| Background:Major depression disorder is one of the common chronic mental disorders,but its pathogenesis is not clear so far.At present,the main methods for the treatment of depression are drug therapy and psychotherapy.Drug therapy is effective for most patients,but it is easy to rebound and have side effects,and a small number of patients with depression are ineffective for drug treatment;cognitive and behavioral intervention is effective,but individual differences lead to increased difficulty of operation,which is not suitable for large population.In recent years,it has been found that the therapeutic effect of exercise on depression is obvious,but the study of exercise dose response in patients with depression is still unclear.Therefore,for college students with depression with large individual differences and wide distribution,physical activity(PA)intervention may be a more effective way to alleviate depression.PA refers to any physical activity caused by skeletal muscle contraction that can increase the energy consumption of the body.It can quantitatively and qualitatively evaluate the improvement of depression.Although the study found that physical exercise can improve the symptoms of depression,and the occurrence of depression is related to the lack of physical activity,the mechanism of PA improving depression is not clear.With the development of sensor technology and mobile communication technology,the use of a variety of physiological electrical signals to explore the psychological and physiological characteristics of mental disorders has become a research hotspot.Electroencephalogram(EEG)and electrocardiogram(ECG)physiological signals can reflect the information characteristics of psychological and physiological state in different degrees.According to the clinical characteristics of depressive symptoms,depression patients have organic pathological changes in physiological function due to long-term emotional depression,in which the disorder of bioelectric signals is an obvious sign.Therefore,it provides a research method for exploring the physiological and psychological mechanism of physical activity to improve the symptoms of patients with depression.Metabonomics is a method to analyze the related metabolic mechanism of human body from the point of view of molecular biology.By detecting the changes of small molecular metabolites and screening the changes of differential metabolites and related metabolic pathways,this method can reveal the metabolic mechanism of depression and the improvement mechanism of metabolic pathway induced by PA intervention.Research Purpose:Therefore,this study applied high physical activity to the selected depressed college students as an improvement method,explored the effect and neurophysiological mechanism of physical activity in improving depressed college students from multiple perspectives,and provided theoretical basis for using physical activity as an effective means to improve depression in college students.Research methods:1.According to the Baker Depression scale(BDI)and the self-rating Depression scale(SDS),from the freshmen and sophomores of non-sports majors in our university,college students with moderate or above symptoms of depression(screening criteria for moderate depression:BDI score≥15,and SDS score≥50)need to go through the diagnosis of physical diseases and development in the university hospital of our university.After excluding other diseases and abnormal physical development and other interference factors,determined as the experimental subjects of this project;In addition,all the subjects need to sign the informed consent form,and the whole experiment program needs to be approved and supervised by the Special Committee of Science and Ethics of our university;the subjects are randomly divided into two groups:depression group(D),physical activity intervention group(D+PA),according to the requirements of human study statistics,each group has no less than 30 people;at the same time,the same number of healthy students of the same age were selected as normal control group(N).2.Except that all the students in each group participated in the physical education class once a week(required by the college physical education syllabus),the students in the D+PA group were required to receive extracurricular physical activity intervention twice a week,with a total intervention time of 90 min,for 18 weeks,except holidays.The intervention of physical activity is organized and publicized in the form of "Sunshine Sports Association";the content of physical activity intervention is selected as follows:interesting collective events(small field football,air volleyball,campus orienteering,yoga,sports games,etc.);exercise intensity is medium intensity,that is,the heart rate is controlled at 120,150bpm/min;.The implementers of physical activity intervention are graduate students majoring in physical education and training after unified training.in the intervention of students’ physical activities,the implementers are emphasized on entertaining and humanized teaching and communication,and are not allowed to be indifferent and scold the experimental subjects.in order to avoid the interference of emotional conflict.3.The subjects’ total physical activity was monitored by wearing a physical activity level(GT3,ActiGraph,USA).Wearing mode:left wrist;wearing time:GT3 wearing time is 1 week,9 weeks,18 weeks,that is,each semester needs to wear 3 weeks,physical activity data extraction and analysis using Actilife software 6.1 analysis software,collection frequency:0.25-2.5 Hz,collection interval:5s;The identification of medium intensity physical activity and high intensity physical activity is according to Friedson(Freedson)standard,the medium intensity collection interval is 2690 to 6167 counts/min;and more than 6167 counts/min is the high intensity collection area,the time of medium and high intensity physical activity is measured in min,and the "bout" parameter is adopted,and the duration of 10 min is set as the effective time.In addition,the BDI and SDS scores of students in each group were tested at the end of the 1 st,9th and 18th weekend of the semester,so as to monitor the changes of students’ depression symptoms.3.Firstbeat physical function monitor was used to detect the physical function of college students in each group for 24 hours.The R-R interval data are extracted and analyzed in time domain.Based on the fast Fourier transform,the time domain is converted into frequency domain,which is divided into high frequency power(HF,0.150.40 Hz)and low frequency power(LF,0.04-0.15 Hz)for frequency domain analysis.To explore the daily functional status of depressed college students and the characteristics of improvement after PA intervention.4.EEG signal acquisition method:The EEG and ERP signals of each group of students were collected by using the high-resolution EEG acquisition system of 32 conductive cap extended by the international 10mur20 system(Brain Vision Recorder;Neuroscan,USA).The acquisition date:one week before and the first week after the intervention,the collection should be completed within one week.Within 24 hours before collection,the subjects could not take drugs,caffeinated beverages,tobacco or alcohol,and could not have events such as high-intensity exercise and large mood swings;EEG acquisition conditions:the filter bandpass was 0.05 Hz,the sampling frequency was 1024 Hz/,the impedance between all electrodes and the scalp was less than 5 k,and the collection time was 8 min in sitting with eyes open and eyes closed.ERP signal acquisition method:acquisition instruments and conditions are the same as EEG;The target stimulation task is set up by psychological professional software EPrime 3,0(PST,USA).The novel Oddball paradigm is used to evaluate the cognitive function,that is,the central presentation stimulus of the black background,there are three stimuli,including the standard stimulus "number 2"(the presentation probability is 80%),the target stimulus "number 8"(the presentation probability is 10%),and the novel stimulus "bright picture"(the presentation probability is 10%).The presentation time of each stimulus was 600 ms.5.The urine samples of the subjects were collected,and the metabolites in the urine of group N and D before intervention and group D+PA after intervention were detected by liquid chromatography-mass spectrometry(LC-MS).After LC-MS detection,the mass spectrometry data were analyzed by multivariate pattern recognition using SIMCA software(V14,Umetrics AB,Umea,Sweden).Principal component analysis of the samples can generally reflect the overall differences among the samples and the degree of variation between the samples within the group.Using PCA and OPLS-PA multidimensional statistical processing,all compounds were screened for potential differential metabolites through the Kyoto Encyclopedia of Gene and Genome(KEGG)database.The contribution value of differential metabolites to this group(VIP),t-test probability p value,and the similarity degree(Similarity)of the corresponding substances to KEGG database were used as the screening indexes of differential metabolites,that is,VIP>1,p<0.05,and similarity>700.Finally,the selected differential metabolites were inputted into the MetPA database(http://www.metaboanalyst.ca),and the influence weights of the corresponding metabolic pathways were analyzed.The main metabolic pathways of depression college students were screened out according to the influence score>0.01 as the main criterion.And analyze the improvement mechanism of PA intervention on college students with depression.Research Results:1.Compared with those before intervention,the scores of SDS and BDI in D+PA group decreased significantly,while the scores of SDS and BDI in group D had no significant difference.2.The results of Go-nogo paradigm behavior data showed that the average reaction time in the Go task in the depression group was higher than that in the normal control group(p<0.001),the average correct rate of Go in the depression group was lower than that in the control group,the average correct rate of Go in the control group was higher than that in the control group,and the average reaction time without inhibition in the depression group was higher than that in the normal group(p<0.05).The ERP signals of response inhibition ability showed that the latencies of N2 and P3 were prolonged,the amplitudes of P3 decreased and the amplitudes of N2 increased(p<0.001),and the results of P300 of novel stimulation showed that the latencies of college students in depression group were significantly longer and the amplitudes were significantly lower than those in healthy groups(p<0.001).The resting EEG rhythm showed that the energy of delta band in the depressed college students was significantly lower than that in the healthy group(t=2.600,p=0.011)in,theta band(t=-3.974,p=0.0002),in alphal band(t=-3.828,p=0.0003),and in alpha2 band(t=-4.393,p=0.0003).There was no significant difference in the energy of theta2 band,but there was marginal significance in betal band(t=1.881,p=0.064).Compared with those before intervention,the energy in delta band in physical activity intervention group increased significantly(t=9.394,p<0.000),theta band(t=-2.486,p=0.019),and in alpha2 band(t=-8.317,p=0.000),while there was still marginal difference in beta1 band and extremely significant increase in beta2 band(t=10.839,p=0.000).3.The results of daily stress time,recovery time and heart rate variability(HRV)showed that compared with the healthy group,the stress time of depression group increased significantly(p<0.001),the recovery time decreased significantly,the time domain indexes SDNN and RMSSD decreased significantly,and the average heart rate increased significantly(p<0.001).The indexes of LF and HF in frequency domain decreased significantly(p<0.01).The results of correlation analysis between recovery time,pressure time and HRV index showed that recovery time was negatively correlated with pressure time and average heart rate,and positively correlated with HF,RMSSD and SDNN.The difference was significant or very significant.Pressure time was negatively correlated with SDNN.After 18 weeks of intervention,compared with the depression group,the time domain indexes SDNN and RMSSD in the high physical activity group were significantly higher,the average heart rate was significantly lower,and the frequency domain indexes LF and HF were significantly higher than those in the depression group.The correlation analysis of the difference of depression score before and after physical activity intervention and the difference before and after HRV showed that the correlation coefficients between RMSSD and HF in HRV index and BDI[(RMSSD:r 0.02-0.67);(HF r 0.03-0.74)]and SDS correlation coefficient[(RMSSD:r 0.008-0.63),(HF:r 0.01-0.79)]were statistically significant.4.15 differential metabolites were screened out in depression group,and 15 differential metabolites were identified between depression group and healthy control group.Among them,5 metabolites were positive ion pattern,including dihydrothymine,corticosterone,indole methanol,methyluridine and p-ethyl benzoic acid.In the negative ion mode,10 substances were identified:formic acid,glycine,ursodeoxycholic acid,3hydroxybenzoic acid,m-cresol,4-hydroxybenzene lactic acid,azaleic acid,vanillin,dimethylglycine,gentian acid and ethylene glycol.The above differential metabolites are related to the disorders of five metabolic pathways(coenzyme Q biosynthesis,glycineserine-threonine metabolism,tyrosine metabolism,pyrimidine metabolism and steroid metabolism).After the intervention of high physical activity,33 differential metabolites with significant changes were screened.Eighteen of them were screened under positive ion mode:phenylaniline-proline,histidine,acetyl histidine,4-aminobutyric acid,canine urinary quinolinic acid,3-hydroxysiphonic acid,trigonelline,acetylputrescine,dihydrothymine,p-aminobenzoic acid,proline,tyramine,dimethylglycine,aminophenol,glycyl,nicotinic acid,methyluridine and pyridoxamine.All showed a significant upward trend.However,15 differential metabolites were screened in the negative ion model,and their relative contents were compared with those before intervention,except for the significant increase of 4-hydroxyphenyl lactic acid.Methanolic acid,indoleacetic acid,xanthine,indoleol sulfate,xanthine nucleoside,phosphoric acid,m-cresol,dimethylglycine,creatinine,vanillin,octanedioic acid,methyl histidine and glutamine showed a significant decreasing trend.It mainly involves 8 metabolic pathways(coenzyme Q biosynthesis,tyrosine metabolism,pyrimidine metabolism,tryptophan metabolism,glutamate-alanine-aspartic acid metabolism,histidine metabolism,arginineproline metabolism and glutamine-glutamate metabolism).Conclusion:1.After 18 weeks of high-level physical activity intervention for female college students with depression,the symptoms of depression were significantly improved,2.Female college students with depression have impaired attention and response inhibition function,and 18-week high-level physical activity intervention can improve the function of central nervous system.3.Daily stress time is longer than recovery time may be the main cause of autonomic nervous dysfunction in college students with depression,physical activity can improve the sympathetic nerve,vagus nerve activity and central regulation of sinoatrial node in college students with depression.4.There are disorders in five metabolic pathways of coenzyme Q biosynthesis,glycine-serine-threonine metabolism,tyrosine metabolism,pyrimidine metabolism and steroid hormone biosynthesis in college students with depression.High level of physical activity improves three of the above five metabolic pathways in college students with depression:coenzyme Q biosynthesis,tyrosine metabolism and pyrimidine metabolism. |
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