首次发病未用药老年抑郁症患者脑白质完整性的弥散张量成像研究

Objective To explore the white matter integrity by using diffusion tensor imaging (DTI) in first-episode, medication-naive geriatric patients with major depressive disorder.Methods Fifteen first-episode, medication-naive depressive patients and fifteen healthy controls underwent DTI scan.Fractional anisotropy (FA) of white matter was compared between the two groups using voxel-based approach.Results Compared with healthy controls, geriatric depressive patients showed significantly lower FA in left anterior cingulate (cluster size = 106 voxels, t = 3.21 ), right anterior cingulate ( cluster size =60 voxels, t = 2.71 ), right subgenual cingulate ( cluster size = 63 voxels, t = 3.37 ) and left brainstem ( cluster size = 62 voxels, t = 3.25 ) ( level of significance was uncorrected single-tailed P ＜ 0.01, threshold of cluster size ＞ 50 voxels).Conclusion Decrease of white matter integrity in bilateral anterior cingulate and right subgenual cingulate are present in the early stage of geriatric depression.Lesions of neural pathways by way of these regions may be involved in the pathophysiology of geriatric depression.     

Effect of different therapies of Chinese medicine on the expressions of c-Fos and c-Jun proteins in hippocampus of rats with post-stroke depression

INTRODUCTION Post-stroke depression (PSD) is a common complication of stroke. PSD refers to the depressive symptoms of different severity occur af- ter stroke attack and last for more than two weeks[1], and its incidence in stroke patients is 12.0%- 60.1%…     

首次发病未用药老年抑郁症患者脑白质完整性的弥散张量成像研究

Objective To explore the white matter integrity by using diffusion tensor imaging (DTI) in first-episode, medication-naive geriatric patients with major depressive disorder.Methods Fifteen first-episode, medication-naive depressive patients and fifteen healthy controls underwent DTI scan.Fractional anisotropy (FA) of white matter was compared between the two groups using voxel-based approach.Results Compared with healthy controls, geriatric depressive patients showed significantly lower FA in left anterior cingulate (cluster size = 106 voxels, t = 3.21 ), right anterior cingulate ( cluster size =60 voxels, t = 2.71 ), right subgenual cingulate ( cluster size = 63 voxels, t = 3.37 ) and left brainstem ( cluster size = 62 voxels, t = 3.25 ) ( level of significance was uncorrected single-tailed P ＜ 0.01, threshold of cluster size ＞ 50 voxels).Conclusion Decrease of white matter integrity in bilateral anterior cingulate and right subgenual cingulate are present in the early stage of geriatric depression.Lesions of neural pathways by way of these regions may be involved in the pathophysiology of geriatric depression.     

抑郁症对海马及背外侧前额叶皮质神经元变与1HMRS表现及明尼苏达多项个性测量的相关性

Background and Purpose The present study was undertaken to elucidate neuro-structural and neuro-chemical characteristics of hippocampi and dorsolateral prefrontal cortex in patients with depressive disorder by using 1H-MRS and to study the association between 1H-MRS and Minnesota Mutiphasic Personality Inventory-2 in relation to the severity of the depression.. Methods Magnetic resonance imaging and 1H-MRS were performed on 33 patients with depressive disorder and age-18 and gender-matched healthy controls. Minnesota Mutiphasic Personality Inventory-2 test was performed on all depressive subjects and control subjects. Results Magnetic resonance imaging and 1H-MRS examinations showed widened sulcus and cisterns as well as the absence of abnormal signal in depressive patients. In addition, the N-acetyl aspartate/total creatine ratios in the bilateral hippocampi and dorsolateral prefrontal cortex were significantly lower in depressive patients than in the control subjects (P<0.01). In contrast, the choline-containing compounds/total creatine ratios in dorsolateral prefrontal cortex were remarkably higher in depressive patients than in the control subjects (Left: P<0.01, Right: P<0.01), the ratios of which were also significantly positively correlated with the depression scores of the patients assessed by Minnesota Mutiphasic Personality Inventory-2 scale (Right: r = 0.8787, Left: r = 0.9347). Conclusions 1H-MRS can be used to reveal reduced neuronal viability or function in the hippocampus and dorsolateral prefrontal cortex and altered membrane phospholipid metabolism in the dorsolateral prefrontal cortex in patients with depressive disorder. The 1H-MRS findings partially reflect the severity of the depressive disorder.     

The norepinephrine transporter gene is associated with the retardation symptoms of major depressive disorder in the Han Chinese population

The norepinephrine transporter plays an important role in the pathophysiology and pharmacological treatment of major depressive disorder.Consequently,the norepinephrine transporter gene is an attractive candidate in major depressive disorder research.In the present study,we evaluated the depression symptoms of subjects with major depressive disorder,who were all from the North of China and of Han Chinese origin,using the Hamilton Depression Scale.We examined the rela-tionship between two single nucleotide polymorphisms in the norepinephrine transporter,rs2242446 and rs5569,and the retardation symptoms of major depressive disorder using quantitative trait testing with the UNPHASED program.rs5569 was associated with depressed mood,and the GG genotype may be a risk factor for this;rs2242446 was associated with work and interest,and the TT genotype may be a risk factor for loss of interest.Our findings suggest that rs2242446 and rs5569 in the norepinephrine transporter gene are associated with the retardation symptoms of depression in the Han Chinese population.     

Structural Asymmetry of Dorsolateral Prefrontal Cortex Correlates with Depressive Symptoms: Evidence from Healthy Individuals and Patients with Major Depressive Disorder

In this study,we investigated the role of structural asymmetry of the dorsolateral prefrontal cortex(DLPFC) in the continuum of depression from healthy individuals to patients.Structural magnetic resonance imaging was performed in 70 patients with major depressive disorder(MDD),49 matched controls,and 349 healthy university students to calculate structural asymmetry indexes of the DLPFC.First-episode,treatment-naive MDD patients showed a relatively lower asymmetry index than healthy controls,and their asymmetry index was negatively correlated with the depressive symptoms.This abnormality was normalized by antidepressants in medicated MDD patients.Furthermore,the asymmetry index was negatively correlated with the depressive symptoms in university students;this was replicated at two time points in a subgroup of students,suggesting good test–retest reliability.Our findings are consistent with previous studiesthat support the imbalance hypothesis of MDD and suggest a potential structural basis underlying the functional asymmetry of the DLPFC in depression.In future,the structural index of the DLPFC may become a potential biomarker to evaluate individuals' risk for the onset of MDD.     

Altered serous levels of monoamine neurotransmitter metabolites in patients with refractory and non-refractory depression

The study examined plasma metabolite changes of monoamine neurotransmitters in patients with treatment-resistant depression (TRD) and non-TRD before and after therapy. All 30 TRD and 30 non-TRD patients met the diagnostic criteria for a depressive episode in accordance with the International Classification of Diseases, Tenth Revision. Before treatment, and at 4, 6, and 8 weeks after treatment, the plasma metabolite products of monoamine neurotransmitters in TRD group, including 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenyl ethylene glycol and homovanillic acid, were significantly lower than those in the non-TRD group. After two types of anti-depressive therapy with 5-serotonin and norepinephrine reuptake inhibitor, combined with psychotherapy, the Hamilton Depression Rating Scale scores were significantly reduced in both groups of patients, and the serous levels of 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenyl ethylene glycol were significantly increased. In contrast, the homovanillic acid level exhibited no significant change. The levels of plasma metabolite products of peripheral monoamine neurotransmitters in depressive patients may predict the degree of depression and the therapeutic effects of treatment.     

Efficacy of Lycium barbarum polysaccharide in adolescents with subthreshold depression: interim analysis of a randomized controlled study

Subthreshold depression is a highly prevalent condition in adolescents who are at high risk for developing major depressive disorder.In preclinical models of neurological and psychiatric diseases,Lycium barbarum polysaccharide(LBP)extracted from Goji berries had antidepressant effects including but not limited to anti-oxidative and anti-inflammatory properties.However,the effect of LBP on subthreshold depression is unclear.To investigate the clinical efficacy and safety of LBP for treating subthreshold depression in adolescents,we conducted a randomized,double-blind,placebo-controlled trial(RCT)with 29 adolescents with subthreshold depression recruited at The Fifth Affiliated Hospital of Guangzhou Medical University.The participants were randomly assigned to groups where they received either 300 mg LBP(LBP group,n=15,3 boys and 12 girls aged 15.13±2.17 years)or a placebo(placebo group,n=14,2 boys and 12 girls aged 15±1.71 years)for 6 successive weeks.Interim analyses revealed that the LBP group exhibited a greater change in Hamilton Depression Scale(HAMD-24)scores relative to the baseline and a higher remission rate(HAMD-24 total score≤7)at 6 weeks compared with the placebo group.Scores on the Beck Depression Inventory-II(BDI-II),Pittsburgh Sleep Quality Index(PSQI),Kessler Psychological Distress Scale(Kessler),and Screen for Child Anxiety-Related Emotional Disorders(SCARED)were similar between the LBP and placebo groups.No side effects related to the intervention were reported in either group.These results indicate that LBP administration reduced depressive symptoms in adolescents with subthreshold depression.Furthermore,LBP was well tolerated with no treatment-limiting adverse events.Clinical trials involving a larger sample size are needed to further confirm the anti-depressive effects of LBP in adolescents with subthreshold depression.This study was approved by the Medical Ethics Committee of the Fifth Affiliated Hospital of Guangzhou Medical University(Guangzhou,China;approval No.L2019-08)on April 4,2019 and was registered on ClinicalTrials.gov(identifier:NCT04032795)on July 25,2019.     

?In this issue (April 2016)?

正This issue begins with a systematic review and metaanalysis by Zheng and colleagues[1]about the use of a traditional Chinese medicine–Huperzine A(HupA)–as an adjunctive treatment for depression.The rationale for this treatment is that acetylcholinesterase(AChE)inhibitors may reduce the cognitive impairment that often accompanies depressive episodes and HupA is a powerful AChE inhibitor.After an exhaustive literature search in English language and Chinese     

Microglial NLRP3 inflammasome-mediated neuroinflammation and therapeutic strategies in depression

Previous studies have demonstrated a bidirectional relationship between inflammation and depression.Activation of the nucleotide-binding oligomerization domain,leucine-rich repeat,and NLR family pyrin domain-containing 3(NLRP3) inflammasomes is closely related to the pathogenesis of various neurological diseases.In patients with major depressive disorder,NLRP3 inflammasome levels are significantly elevated.Understanding the role that NLRP3 inflammasome-mediated neuroinflammation plays in the pat...     

Use of antipsychotics in the treatment of depressive disorders

Summary： There is a long history of using antipsychotic medications in the treatment of depressive disorders. Atypical antipsychotics, which have fewer side effects than traditional antipsychotics, have been used as monotherapy or adjunctively with antidepressants to treat depressive disorders with or without psychotic symptoms. The antidepressant effect of atypical ant-ipsychotics involves regulation of monoamine, glutamate, gamma-aminobutyric acid （GABA）, cortisol, and neurotrophic factors. To date, the United States Food and Drug Administration （USFDA） has approved aripiprazole and quetiapine slow-release tablets as adjunctive treatment for depressive disorders, and the combination of olanzapine and fluoxetine for the treatment of treatment- resistant depression. When using atypical ant-ipsychotics in the treatment of depressed patients, clinicians need to monitor patients for the emergence of adverse effects including extrapyramidal symptoms （EPS）, weight gain, and hyperglycemia.     

成纤维细胞生长因子2和成纤维细胞生长因子受体1蛋白在慢性应激抑郁大鼠海马中的表达

There is evidence that the expression of members of the fibroblast growth factor(FGF) protein family is altered in post-mortem brains of humans suffering from major depressive disorder.The present study examined whether the expression of fibroblast growth factor-2(FGF2) and fibroblast growth factor receptor-1(FGFR1) protein is altered following chronic stress in an animal model.Rats were exposed to 35 days of chronic unpredictable mild stress,and then tested using open-field and sucrose consumption tests.Compared with the control group,rats in the chronic stress group exhibited obvious depressive-like behaviors,including anhedonia,anxiety and decreased mobility.The results of western blot analysis and immunohistochemical analysis revealed a downregulation of the expression of FGF2 and FGFR1 in the hippocampus of rats,particularly in the CA1,CA3 and dentate gyrus.This decreased expression is in accord with the results of post-mortem studies in humans with major depressive disorder.These findings suggest that FGF2 and FGFR1 proteins participate in the pathophysiology of depressive-like behavior,and may play an important role in the mechanism of chronic stress-induced depression.     

拉莫三嗪治疗精神分裂症和双相抑郁及重性抑郁症耐受性与敏感性的文献分析

目的 分析拉莫三嗪在精神分裂症、双相抑郁和重性抑郁症急性期治疗中耐受性与敏感性.方法 选择符合急性期、随机双盲、安慰剂对照的关于拉莫三嗪治疗急性期精神分裂症、双相抑郁和重性抑郁症的临床试验进行分析;以不良事件引起治疗终止发生率为拉莫三嗪的耐受性指标,以皮疹和头痛为敏感性指标.分别计算拉莫三嗪(200 mg/d)事件发生率相对于安慰剂事件发生率增加(ARI),以及拉莫三嗪(200 mg/d)治疗相对于安慰剂治疗所致1例不良事件发生前需要治疗的患者数(NNH);显著性检验以95%可信区间(95%CI)表示.结果 (1)难治性精神分裂症4项、双相抑郁4项、难治性双相抑郁1项和重性抑郁症3项临床试验被分析;(2)在难治性精神分裂症、双相抑郁及难治性双相抑郁、重性抑郁症的急性治疗期,与安慰剂比较,拉莫三嗪(200 mg/d)相关不良事件引起治疗终止NNH(95%CI)依次为323(-23～20)、-47(-17～60)、-34(-10～22)和-32(-14～158)例,皮疹依次为133(-51～29)、-46(-18～83)、51(-16～10)和-31(-15～1208)例,头痛依次为-26(-11～61)、-168(-16～19)、-28(-6～9)和53(-24～13)例,差异无统计学意义(95%CI包括0).结论 拉莫三嗪单药或增效治疗精神分裂症、双相抑郁和重性抑郁症具有良好的耐受性与安全性.

Abstract：

Objective To compare the tolerability and sensitivity of lamotrigine in the treatment of schizophrenia, bipolar depression and major depressive disorder (MDD). Methods Data from randomized,double-blind, placebo-controlled trials of lamotrigine adjunctive or monotherapy in the acute treatment of treatment-resistant schizophrenia, bipolar depression, and MDD were used. The discontinuation due to adverse events (DAEs) was used as an index of tolerability. The reported headache and occurrence of rash were used as indexes of sensitivity. Absolute risk increase (ARI) and number needed to harm (NNH) of lamotrigine at dose of 200 mg/d relative to placebo for DAEs, headache, and rash were estimated with 95% confidence interval (CI) to reflect the magnitude of variance. Results Four trials in treatment-resistant schizophrenia, 4 in bipolar depression, 1 in treatment-resistant bipolar depression and 3 in major depressive disorder were analyzed. In the acute treatment of treatment-resistant schizophrenia, bipolar depression or treatment-resistant bipolar depression and major depressive disorder, lamotrigine 200 mg/d did not significantly increase the risk for DAEs [NNH 95% CI respectively as 323(-23 to 20) ,-47(-17 to 60), -34(-10 to 22) and-32(-14 to 158)], rash [NNH 95% CI respectively as 133 (-51 to 29),-46(-18 to 83), 51 (-16 to 10) and -31 (-15 to 1208)] and headache [NNH 95% CI respectively as -26(-11 to 61),-168 (-16 to 19),-28 (-6 to 9) and 53 (-24 to 13)] relative to placebo. Conclusion The available data indicate patients with schizophrenia, bipolar depression and major depressive disorder tolerate lamotrigine 200 mg/d as well as placebo and have a similar sensitivity to lamotrigine as to placebo.     

Fat cell-secreted adiponectin mediates physical exercise-induced hippocampal neurogenesis: an alternative anti-depressive treatment?

Psychological depression is drawing accumulating attention nowadays, due to the skyrocketing incidence worldwide and the enormous burdens it incurs. Physical exercise has been long recognized for its therapeutic effects on depressive disorders, although knowledge of the underlying mechanisms remains limited. Suppressed hippocampal neurogenesis in adult brains has been regarded, at least partly, contributive to depression, whereas physical exercise that restores neurogenesis accordingly exerts the anti-depressive action. Several recent publications have suggested the potential role of adiponectin, a protein hormone secreted by peripheral mature adipocytes, in mediating physical exercise-triggered enhancement of hippocampal neurogenesis and alleviation of depression. Here, we briefly review these novel findings and discuss the possibility of counteracting depression by modulating adiponectin signaling in the hippocampus with interventions including physical exercise and administration of pharmacological agents.     

Grey matter volume abnormalities in patients with bipolar I depressive disorder and unipolar depressive disorder:a voxelbased morphometry study

Bipolar disorder and unipolar depressive disorder(UD) may be different in brain structure. In the present study,we performed voxel-based morphometry(VBM) to quantify the grey matter volumes in 23 patients with bipolar I depressive disorder(BP1) and 23 patients with UD,and 23 age-,gender-,and educationmatched healthy controls(HCs) using magnetic resonance imaging. We found that compared with the HC and UD groups,the BP1 group showed reduced grey matter volumes in the right inferior frontal gyrus and middle cingulate gyrus,while the UD group showed reduced volume in the right inferior frontal gyrus compared to HCs. In addition,correlation analyses revealed that the grey matter volumes of these regions were negatively correlated with the Hamilton depression rating scores. Taken together,the results of our study suggest that decreased grey matter volume of the right inferior frontal gyrus is a common abnormality in BP1 and UD,and decreasedgrey matter volume in the right middle cingulate gyrus may be specifi c to BP1.     

扁平疣患者的抑郁情绪和细胞免疫功能的研究

Objective To evaluate the possible association between depression and cellular immunologic status in patients with verruca planea. Methods Depression was assessed with the Self-rating Depression Scale (SDS), and the inteleukin-2 (IL-2)produced by peripheral blood mononuclear cells (PBMC) and the activity of natural killer (NK) cells were measured in 68 patients with verruca planea. Results The SDS scores in patients with verruca planea(46. 08 ± 12.76) were significantly higher than those in the controls(41.88 ± 10. 57, t = 3.71, P ＜ 0. 01 ), and 38% of the patients were affected by depression. The mean scores of depression (48.89 ± 11. 52 ) and the rate ( 29% ) of depressive disorder among patients unmarried (single) were significantly higher than those married [(43. 16 ± 10. 17 ), 9%;t = 2. 28, x2 = 4. 86, P ＜ 0. 05] . The mean scores of depression among female patients (49. 01 ± 11.36 )were significantly higher than male patients [(41.96 ± 10.48 ) ,t =2. 21 ,P ＜0. 05] . In patients affected by depression, the level of the IL-2[(46. 64 ± 12. 28) × 103 U/L] produced by PBMC and the activity of NK cells[( 19. 23 ±5.60)%] were significantly decreased than those in undepressive group[(56. 15 ± 18. 32) ×103 U/L, (24.65 ± 6. 89)%; t = 3.18, 3. 32, P ＜ 0.01] . The differences above were all significant. Conclusions Patients with vermca planea are partly affected by depression and the cellular immunologic status may be abnormal among the patients with depression.     

The Immune System and the Role of Inflammation in Perinatal Depression

Major depression during pregnancy is a common psychiatric disorder that arises from a complex and multifactorial etiology. Psychosocial stress, sex, hormones, and genetic vulnerability increase the risk for triggering mood disorders. Microglia and toll-like receptor 4 play a crucial role in triggering wide and varied stress-induced responses mediated through activation of the inflammasome; this leads to the secretion of inflammatory cytokines, increased serotonin metabolism, and reduction of neurotransmitter availability along with hypothalamic–pituitary–adrenal axis hyperactivity. Dysregulation of this intricate neuroimmune communication network during pregnancy modifies the maternal milieu, enhancing the emergence of depressive symptoms and negative obstetric and neuropsychiatric outcomes. Although several studies have clearly demonstrated the role of the innate immune system in major depression, it is still unclear how the placenta, the brain, and the monoaminergic and neuroendocrine systems interact during perinatal depression. Thus, in the present review we describe the cellular and molecular interactions between these systems in major depression during pregnancy, proposing that the same stress-related mechanisms involved in the activation of the NLRP3 inflammasome in microglia and peripheral myeloid cells in depressed patients operate in a similar fashion in the neuroimmune placenta during perinatal depression. Thus, activation of Toll-like receptor 2 and 4 signaling and the NLRP3 inflammasome in placental immune cells may promote a shift of the Th1/Th2 bias towards a predominant Th1/Th17 inflammatory response, associated with increased secretion of pro-inflammatory cytokines, among other secreted autocrine and paracrine mediators, which play a crucial role in triggering and/or exacerbating depressive symptoms during pregnancy.     

Occurrence and influential factors of depression in patients with Alzheimer disease

BACKGROUND: The differential diagnosis between depressive pseudodementia and Alzheimer disease (AD) is a clinical problem, and it is more difficult to diagnose depression in AD. OBJECTIVE: To analyze the incidence and characters of depression in AD patients, and investigate the correlative factors. DESIGN: A randomized controlled study. SETTING: Beijing Geriatrics Hospital. PARTICIPANTS: From October 2005 to July 2006, 34 patients with probable AD were selected from the Department of Dementia, Beijing Geriatrics Hospital according to National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer Disease and Related Disorders Association (NINCDS-ADRDA) criteria for AD. There were 16 males and 18 females, aged 63-85 years. Meanwhile, 30 patients with other chronic neurological disorders (CND) were selected from our hospital as the CND control group, there were 16 males and 14 females, aged 55-85 years, including 18 cases of cerebrovascular sequela, 9 of Parkinson disease and 3 of migraineurs. Another 30 patients with chronic physical diseases (CPD) were enrolled as the CPD control group, there were 15 males and 15 females, aged 57-83 years, including 15 cases of chronic bronchitis, 8 of hypertension and 7 of diabetes mellitus. Besides, 30 physical examinees were enrolled as the healthy control group, including 15 males and 15 females, aged 55-80 years. All the subjects were informed and agreed with the detection. METHODS: ① All the subjects underwent the Hamilton rating scale for depression (HAMD) (24 items) assessment, and the total score < 8 points was regarded as no depression, 8-20 as mild depression, 20-35 as moderate depression, ≥ 35 as severe depression. ② All the AD patients were assessed with Cornell scale for depression in dementia (CSDD) (19 items), and the total score < 8 points was regarded as no depression, and ≥ 8 as depression. CSDD consisted of five subscales, including mood-related signs, behavioral disturbance, cyclic functions, ideational disturbance and physical signs, which were scored as 0-2 points respectively, and the abnormal rate of each factor was observed, the abnormal rate was the percentage of number of patients suffering from the symptoms in the subscales to the total number of patients. ③ The cognitive function of the AD patients was assessed with Mini-mental status examination (MMSE) (the total score ranged 0-30 points; ≤17 in illiterate, ≤ 20 in primary school and ≤ 24 in middle school and higher was regarded as cognitive deficit) and the daily living ability of the AD patients was assessed with ADL. MAIN OUTCOME MEASURES: ① HAMD scores in all the groups; ② CDSS scores and abnormal rate of factors in AD patients; ③ MMSE score and activity of daily life (ADL) score in AD patients; ④ Correlation between depression and correlative factors in AD patients. RESULTS: All the 124 subjects were involved in the analysis of results. ① The HAMD average score of the AD group was significantly higher than those of the CND, CPD and healthy control groups [(12.7±3.2), (5.5±2.5), (3.4±1.3), (2.6±1.7) points, P < 0.01]. ② In the AD group, the CDSS average score was (5.8±4.3) points, 41.2% (14/34) met the criteria for depression. The abnormal rates in order were 44% (15/34) for mood-related signs, 32% (11/34) for behavioral disturbance, 24% (8/34) for cyclic function, 12% (4/34) for ideational disturbance and 12% (4/34) for physical signs. ③ The factors of age, course, MMSE score and ADL score were finally excluded after a multiple regression (P > 0.05). There was a negative correlation between CSDD score and onset age (P < 0.05), sex was also obviously correlated with CSDD score (P < 0.05). CONCLUSION: The incidence of depression in AD is much higher with various manifestations. Female patients are the susc and earlier onset age is the risk factor for the presence of depression in AD.     

抑郁症患者治疗前后血浆孤啡肽的研究

Objective To explore the changes of plasma orphanin FQ (OFQ) level in depressive patients before and after treatment. Methods The plasma OFQ levels of 38 depressive patients were determined with radioimmunoassay at baseline and after 8 week antidepressant treatment, and 32 healthy persons were examined once as controls. Results The concentrations of OFQ in patients were significantly higher at baseline than after treatent and in controls [(21.9 ± 2. 3 ) ng/L vs. ( 10. 9 ± 2. 1 ) ng/L; (21.9±2. 3) ng/L vs. (10. 2 ± 1.8 )ng/L; all P < 0. 01]. There were no significant differences in OFQ between patients after treatment and in controls. The OFQ concentration in patients at baseline was positively correlated to the scores of 24-items Hamilton Depression Scale (HAMD) (r =0. 857,P <0. 01 ), the change of OFQ concentration between baseline and after treatment was also positively correlated to the alteration of HAMD scores (r = 0. 342, P < 0. 05 ). Conclusions The results suggest that the alteration of OFQ may be involved in depression.     

Exploration of the mechanism by which icariin modulates hippocampal neurogenesis in a rat model of depression

Icariin(ICA) has a significant capacity to protect against depression and hippocampal injury,but it cannot effectively cross the bloodbrain barrier and accumulate in the brain.Therefore,the mechanism by which ICA protects against hippocampal injury in depression remains unclear.In this study,we performed proteomics analysis of cerebrospinal fluid to investigate the mechanism by which ICA prevents dysfunctional hippocampal neurogenesis in depression.A rat model of depression was established through exposure to chronic unpredictable mild stress for 6 weeks,after which 120 mg/kg ICA was administered subcutaneously every day.The results showed that ICA alleviated depressive symptoms,learning and memory dysfunction,dysfunctional neurogenesis,and neuronal loss in the dentate gyrus of rats with depression.Neural stem cells from rat embryonic hippocampi were cultured in media containing 20% cerebrospinal fluid from each group of rats and then treated with 100 μM corticosterone.The addition of cerebrospinal fluid from rats treated with ICA largely prevented the corticosterone-mediated inhibition of neuronal proliferation and differentiation.Fifty-two differentially expressed proteins regulated by chronic unpredictable mild stress and ICA were identified through proteomics analysis of cerebrospinal fluid.These proteins were mainly involved in the ribosome,PI3 K-Akt signaling,and interleukin-17 signaling pathways.Parallel reaction monitoring mass spectrometry showed that Rps4 x,Rps12,Rps14,Rps19,Hsp90 b1,and Hsp90 aa1 were up-regulated by chronic unpredictable mild stress and down-regulated by ICA.In contrast,Htr A1 was down-regulated by chronic unpredictable mild stress and up-regulated by ICA.These findings suggest that ICA can prevent depression and dysfunctional hippocampal neurogenesis through regulating the expression of certain proteins found in the cerebrospinal fluid.The study was approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2017.