Clinical Risk Factors And Proteomic Mechanisms Of Post-stroke Depression

Objective To investigate the risk factors and possible mechanisms in patients with acute post-stroke depression(PSD),in order to provide theoretical basis for clinical prediction of PSD and early intervention in the future.Method(1)The first part of the study: We prospectively analyzed the patients diagnosed with acute cerebral infarction in the 940 th Hospital of the Chinese People’s Liberation Army Joint Logistic Support Force during January 2021 to August 2022,the Hamilton Depression Scale(HAMD)was used to assess the emotional state of each patient within 1 week after admission.According to the scale score,objects were divided into PSD group and post-stroke non-depression group,and PSD patients were further divided into subgroups according to their severity.We compared clinical data between groups to identify independent risk factors for PSD and its severity.(2)The second part of the study: After the PSD patients in Part I were selected,we used The Pittsburgh Sleep Quality Index(PSQI)divided the population into four groups: Very Good(VG),Fairy Good(FG),Fairy Bad(FB),and Very Bad(VB).By comparing clinical data between groups,we identified independent risk factors for sleep quality in patients with PSD.(3)The third part of the study: Patients with PSD in the second part were selected,and patients who visited the hospital during the same period with non-organic nervous system lesions were selected as the control group.All the people were divided into mild,moderate,severe/extremely severe PSD(due to the small number of people in the two groups,they were combined into one group to reduce bias)and the control group,a total of 4 groups.We randomly selected blood samples of patients in each group from the blood bank,5 cases in each group,and conducted sample detection by proteomic method to analyze the expression and interaction of differential proteins between groups.Combined with bioinformatics enrichment analysis,we searched for possible molecular biological functions and pathways,so as to explore the pathogenesis of PSD involved in differential proteins.Results(1)137 patients were included in the first part of the study,including 82 patients with PSD and 55 patients with non-depression patients after stroke;The incidence of PSD was about 60%(82/137).There were statistically significant differences in Gender,TOAST classification,pulse/heart rate,pre-stroke NIHSS scores,HAMA scores,grade of PSQI,history of smoking and drinking,HGB level,basal ganglia,brain stem and centrum semiovale acute infarction between groups((49)<0.05);Correlation analysis showed that gender,pulse/heart rate,pre-onset NIHSS score,HAMA grade,PSQI grade,acute stage of basal gangland infarction were positively correlated with PSD,while TOAST score,smoking history,drinking history,HGB level,acute stage of brainstem infarction were negatively correlated with PSD.The Logistic regression analysis showed that post-stroke anxiety and pre-stroke sleep quality were independent risk factors for PSD.Comparing on PSD each subgroup,We found that there were statistically significant differences in gender,height,weight,MRS score after stroke,grade of PSQI,HAMA scores and ADL grading,history of smoking and drinking,history of clopidogrel treatment,oral medications,HCT,CK,Scr,acute thalamic and occipital lobe infarction between groups((49)<0.05);Correlation analysis showed that gender,PSQI grade,HAMA grade,ADL grade,oral hypoglycemic agents,acute infarction of thalamus and occipital cortex were positively correlated with the severity of PSD,while smoking history,HCT and creatinine were negatively correlated with the severity of PSD.The logistic regression analysis showed that pre-stroke sleep quality,oral hypoglycemic agents and serum creatinine value is an independent risk factor for PSD severity.(2)In the second part of the study,82 patients with PSD were included,including 10 patients in VG group,37 patients in FG group,30 patients in FB group and 5 patients in VB group.Comparing the clinical data between the groups,there were statistically significant differences between the groups in baseline data,such as days from onset to visit,systolic blood pressure,alcohol consumption history,hypertension history and PSD severity((49)<0.05);The difference indexes of fibrinogen,blood Na,uric acid and triglyceride in laboratory test were statistically significant between groups((49)<0.05);No statistically significant difference was found in imaging data((49)>0.05).Correlation analysis showed that the severity of PSD was positively correlated with sleep quality,and the history of alcohol consumption and hypertension was negatively correlated with pre-stroke sleep quality of PSD patients.History of alcohol consumption and hypertension were independent risk factors for pre-stroke sleep quality in patients with PSD.(3)In the third part of the study,20 blood samples were included,15 in the PSD group,5in each subgroup,and 5 in the healthy control group.The differential protein screening between the PSD group and the healthy control group showed that there were 8 up-regulated proteins and 26 down-regulated proteins.Further analysis of the subgroups and the healthy control group showed that there were 17 up-regulated proteins and 44 down-regulated proteins.The co-down-regulated proteins were APOA2,SERPINA5,LYZ,ALB and PRSS1,and all appeared in the down-regulated proteins of PSD group and healthy control group.The PPI protein interaction map showed that ALB of the five co-down-regulated proteins was located in the center of the protein interaction network.GO enrichment analysis suggested that down-regulated proteins were involved in the regulation of inflammatory response,and KEGG pathway analysis revealed that the complement system was a co-down-regulated pathway.Conclusion(1)Pre-stroke sleep quality was an independent risk factor for PSD and its severity.(2)The sleep quality of PSD patients could be independently affected by drinking history and hypertension history;(3)Albumin may be involved in the pathogenesis of PSD through the complement system,and inflammation plays an important role.