Abstract:In recent years， the incidence of depression has been continuously increasing in China. The prevention and treatment of depression has been elevated to the national strategic level. Establishing a multicenter and standardized large-scale prospective cohort study for depression can provide a comprehensively understanding of the pathogenesis and the disease outcomes under different intervention modes， and develop objective indicators system that can guide clinical practice. Therefore， the scientific and technological innovation 2030- prospective clinical cohort study of depression has launched， which is of great significance to the precision medicine research of depression in China. The authors combed the risks and research key points in the research and summarized the quality control measures of the cohort study from the aspects of team construction and personnel responsibilities， research objects， clinical data， multi-dimensional data， biological samples， follow-up， data management， and comprehensive quality control measures.

Abstract:Objective To explore the difference of cognitive impairment in patients with different subtypes of depressive disorder， and analyze the correlation between the cognitive function and brain-derived neurotrophic factor （BDNF） and pro-BDNF in patients with different subtypes of depression. Methods A total of 151 patients with first-episode major depressive disorder （MDD） admitted to the First Hospital of Shanxi Medical University from July 2020 to December 2021 and 40 healthy volunteers ［health control （HC） group］ from the same period were selected as the research objects. According to subtype classification criteria， the first episode MDD patients were divided into anxiety/somatization depression （ASD） group （n=78）， melancholy/under powered depression （MPD） group （n=53） and Atypia depression （ATD） group （n=20）. The scores of 17-item Hamilton Depression Scale （HAMD-17）， Repeatable Battery for the Assessment of Neuropsychological Status （RBANS）， BDNF and pro-BDNF were compared among the 4 groups. Spearman rank correlation was used to analyze the correlation between RBANS scores and BDNF and pro-BDNF in ASD， MPD and ATD groups， respectively. Results The length of schooling in ASD and MPD groups was lower than that in HC group ［（12.49± 4.05）years、（13.19±3.21）years vs（14.85±2.65）years］， and the differences was statistically significant （P ＜ 0.05）. The total scores of HAMD-17 in ASD， MPD and ATD groups were higher than that in HC group ［（21.88±3.79）、（19.87±3.22）、（18.60±2.35） vs（2.03±2.36）］， and the differences was statistically significant （P＜ 0.05）. The total scores of HAMD-17 in MPD and ATD groups were lower than that in ASD group， and the differences was statistically significant （P＜ 0.05）. The concentration of BDNF in ASD， MPD and ATD groups was higher than that in control group ［0.5（0.3，8.5）pg/ml、0.6（0.3，39.9）pg/ml、18.8（0.5，61.1）pg/ml vs 0.3 （0.2，0.5）pg/ml］， and the differences was statistically significant （P ＜ 0.05）. The RBANS scale scores and immediate memory， verbal function， attention， and delayed memory factor scores of the four study groups were significantly different（P＜ 0.05）. There was a negative correlation between BDNF and immediate memory factor in ASD group （r=-0.238， P＜ 0.05）. There was a positive correlation between pro-BDNF and visual span factor in MPD group （r=0.314， P ＜ 0.05）. Conclusions The cognitive function and BDNF level of patients with different subtypes of depressive disorder are different from that of healthy controls， and the cognitive function impairment of patients with different subtypes of depressive disorder is correlated with BDNF and pro-BDNF to some extent.

Abstract:Objective To discuss the differences in local spontaneous brain activity among patients with depressive disorder， major depressive episode with mixed feature （MMF）， bipolar disorder with mixed feature （BMF） and bipolar disorder （BD） by amplitude of low-frequency fluctuation. Methods From June to December 2021， resting state functional magnetic resonance imaging data and general information were collected from 20 patients with depression， 15 patients with MMF， 20 patients with BMF， and 25 patients with bipolar disorder who met DSM-5 diagnostic criteria and attended the outpatient clinic of Beijing Anding Hospital， Capital Medical University. 40 healthy people matched with each group in terms of gender and age were recruited as healthy controls during the same period. After image data preprocessing， individual ALFF maps were calculated， and differences in local spontaneous brain activity were explored using one-way ANOVA and post hoc tests. Results The results of one-way ANOVA show that patients with depressive disorder， MMF， BMF， and BD exhibited significant difference of ALFF in the left inferior temporal gyrus ［cluster size k=372， P ＜ 0.001， Family Wise Error （FWE） corrected］， left raphe nuclei （k=271，P ＜ 0.001， FWE corrected）， right anterior cingulum （k=193， P＜ 0.001， FWE corrected）， right middle temporal gyrus （k=149， P＜ 0.001， FWE corrected）， right superior media frontal gyrus （k=117， P＜ 0.001， FWE corrected）， right cerebellum crus （k=68， P=0.009， FWE corrected）， right inferior temporal gyrus （k=63， P=0.014， FWE corrected）， and left middle temporal （k=49， P=0.048， FWE corrected）. The post hoc test results showed that the ALFF values of the left inferior temporal gyrus in patients with bipolar disorder and BMF were higher than those in patients with depression， while the ALFF values of the right cerebellum in patients with MMF， bipolar disorder and BMF were lower than those in patients with depression， and the differences were statistically significant （P＜ 0.01）. The left raphe nuclei ALFF value of BMF patients was lower than that of MMF and depression patients （P＜0.05）. Conclusions In patients with affective disorder spectrum， local spontaneous brain activity in frontal lobe， temporal lobe， cerebellum， raphe nuclei and other brain regions is abnormal， but in BMF patients， compared with MMF patients， local spontaneous brain activity in raphe nuclei is weak.

Abstract:Objective To screen hub genes and potential therapeutic agents for major depressive disorder （MDD） by bioinformatics methods. Methods The GSE98793 and GSE76826 datasets in the GEO database were used as the data source. Data analysis， differential expression gene （DEG） screening and enrichment analysis were carried out using online tools and R soft. STRING database was used to analyze proteinprotein interaction network， and Cytoscape was used to screen hub genes. Receiver operating characteristic （ROC） curve was used to evaluate the diagnostic value， and Connectivity Map database was used to predict small molecule drugs for severe MDD. Results A total of 5 hub genes （TLR2， CD28， IL7R， IRF4， MAPK14） were screened out. The ROC curve results showed that the area under the ROC curve of the 5 hub genes in the GSE98793 and GSE76826 datasets ranges from 0.616 to 0.804. It was predicted that UBP-302， ketanserin， CS- 1657， androstenol， taurocholic acid， a total of 5 small molecule drugs， may have potential value in improving the symptoms of patients with major depressive disorder. Conclusions TLR2， CD28， IL7R， IRF4， MAPK14 may be key genes in the pathogenesis of MDD patients. The 5 small molecule compounds UBP-302， ketanserin， CS-1657， androstenol， and taurocholic-acid may have a certain effect on improving depressive symptoms and can provide ideas for subsequent drug research.

Abstract:Depression seriously affects the daily work and life of patients， and leads to a huge financial and medical burden. Non-invasive brain stimulation （NIBS）， as a non-invasive neuromodulation method， has been widely used in the non-drug treatment of depression. Precision medicine is a new trend in biomedical oriented depression diagnosis and treatment. After nearly two decades of rapid development， NIBS is now based on rich data from neuroimaging studies， which allows it to develop personalized interventions from multiple dimensions within a precision medicine framework， such as finding more precise treatment parameter algorithms， focus on brain state goals to expand frequency parameter space and search for evidence of patients' biological subtypes to achieve the purpose of improving patient efficacy. This paper reviews the current NIBS efforts and progress towards precision medicine in the field of depression treatment.

Abstract:Major depressive disorder （MDD） is a highly heterogeneous disease. Antidepressants are the preferred treatment for MDD， among which selective serotonin reuptake inhibitors （SSRI） and serotonin and norepinephrine reuptake inhibitors （SNRI） are commonly used antidepressants in clinical practice. However， currently clinical medication treatment mainly relies on the clinical experience of doctors， with significant individual differences in efficacy and a lack of objective efficacy evaluation indicators. This article reviews the magnetic resonance neuroimaging features related to the efficacy of SSRI and SNRI， aiming to find the common or specific neuroimaging features that can predict or evaluate the efficacy of SSRI and SNRI antidepressants， so as to provide reference for the individualized and precise treatment， expecting to improve antidepressant effect.

Abstract:Objective To explore the abnormal social decision-making behavior of adolescent depression patients， so as to reflect the problem of its social function. Methods From September 2020 to February 2021， a total of 49 adolescent patients who were treated in outpatient or inpatient department of Beijing Anding Hospital and 25 healthy adolescents in community were selected as research subjects. Hamilton Depression Scale-17 （HAMD-17）， the Patient Health Questionnaire-9 （PHQ-9） and Generalized Anxiety Disorder （GAD-7） were applied to assess patients' depression and anxiety symptoms. The repeated measurement ANOVA was used to compare the difference in the acceptance rate and reaction time of the ultimatum game paradigm scheme between the two groups of subjects， and the post task questionnaire was used to assess the cognitive difference between the two groups of subjects on the fairness of the scheme after the task was completed. Results The HAMD-17， PHQ-9， and GAD-7 scores of patients in the depression group were higher than those in the healthy control group， with statistically significant differences （P＜ 0.05）. There was no statistically significant difference in acceptance rates between the two groups of subjects （P＞ 0.05）. In terms of acceptance rate， the main effect of fairness is statistically significant （F=201.760， P＜ 0.01， partial η2 =0.737）， and there is an interaction between fairness and proposer categories （F=8.791， P ＜ 0.01， partial η2 =0.109）. There was no statistically significant difference in reaction time between the two groups of subjects （P ＞ 0.05）. In terms of reaction time， the main effect of scheme fairness is statistically significant （F=42.755， P ＜ 0.01， partial η2 =0.373）， and the main effect of the scheme proposer is statistically significant （F=5.333， P ＜ 0.05， partial η2 =0.069）. There is an interaction between fairness and proposers （F=8.946， P＜ 0.01， partial η2 =0.111）. There is no statistically significant difference in the total score of the post task questionnaire between the two groups of subjects （P＞ 0.05）. However， the score of question 1 in the post-task questionnaire of the depression group was 6.4 （1.0， 10.0） points， which was lower than the 8.0 （2.0， 10.0） points of the healthy control group， with a statistically significant difference （Z=-3.235， P＜ 0.01）. Conclusions There is no significant abnormality in the social decision-making behavior of adolescent depression patients， which is related to their understanding of fairness in allocation plans.

Abstract:Objective To analyze the clinical characteristics of acute ischemic stroke （AIS） in nonvalvular atrial fibrillation （NVAF） patients with prior anticoagulant therapy. Methods Data of NVAF patients with AIS hospitalized in the Department of Neurology， Xuanwu Hospital of Capital Medical University from January 2016 to December 2021 in the observational study （NCT04080830） was retrospectively analyzed. Patients were divided into the non-anticoagulant， adequate anticoagulant and insufficient anticoagulant groups according to anticoagulant status before onset. The clinical characteristics were compared among the three groups. Results A total of 749 AIS patients with NVAF were recruited， including 661 in non-anticoagulant group， 33 in adequate anticoagulant group and 55 in insufficient anticoagulant group. The rates of massive infarction and the scores of National Institute of Health Stroke Scale （NIHSS） at admission and discharge of the adequate anticoagulant group were lower than those of the non-anticoagulant group［15.2%（5/33）vs 34.2% （226/666），4.00（1.00，7.50）vs 8.00（3.00，15.00），2.00（0，5.00）vs 4.00（1.00，12.00）］. The proportion of patients with scores of Modified Rankin Scale （mRS） ≤ 2 at discharge in the adequate anticoagulant group were higher than that in the non-anticoagulant group ［66.7%（22/33）vs 44.0%（226/666）］. The differences were statistically significant （all P ＜ 0.05）. The proportion of intravenous thrombolysis in the adequate anticoagulant group and the insufficient anticoagulant group was lower than that in the non-anticoagulant group［3.0%（1/33） and 3.6% （2/55）vs 5.6% （37/666）］， and the difference was statistically significant （P ＜ 0.01）. Compared with the nonanticoagulant group and the insufficient anticoagulant group， patients in the adequate anticoagulant group had higher rates of cardioembolic/ large-artery AIS ［42.4%（14/33）vs 21.8%（144/666） and 16.4%（9/55）， P＜ 0.01］. Conclusions Adequate anticoagulant therapy in NVAF patients might be associated with milder ischemic stroke severity and better outcomes at discharge. The mechanism of competitive large artery atherosclerosis induced AIS may be one of the reasons why adequate anticoagulant treatment fails to effectively prevent and control AIS risk in NVAF patients.

Abstract:Objective To explore the changes in discrimination and related attitudes of hospitalized patients with schizophrenia patients from 1999 to 2021. Methods Using the convenience sampling method， 136 patients with remission stage schizophrenia from August to September in 1999 and 146 patients from August to September in 2021 were selected to investigate their discrimination status and related attitudes using mental disability discrimination attitudes and experiences questionnaire. Results In 2021， the scores of the discrimination against patients with mental disorders and their families subscale in mental disability discrimination attitudes and experiences questionnaire were （62.67±11.70） among patients with schizophrenia， lower than （66.88±7.61） in 1999， and the difference was statistically significant （t=3.361， P＜ 0.01）. In 1999， the percentage of patients who answered "agree" or "strongly agree" to "social discrimination against people with mental illness has decreased significantly in the last 20 years" " social discrimination often leads families to keep the mentally ill a secret" and " the unit （school） is fair to the mentally ill” was 63.97%（87/136）、63.97%（87/136）、 36.02%（49/136）， respectively， which is lower than that of 71.91%（105/146）、78.08%（114/146）、63.70%（93/146） in 2021， with statistically significant differences （Z=5.644， 2.541 and 4.617； P ＜ 0.05）. Conclusions The situation of discrimination against schizophrenia patients has improved compared to 20 years ago， but discrimination still has a significant impact on the psychological and social life of schizophrenia patients. There is still a long way to go to improve the problem of discrimination against mental disorders.

Abstract:At present， the common prevalence of game addiction and depressive symptoms in the adolescent population is constantly increasing， but the correlation between the two psychological problems and the risk factors for their comorbidity are not clear. Therefore， this article reviews the research progress on comorbidities and depressive symptoms of adolescent game addiction in recent years. Adolescents with game addiction are at a higher risk of developing depressive symptoms， which can also affect emotional regulation and social function. The influencing factors of the comorbidity of game addiction and depressive symptoms in adolescent mainly include self-escape， parenting style and peer relationship， which are related to loneliness， self-control and peer attachment respectively. Family intervention is the most feasible and effective coping strategy at present. It is suggested to flexibly combine interactive and restrictive intervention methods according to the actual situation. The curriculum construction of parents for adolescents with game addiction and depressive symptoms should focus on the construction of parent-child relationship， positive attention to adolescents' emotions and school life. Future studies can further clarify the relationship between adolescent game addiction and depressive episodes in the context of online classrooms， and explore the therapeutic effect of family intervention through long-term follow-up.

Abstract:Parkinson disease （PD） is a common neurodegenerative disease， of which pathogenesis remains unclear. An increasing number of studies have indicated mitochondrial dysfunction may play a key role in the development of PD. Numerous mitochondrial-associated risk genes for PD have been identified. This article reviews the progress of mitochondrial-associated genes and the treatment of mitochondrial dysfunction in PD， aiming to deepen the understanding of the role of mitochondria in PD.

Abstract:Central nervous system lesions or injuries are often associated with advanced brain dysfunction， and some patients have poor efficacy in monotherapy. Therefore， there is an urgent need for new treatment methods to assist drug therapy. As a new type of neural rehabilitation technology， high-definition transcranial direct current stimulation regulates the neural activity of the cerebral cortex by acting on specific brain regions with low-intensity current through specially designed high-precision electrodes. At present， highdefinition transcranial direct current stimulation has shown varying degrees of improvement in post-stroke aphasia， disturbance of consciousness， depression， cognitive impairment after epilepsy and other advanced brain dysfunction diseases. This article takes the principle and mechanism of action as the starting point， and combines domestic and foreign research results to summarize the research on high-precision transcranial direct current stimulation and its clinical application in advanced brain dysfunction， aiming to provide a basis for future development