Objectives1Applying questionnaires survey, we are aiming to evaluate incidence of depressive status among undergraduates as well as the correlations between personality traits, life events and depressive status, subjective assement quality of life, further to elucidate the susceptible personality traits and potential stressor related to depressive status and key factors impacting quality of life assessment..2We conducted electroacupuncture, psychology and combination of electro-acupuncture and psychology treatments to undergraduates under depressive status to illuminate the effectiveness and necessarity of early interventions. Moreover, we analyzed the differentcs among interventions to figure out the advantages of different treatments, further to offer suggestions for the optimization of superior depressive status treatment strategy.3Applying circulating microRNA high throughput sequencing, we are aiming to explore bio-markers, related to depressive status and its pathogenesis. Meanwhile, we are aiming to shed light on the potential mechanism of early intervention based on analysis on differences in microRNA profiles pre-and post-interventions.Methods1Applying classic cluster sampling, undergraduates from school of medicine, pharmacy, Chinese medicine, administration and nursing, Inner Mongolia Medical University were recruited for questionnaire survey. Center for Epidemiologic Studies-Depression scale (CES-D) was used to measure depressive status (CES-D≥16was defined as depressive while CES-D<16as non-depressive), NEO-Five Factor Inventory (NEO-FFI, consisted of five dimensions:neuroticism, extraversion, openness to experience, agreeableness and conscientiousness) was applied to measure personality traits, Life Events Scale (LES) was used to evaluate the incidence of life events and their effects, and World Health Organization Quality Of Life Scale Abbreviated Version (WHOQOL-BREF) was employed to measure the subjective assessment of quality of life. Independent t-test were used to compare the differences of NEO-FFI, WHOQOL-BREF and LES scores, futhrermore, we applied AMOS to construct Structural Equation Model (SEM) to analyze the correlations and mediation effects of all variables2Individuals with CES-D≥16were futher evaluated with Hamilton Depression Rating Scale-17(HDRS-17) and Mini International Neuropsychiatric Interview (M.I.N.I.). Based on the inclusion criteria (7≤HDRS-17<1and excluding psychiatric disorders) and exclusion criteria,33subjects were recruited:33subjects were included for Full Analysis Set (FAS), with6in Electroacupuncture (EA) group,10in Cognitive Behavior Therapy (CBT) group and6in combination EA and CBT group and11in group;29subjects were included for Per Protocol Set (PPS), with5in EA group,9in CBT group,5in combination group and11in group. Intention To Treat (ITT) analysis and Per Protocol (PP) analysis were employed to evaluate the primary outcome measures (clinical response rate based on rate of HDRS-17score changes, clinical remission defined as an endpoint HDRS-17score<7and HDRS-17score after intervention). Meanwhile differences of HDRS-17factor scores, CES-D scores and WHOQOL-BREF scores were compared via Analysis of Variances (ANOVA).36samples from depressvie subjects prior to intervention,3samples form depressvie subjects after intervention and8samples from normal subjects were obtained. Total circulating RNA was extacted from serum sample via Trizol method. Then microRNA library were built and microRNA expression were profiled with Illumina high throughput sequencing. Target predction analysis, GO Enrichment analysis and KEGG pathway analysis were applied to predict potential targeting gene and protein of microRNA expressed differentially between depressive and normal subjects as well as those between prior to and after treatmentResults12262valid questionnaires were withdrawn for analysis. The mean score of CES-D was10.64±7.95. General quality of life score, overall health score, physical, psychological, social relationship and environment domain scores in WHOQOL-BREF were3.62±0.84,3.67±0.86,69.02±12.96,65.44±13.90,67.35±17.45,60.12±13.86respectively. Compared with non-depressive group, general quality of life score, overall health score, physical health, psychological, social relationship and environment domain scores in WHOQOL-BREF, extraversion, openness to experience, agreeableness, conscientiousness scores in NEO-FFI of depressive group were significantly lower (P<0.01), while positive and negative life events scores in LES and neuroticism scores in NEO-FFI were remarkably higher (P<0.01).. The results of SEM demonstrated neuroticism, extraversion, openness to experience, agreeableness and conscientiousness as well as life events factors including university life, failure in college entrance examination, being in or broken up relationships are predive to depressive status (P<0.01), standardized regression weights are0.4926,-0.2257,-0.0725,-0.0581,0.0588,0.0556,0.0373respectively. Extraversion, conscientiousness, neuroticism as well as life events factors including university life, economic factors and personal achievement can predict quality of life assessment, standardized regression weight are0.2642,0.2229,-0.1983,-0.0796,-0.0455,0.0043respectivly. Depressvie status is predictive to quality of life assessment with standardized regression weight-0.207. Direct effects of personality traits, life events on quality of life assessment are higher than indirect effects mediated by depressive status. Total effects exerted by personality traits including extraversion, neuroticism and conscientiousness outweigh those by life events.2Early intervention research2.1ITT and PP analysis demonstrated that primary outcome measures in intervention group were significantly superior to those in non-intervention group.(P<0.01)2.2ITT and PP analysis demonstrated that primary outcome measures in EA group, CBT group and combination group were superior to those in non-intervention group, no statistically significant differences were found among EA, CBT and combination group.2.3Comparisons of HDRS-17factor scores showed that post-treatment anxiety/somatization, insomnia, retardation and cognition scores in EA group, CBT group and combination group were remarkably lower than pre-treatment scores(P<0.01), while no significant difference was found between pre-and post-treatment in depressive control group(P>0.05). Post-treatment anxiety/somatization score in combination group was lower than those in EA group and CBT group (P<0.01); post-treatment insomnia score in EA group was siginificantly lower than those in combination group and CBT group (P<0.01); post-treatment retardation score was lower in CBT and combination group compared with those in EA group (P<0.01). No significant differences was found in cognition score among EA, CBT and combination group (P>0.05). No great difference was found between pre-and post-treatment in body weight scores in four groups (P>0.05).2.4CES-D score in EA group, CBT group and combination group were lower than that in non-intervention group (P<0.01), no statistically significant differences was found among EA, CBT and combination group (P>0.05).2.5Post-treatment general quality of life score, overall health score, physical health, psychological and social relationship domain scores from WHOQOL-BREF in EA, CBT and combination group improved compared with pre-treatment scores (P<0.01), while no significant difference was found between pre-and post-treatment in depressive control group(P>0.05). No significant differences was found in post-treatment general quality of life score, overall health score, physical health, psychological and social relationship domain scores among EA, CBT and combination group (P>0.05). No great difference was found between pre-and post-treatment in general quality of life and environmental domain scores in four groups.390types of known microRNA expressed differentially between depressive group and normal group, among which82were upregulated and8were downregulated; while87types of novel microRNA expressed differentially between depressive group and normal group, among which64were upregulated and23were downregulated.173types of known microRNA expressed differentially between pre-treatment group and post-treatment group, among which85were upregulated and88were downregulated; while63types of novel microRNA expressed differentially between pre-treatment group and post-treatment group, among which19were upregulated and44were downregulated. GO enrichment and KEGG pathway analysis displayed that differentially expressed microRNA were predicted to be correlated to pathways including apoptosis, circardian rhythm, neurotrophins, mitogen-activated protein kinase (MAPK), inflammatory response signal factor TGF-beta and vascular endothelial grow factor(VEGF).Conclusions1The undergraduates in the current study showed favorable emotional status and relatively high quality of life assessment. Life events and personality traits contributs to the occunce of depressive status which furher leads to decline in quality of life assessment. Main stressors including academic stress, changes in life regularity, misunderstood by others, econominc problems warrant great attention. Personality traits play a crutial role in depressive status occurrence and quality of life assessement, indicating that fostering favorable personaties may be of significant importance to maintain undergraduates’ mental health and life satisfaction.2Early intervention could alleviate depressive symptoms and improve subjective assessment of quality of life. Different intervention target different symptoms, specifically, EA could improve somatic symptoms and insomnia while CBT favors mitigating cognition and mood dysfunction. The combination treatment targent both physical and psychological symptoms and can substantially improve overall health, thus might be an ideal stratugy for depressive status intervention.3The occurence of depressive status might be closely correlated to alterated levels of microRNA related to depression pathology, and changes in several signal pathways mediated by certain microRNAs were predicted to be the underlying mechanism of early intervention which is related to modulations of neuro-endocrine-immune network. However, these predictions of microRNA as bio-markers and their roles in ealy internvention warrant further investigation via verification tests. |