness.Longitudinal study:1) Memory: No significant differences were shown between two evaluations in forward of digital span and visual reproduction(p<0.05). Backward and total score of digital span in the second evaluation were significantly better than the first time (p<0.05).2) Attention and processing speed: No signigicant differences were found between the two evaluations in Digital Symbol, uptakes of TMT-A, errors of TMT-A(p<0.05). Time of TMT-A, time of TMT-B, errors of TMT-B were significantly better in the second evluation than that in the first evaluation(p<0.05). In patients who did not relaped, digital symbol, time of TMT-A, time of TMT-B, uptakes of TMT-B were significantly better in the second time than that in the first time.3) Exacutive function: In total group of follow-up patients, types of WCST, total errors of WCST, total score of verbal fluency, plan time of TOH were significantly better in the second evaluation than that in the first time. None relapse subgroup performanced significantly better in the second evaluation in types of WCST, total errors of WCST, total score of verbal fluency, total score of TOH, missions of TOH(P<0.05). Plan time of TOH taked by the relapse subgroup in the second time was significantly less than in the first time(P<0.05).Conclusion1)Memorya) Visual reproduction, digital span forward are stable and independent with duration of illness in euthymic BD patients. They may be endophetypes of BD;b) Digital span backward is independent with duration of illness in the cross- sectional study, and in none relapse subgroup in the longitude study. This index may be influenced by the duration of euthymia. Further study is needed.2)Attention and processing speed:a) Errors of TMT-A is stable and independent with duration of illness in euthymic BD patients, which may be endophetype of BD;b) Corss-sectional study indicated that perfomance on digital symbol, time of TMT-A, uptakes of TMT-A, time of TMT-B, errors of TMT-B, uptakes of TMT-B are independent with the duration of illness. But longital study showed that they may all increase if there are no relapse. c) The relationship between errors of TMT-B and duration of illness need further exploration.3)Executive functiona) Cross-sectional study indicated that, types of WCST, total errors of WCST, perseverative errors of WCST, total score of verbal fluency, total score of TOH, missions of TOH, executive time of TOH are independent with duration of illness, they are stable. Longitudinal study indicated that they may be increased if the patients'condition are stable.b) Cross-sectional study indicated that patients with longer duration of illness performanced worse on repeat of verbal fluency than the shorter ones. Longitudinal study indicated that this index is stable.c) Plan time of TOH has no relationship with duration of illness in the cross-sectional study. Longitudinal study showed that relapse subgroup used less time to plan in TOH missions than the first evaluation, while the none relapse subgroup used the same.Above all,most index reflected processing speed, attention, exacutive function of euthymic BD patients are not strong stable, they may be influenced by episode or the time of euthymic.