| Background:the major depressive disorder is common disorder, with significant and persistent low mood. Point prevalence is1.9%-4.5%and lifetime prevalence of3.3%-6.87%. The survey in1990by WHO shows the major depression disease burden accounted for6.2%of the burden with neuropsychiatric disease, and it continues to increase until2020. Depression brought huge economic burden, even severe cases can affect family stability and social order. In the past it was thought that the major depression is Paroxysmal disease, and the patients in remission are normal completely, but recent studies showed there were residual symptoms even in remission, such as depression, inability to concentrate and diminished ability to adapt to social and other issues. So impact of depression on the individual is not limited to stage of attack.With the increasingly attention to cognitive dysfunction in patient with major depression, it was found that cognitive dysfunction still exisits in pateients with remission, even if the core symptoms of depression disapeared. The residual cognitive dysfunction may lead patient’s bad feels about themselves and diminished ability to adapt to the society, and the patients with residual cognitive dysfunction are more likely to recurrence than patients without it. Neuropsychological deficits in depression are not simply a consequence of age, poor motivation, inattention or response bias. The cognitive dysfunction does not appear to be epiphenomena of depressive disorder, but rather an intrinsic expression of the brain changes in depressive illness. It has been suggested that cognitive dysfunction in MDD patients might be independent, not secondary to depressive symptoms, and has different biological basis from depression. CAMP (cyclic adenosine monophosphate) response element binding (CREB) is an important nuclear protein, and a member of DNA transcription factor family. Research has increasingly focused on the role of the (CREB) protein in learning and memory, particularly its role in cognitive disorders and neurodegeneration, such as Huntington’s disease, Alzheimer’s disease, Rubinstein-Taybi syndrome and Coffin-Lowry syndrome. The cognitive dysfunction of patients with major depressive disorder (MDD), which is widely recognized, is not completely in accordance with depressive severity, and the dysfunction persists upon clinical remission in some patients. However, few studies have focused on the role of CREB on cognitive function in patients with MDD. This study aimed to investigate the influence of CREB1polymorphism on cognitive function in patients with MDD.Brain derived neurotrophic factor (BDNF) is a member of the nerve growth factor family. It has important roles in the neuron survival, growth and differentiation, and can affect neuronal plasticity and it has protective effect on neurons regeneration. BDNF is mainly distributed in hippocampus and cortex in brain, and hippocampus and cortex is important brain region in learning and memory, executive function, attention, cognitive function, so it suggests that BDNF may be related to cognition. In recent years, the animal studies have been carried out to research the role of BDNF on cognitive function, and disease studies have been carried out, such as Alzheimer’s disease, Parkinson’s disease and schizophrenia. However, the studies conclusions about it are not consistent and there is less study about the relationship of BDNF and cognitive function in patients with depression. Therefore this study is to explore the relationship between serum levels of BDNF and BDNF gene polymorphism with cognitive function respectively in patients with depression.Method:(1) The current study comprised74patients with MDD and35healthy individuals.17-item Hamilton rating scale for depression (17-HAMD), Hamilton rating scale for anxiety (HAMA), Self-rating depression scale (SDS) and Self-rating anxiety scale (SAS) were used to evaluate the level of depression and anxiety. The Stroop Neuropsychological Screening Test (SNST), Trail Making Test (TMT), Verbal Fluency Test (VFT), logical memory and visual reproduction were used to evaluate cognitive function. Data analysis are done by SPSS13.0software in windows and the analysis method include t test, Mann-Whitney U test, pearson correlation analysis, spearman correlation analysis, partial correlation analysis and multiple linear regression.(2) The current study comprised111patients with MDD. The severity of depression was measured using the17-item Hamilton Depression Rating Scale, and cognitive function was assessed using the Stroop Neuropsychological Screening Test, verbal fluency test, and tests of immediate logical memory and visual reproduction. All subjects were genotyped with regard to CREB1polymorphisms (rs10932201, rs2551645, rs2254137, rs6740584and rs2551640). Data analysis are done by SPSS13.0software in windows and the analysis method include t test, Mann-Whitney U test, x2test, pearson correlation analysis, spearman correlation analysis and multiple linear regression.(3) The current study comprised113patients with MDD and35healthy individuals.17-HAMD was used to evaluate the level of depression. SNST, VFT, logical memory test and visual reproduction test were used to evaluate cognitive function. Using enzyme-linked immunelsorbent assay (ELISA) serum BDNF levels were detected in patient group and control group. All patients were genotyped with regard to BDNF polymorphisms (rs6265). Data analysis are done by SPSS13.0software in windows and the analysis methods include t test, Mann-Whitney U test, x2test, pearson correlation analysis and spearman correlation analysis.Results:(1) controlled years old and education, the time in Stroop-C task, the correct number in Stroop-CW task, the time in trail making A task, the time, wrongs and the times pen leaving paper in trail making B task, the rights in verbal fluency test and the performance in logical memory show different significantly between diseases and health (p<0.05) and the performance in visual reproduction show different (p=0.056).(2) The correct number in Stroop-CW task have significant negative correlation with SDS and SAS scores respectively (p<0.05), and repeats number in word fluency test have significant negative correlation with onset age(p<0.05), and has significant positive correlation with disease duration (p<0.05). And visual regeneration test scores has positive corrletaion with onest age (p=0.061) and has negative correlation with disease duration (p=0.067).(3) For the verbal fluency test, the results showed significant differences for all single nucleotide polymorphism genotypic groups. For the Stroop color-word task, a significant difference was found only for rs6740584. No significant differences were found for the Stroop color task, the immediate logical memory test or the visual reproduction test.(4) Patients have lower serum BDNF concentration significantly than the control group (p<0.05). The serum BDNF concentration have negative correlation with17-HAMD scores in patient group (p=0.058), and with error number (p=0.090).(5) In recessive model, the correct number in Stroop-C task is lower in AG/GG group than in the AA group (p=0.087). In dominant model there is no significant different in any neuropsychological tests scores.Conclusion:(1) The patients with major depression have poor performance than healthy individuals in executive function, attention and memory function. Attention function is related with the severity in anxiety and depression in a certain degree, and the executive function and memory are related with onset age and duration of disease in a certain degree.(2) There was an effect of CREB1polymorphism on selective attention and retrieval of long-term memory, but not on immediate memory.(3) The patients with major depression have low serum BDNF concentration than healty individuals, and serum BDNF levels have correlation with the severity of depressive symptoms in a certain degree. And no correlation was found between cognitive function and serum BDNF levels.(4) No correlation was found between BDNF gene polymorphism and cognitive dysfunction in major depression. |
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