Decreased Total Antioxidant Activity in Major Depressive Disorder Patients Non-Responsive to Antidepressant Treatment

Objective

This study aimed to evaluate the total antioxidant activity (TAA) in patients with major depressive disorder (MDD) and the effect of antidepressants on TAA using a novel potentiometric method.

Methods

Twenty-eight patients with MDD and thirty-one healthy controls were enrolled in this study. The control group comprised 31 healthy individuals matched for gender, drinking and smoking status. We assessed symptoms of depression using the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI). We measured TAA using potentiometry. All measurements were made at baseline and four and eight weeks later.

Results

There was a significant negative correlation between BDI scores and TAA. TAA was significantly lower in the MDD group than in controls. When the MDD group was subdivided into those who showed clinical response to antidepressant therapy (response group) and those who did not (non-response group), only the non-response group showed lower TAA, while the response group showed no significant difference to controls at baseline. After eight weeks of antidepressant treatment, TAA in both the response and non-response groups was similar, and there was no significant difference among the three groups.

Conclusion

These results suggest that the response to antidepressant treatment in MDD patients might be predicted by measuring TAA.     

Predisposition to treatment response in major depressive episode: A peripheral blood gene coexpression network analysis

Antidepressant efficacy is insufficient, unpredictable and poorly understood in major depressive episode (MDE). Gene expression studies allow for the identification of significantly dysregulated genes but can limit the exploration of biological pathways. In the present study, we proposed a gene coexpression analysis to investigate biological pathways associated with treatment response predisposition and their regulation by microRNAs (miRNAs) in peripheral blood samples of MDE and healthy control subjects. We used a discovery cohort that included 34 MDE patients that were given 12-week treatment with citalopram and 33 healthy controls. Two replication cohorts with similar design were also analyzed. Expression-based gene network was built to define clusters of highly correlated sets of genes, called modules. Association between each module’s first principal component of the expression data and clinical improvement was tested in the three cohorts. We conducted gene ontology analysis and miRNA prediction based on the module gene list. Nine of the 59 modules from the gene coexpression network were associated with clinical improvement. The association was partially replicated in other cohorts. Gene ontology analysis demonstrated that 4 modules were associated with cytokine production, acute inflammatory response or IL-8 functions. Finally, we found 414 miRNAs that may regulate one or several modules associated with clinical improvement. By contrast, only 12 miRNAs were predicted to specifically regulate modules unrelated to clinical improvement. Our gene coexpression analysis underlines the importance of inflammation-related pathways and the involvement of a large miRNA program as biological processes predisposing associated with antidepressant response.     

临床痊愈在抑郁症治疗中的意义及用药选择

抑郁症是一种常见、慢性且容易复发的精神疾病,发病率较高,在全世界范围内8％～12％在一生中会患有抑郁症。抑郁症会给患者带来极大的健康负担和经济负担,同时也会严重影响患者的社会功能和生活质量。世界卫生组织预计,至2020年抑郁症会成仅次于缺血性心脏病的全球第二大影响伤残调整生命年（disability—adjusted lif eyear,DALY）的疾病。     

抗抑郁治疗对腹泻型肠易激综合征患者肠道敏感性的影响

目的 观察腹泻型肠易激综合征(IBS-D)伴抑郁状态患者抗抑郁治疗前后症状积分、汉密尔顿抑郁量表(HAMD)积分及直肠敏感性的变化,评价抗抑郁药物在IBS-D治疗中的作用.方法 依据RomeⅢ标准和CCMD3标准将符合IBS-D伴抑郁状态的患者随机分为研究组和对照组,前者给予常规治疗加抗抑郁药物及心理疏导,后者给予常规药及对症治疗.治疗前后分别进行症状积分、HAMD积分及直肠敏感性测定,并进行统计学分析.结果 研究组与对照组治疗后及研究组治疗前后症状积分、HAMD积分、直肠敏感性比较差异均有统计学意义(P<均0.01).结论 伴抑郁状态的IBS-D患者加用抗抑郁药物能减轻临床症状,降低肠道敏感性,从而改善与之相关的疼痛,其疗效优于对照组. Abstract： Objective To evaluate the effect of antidepressant treatment for the diarrhea-predominant irritable bowel syndrome(IBS-D),by observing the changes of clinical symptom score,HAMD scale score and the regulation of intestinal sensations in IBS-D with depress patients before and after treatment. Methods Accord to ROMEⅢ standard and CCMD3 standard,all IBS-D with depress patients were randomly divided into two groups. The study group was given antidepressant treatment plus conventional treatment and mental adjustment treatment, and the control group was given conventional treatment.All the cases received symptom score,HAMD scale score evaluating and evaluating the regulation of intestinal sensations before and after antidepressant treatment. Results The study group comparing with the control group after treatment and the study group itself before treatment comparing with after treatment, was significantly different in symptoms score, HAMD score, and the regulation of visceral sensations (all P<0.01). Conclusions For the patients of IBS with depress using antidepressant drug can significantly alleviate the physical symptoms, and antidepressant treatment can improvethe threshold of visceral sensation and alleviate the physical symptom such as pain.     

抗抑郁药阿戈美拉汀合成综述

抑郁症的发病率逐年增高,抗抑郁药物的开发和利用也越来越受到国外跨国企业的关注。阿戈美拉汀是2009年刚在欧盟上市的第一个褪黑激素类抗抑郁药,能有效治疗抑郁症,改善睡眠参数和保持性功能。本文介绍了抗抑郁药的种类,总结了阿戈美拉汀合成路线并简要介绍了其应用前景。     

The Wnt Pathway in Mood Disorders

Objectives:

To review the evidence of the involvement of the Wnt signalling pathway in mood disorders and in the action of drugs used to treat these disorders.

Methods:

We performed a careful PubMed search using as keywords all possible terms relevant to the Wnt pathway and crossing them with each of four areas, i.e., developmental effects, behavioural effects, mood disorders, and drugs used in their treatment. Papers were selected on the basis of their content and their data used for discussion.

Results:

Neurodevelopmental and behavioural data point to the possibility of involvement of the Wnt pathway in the pathophysiology of mood disorders. Clinical and post-mortem data are not sufficient to corroborate a definite role for Wnt alterations in any mood disorder. Combining genetic and pharmacological data, we may state that glycogen synthase kinase is the key molecule in bipolar disorder, as it is connected with many other signalling pathways that were shown to be involved in mood disorders, while Wnt molecules in the hippocampus appear to be mainly involved in depressive disorders.

Conclusions:

Altered Wnt signalling may play a role in the pathophysiology of mood disorders, although not a central one. It is premature to draw conclusions regarding the possible usefulness of Wnt manipulations in the treatment of mood disorders.     

Tryptophan hydroxylase 2 gene is associated with major depressive disorder in a female Chinese population

Background

Previous candidate gene studies of major depressive disorder (MDD) have provided inconclusive evidence of association for genes with strong biological rationale for MDD. In this study, we aimed to investigate the association of tryptophan hydroxylase 2 gene with MDD and its treatment response in the Chinese Han population.

Methods

Three hundred and sixty eight depressed patients who met DSM-IV criteria for major depressive disorder were recruited for the study. 371 normal controls were recruited from local community. Patients and normal controls were genotyped for TPH2 (rs4290270 and rs7305115) variants by polymerase chain reaction. Male and female subjects were analyzed separately.

Results

No differences were found in the frequencies of the single alleles and genotypes of the tested polymorphisms between MDD patients and normal group. The frequency of the A-A haplotype was significantly higher in female MDD compared to healthy female controls (P < 0.05). No significant association with treatment response was discovered in haplotype and single-marker analysis.

Limitations

This study lacks a placebo control and we cannot definitively exclude the possibility that some patients in the responder group responded to the placebo effect alone.

Conclusion

The result suggests that TPH2 gene may have a gender dependent effect on susceptibility to MDD but not with its treatment response in Chinese Han population. Further studies are needed to replicate the association that we observed.     

Serotonin-1A receptors in the dorsal periaqueductal gray matter mediate the panicolytic-like effect of pindolol and paroxetine combination in the elevated T-maze

The β-adrenergic blocker and 5-HT_1A receptor antagonist pindolol has been combined with selective serotonin reuptake inhibitors (SSRIs) in patients with depressive and anxiety disorders to shorten the onset of the clinical action and/or increase the proportion of responders. The results of a previous study have shown that pindolol potentiates the panicolytic effect of paroxetine in rats submitted to the elevated T-maze (ETM). Since reported evidence has implicated the 5-HT_1A receptors of the dorsal periaqueductal gray matter (DPAG) in the panicolytic effect of antidepressants, rats treated with pindolol (5.0 mg/kg, i.p.) and paroxetine (1.5 mg/kg, i.p.) received a previous intra-DPAG injection of the selective 5-HT_1A antagonist, WAY-100635 (0.4 μg) and were submitted to the ETM. Pretreatment with WAY-100635 reversed the increase in escape latency, a panicolytic effect, determined by the pindolol-paroxetine combination. These results implicate the 5-HT_1A receptors of the DPAG in the panicolytic effect of the pindolol-paroxetine combination administered systemically. They also give further preclinical support for the use of this drug combination in the treatment of panic disorder.     

Role of different types of potassium channels and peroxisome proliferator-activated receptors γ in the antidepressant-like activity of bis selenide in the mouse tail suspension test

In the present study we investigated the role of potassium (K(+)) channels and peroxisome proliferator-activated receptor gamma (PPARγ) in the antidepressant-like effect of bis selenide in the mouse tail suspension test (TST). Intracerebroventricular (i.c.v.) pretreatment with tetraethyl ammonium (TEA, a non-specific inhibitor of K(+) channels, 25 pg/site), glibenclamide (an ATP-sensitive K(+) channel inhibitor, 0.5 pg/site), charybdotoxin (a large and intermediate conductance calcium-activated K(+) channel inhibitor, 25 pg/site) or apamin (a small-conductance calcium-activated K(+) channel inhibitor, 10 pg/site) produced a synergistic action with a sub effective dose of bis selenide (0.1 mg/kg, per oral--p.o.). Picrotoxin (1 mg/kg, intraperitoneally--i.p.) pretreatment did not prevent the reduction in immobility time elicited by bis selenide (1 mg/kg, p.o.) in the TST. The reduction in the immobility time elicited by an effective dose of bis selenide (1 mg/kg, p.o.) was prevented by the pretreatment of mice with cromakalim, minoxidil (K(+) channel openers, 10 μg/site, i.c.v.) and GW 9662 (a PPARγ antagonist, 10 μg/site, i.c.v.). The findings clearly suggest that an acute oral dose of bis selenide produced an antidepressant-like effect in the mouse TST by a mechanism that involves the K(+) channels and PPARγ receptors.