The Characteristics Of Executive Function Impairment In Drug-na?ve Patients With Bipolar Depression And The Correlation With White Matter Integrity

Background and Objective: Cognitive impairment is one of the core symptoms of bipolar depression(BDP).Even a part of euthymic patients may suffer from cognitive impairment which affects their quality of life and social function continuously.But the BDP patients’ cognitive impairment,especially the executive impairment,is underestimated in clinical practice.Additionally,the relevant neural mechanism of the executive impairment is unclear.Therefore,we used several approved neuropsychological tests to explore the characteristics of executive impairment in BDP patients.The diffusion tensor imaging(DTI)was also applied to explore the changes of brain white matter associated with executive impairment so that to provide some evidence about the neural mechanisms of BDP patients’ executive impairment.Methods: This was an assessor-blind,cross-sectional study.Drug-na?ve Patients with BDP,matched UDP and healthy controls(HC)were recruited(46 cases in each group).The severity of symptoms in patients were assessed.All subjects’ executive function was evaluated by Stroop color-word test(CWT)and Wisconsin Card Sorting Test(WCST).The DTI data were acquired by Siemens 3.0 Tesla magnetic resonance(MRI)scanning.Part one was the analyses about the characteristics of BDP patients’ executive impairment.The CWT and WCST were compared between groups.The correlation between executive function and clinical characteristics were identified using partial correlation analysis.Part two was the exploration of the changes of brain white matter associated with BDP patients’ executive impairment.DTI data were preprocessed by FSL 5.0 toolkit.Statistical analysis was conducted by TBSS.The comparisons of whole-brain and ROI were all performed.The correlation between executive function and FA/MD/AD/RD values were identified using partial correlation analysis.Results: Part one: There was no significant difference between BDP patients and UDP patients in executive function.Compared with HCs,The CWT’s number of correct was lower in BDP patients(P=0.039).In UDP patients,the CWT’s number of correct was lower,number of missing was higher,PCLR was smaller(P<0.017).the number of missing of CWT in BD-A was higher(t=2.172,P=0.033).The number of categories completed(CC)and failure to maintain categories(FM)of WCST in BD-NA were different from those in HC(P<0.05).In BDP group,CWT’s reaction time was related to the duration of disease(r=0.380,P=0.012),WCST-CC was influenced by age of onset and duration of disease(r=0.401,P=0.008;r=-0.333,P=0.029),PCLR was correlated to age of onset positively and duration of current depressive episode negatively(r=0.349,P=0.022;r=-0.309,P=0.044),total score of WCST was related to age of onset negatively.In UDP group,the CWT’s number of error was related to the duration of disease,WCST’s PPR and PPE were related to HAM-A total score(r=-0.373,P=0.014;r=0.347,P=0.023),FM was positively related to HAM-D(r=0.317,P=0.038).Part two: 26 BDP patients,33 UDP patients and 39 HCs were included in this part.There was no significant difference in the white matter structure of BDP,UDP and HC in the whole-brain level,and the uncorrected results of FA/MD/AD/RD were mainly in unclassified brain area.The ROI data analyses showed the FA of the left cingulum(cingulate gyrus)in BDP patients was higher than HCs(t=2.069,P=0.041),the MD of the right uncinate fasciculus(UF)in UDP patients was lower than HCs(t=-2.026,P=0.046).In BDP group,the age of onset was related to the bilateral cingulum(cingulate gyrus)and the left inferior fronto-occipital fasciculus(IFOF),the duration of disease was correlated with the right cingulum(cingulate gyrus)and the right cingulum(hippocampus),HAM-A total score was related to the middle cerebellar peduncle(MCP)and splenium of corpus callosum(sCC)and the left IFOF(P<0.05).In UDP group,the age of onset was related to the right cingulum(cingulate gyrus)and bilateral UF and right IFOF,HAM-A was related to the AD of left cingulum(cingulate gyrus)negatively(r=-0.392,P=0.024).The BDP patients’ CWT performance was correlated with left UF,the WCST was related to the bilateral IFOF and UF(P<0.05).The UDP patients’ CWT performance was related to bilateral cingulum(cingulate gyrus)and the left UF,the sCC and the left cingulum(cingulate gyrus)and bilateral UF(P<0.05).There was no difference in white matter microstructure in subjects with executive impairment and the subjects without executive impairment.Conclusions: Our results suggested there was executive impairment in drug-na?ve BDP patients.BDP-A performed worse in stress-related tasks,and BDP-NA performed worse in non-stress-related tasks.No difference was detected in executive function between drug-na?ve BDP patients and UDP patients.The executive function of drug-na?ve BDP patient was influenced by the duration of current depressive episode and age of onset and duration of disease,however those in UDP patients was affected by duration of disease and anxiety symptom.No significant white matter abnormalities in the whole-brain analysis were observed in drug-na?ve BDP patients.The potential abnormal brain regions in BDP patients were more than those in UDP patients,and there were differences in the potential white matter structural changes related to executive function in patients with BDP and UDP.