Moderate exercise improves depression parameters in treatment-resistant patients with major depressive disorder

Background

Treatment-resistant major depressive disorder (MDD) is a complex condition, with very low remission rates. Physical exercise has been used, with some encouraging results, as an alternative therapy in other depressive disorders. This study assessed the impact on depression and functioning parameters of a moderate intensity exercise program, as an adjuvant to pharmacotherapy, in treatment-resistant MDD patients.

Methods

150 individuals with treatment-resistant MDD, defined as taking combined therapy in doses considered adequate for 9-15 months, without showing clinical remission, were initially screened. 33 were randomized to one of two groups: usual pharmacotherapy (N = 11) and usual pharmacotherapy plus aerobic exercise (N = 22). The exercise program consisted of home-based 30-45 min/day walks, 5 days/week, for 12 weeks, being 1 walk per week supervised.

Results

The exercise group showed improvement of all depression and functioning parameters, as indicated by lower HAMD17, BDI and CGI-S and higher GAF (p < 0.05) at last observation compared both to baseline values and to control group. At the end of the study none of the participants in the control group showed response or remission, whilst in the exercise group 21% of participants showed response and 26% remission, although these differences were not statistically significant.

Conclusion

A 12 week, home-based exercise program of 30-45 min/day walks, 5 days/week, improved depression and functioning parameters in treatment-resistant MDD patients, and contributed to remission of 26% of these patients. Moderate intensity exercise may be a helpful and effective adjuvant therapy for treatment-resistant MDD.     

The role of nesfatin-1 in impaired appetite in patients with major depressive disorder

AimThe aim of the present study was to explore whether plasma nesfatin-1 levels are associated with impaired appetite in major depressive disorder (MDD).MethodsPatients were recruited from outpatients who consecutively sought treatment in the psychiatric outpatient clinic of the University Hospital since March 2012. All patients were diagnosed with major depressive disorder according to DSM-IV. The appetite of patients was assessed by specific questionnaire. We categorized patients into two groups according to their appetite. Study group consisted of 30 patients with increased appetite (MDD-IA), 28 patients with decreased appetite (MDD-DA) and 28 healthy controls. Plasma nesfatin-1 levels and body mass index (BMI) were measured.ResultsThere was no statistically significant difference in nesfatin-1 between groups. The mean serum nesfatin-1 level did not show any correlation with age, BMI, HAM-D scores and fasting blood glucose in patients groups.ConclusionOur findings suggest that fasting plasma nesfatin-1 levels are unchanged in untreated MDD patients and there is no evidence for nesfatin-1 playing a role in impaired appetite in patients with MDD.     

阿戈美拉汀治疗重度抑郁症的临床疗效

目的 探讨新型抗抑郁药物阿戈美拉汀在治疗重度抑郁患者方面的临床疗效和安全性.方法 选取我院2013年2月～2014年2月收住院的重度抑郁症患者58例随机分为两组,研究组应用阿戈美拉汀25～50mg/d,平均剂量（46.36±4.48）mg/d,对照组选用艾司西酞普兰10～20mg/d,平均剂量（16.83±2.94）mg/d,均治疗8周.治疗前及治疗后第2,4,8周分别采用汉密尔顿抑郁量表（HAMD-17）对两组进行评估,在治疗过程中应用治疗不良反应量表（TESS）进行测量.结果 治疗2周后研究组HAMD减分为（8.36±4.07）分,对照组为（6.19±3.68）分,两组减分情况比较差异有统计学意义（q=3.38,P＜0.05）.治疗8周后阿戈美拉汀组HAMD减分为（18.15±4.29）分,艾司西酞普兰组HAMD减分为（16.26±3.83）分,两组减分情况比较差异有统计学意义（q=4.12,P＜ 0.05）.药物安全性方面,研究组主要不良反应依次是头痛（5例）、便秘（4例）和肝功能异常（3例）;对照组主要不良反应依次是头痛（9例）、恶心呕吐（6例）和血压升高（5例）.TESS总分比较,研究组（3.42±1.24）分低于对照组（4.08±1.69）分,差异有统计学意义（t=7.45,P＜0.01）.结论 阿戈美拉汀在治疗重度抑郁症方面,较艾司西酞普兰起效快,疗效明显,不良反应少.     

Predictors of depressive symptoms at hospital discharge in patients with major depressive disorder

Abstract

Objective. Often patients with major depressive disorder (MDD) leave the hospital with continued significant symptomatology. This study sought to evaluate demographic, clinical, and psychosocial predictors of the presence of clinically significant depressive symptoms, defined as a Modified Hamilton Rating Scale for Depression score of ≥ 14, immediately following hospitalization for MDD. Methods. The study enrolled 135 patients with MDD as part of a larger clinical trial investigating the efficacy of post-hospitalization pharmacologic and psychosocial treatments for depressed inpatients. Structured clinical interview and self-report data were available from 126 patients at hospital admission and discharge. Results. Despite the significant decreases in depressive symptoms over the course of hospitalization, 91 (72%) displayed clinically significant depressive symptoms at discharge. Multivariate logistic regression analysis revealed that female sex, earlier age of onset, and poorer social adjustment were unique predictors of symptom outcome. Conclusions. Results suggest that a large proportion of patients leave the hospital with continued significant symptomatology, and the presence of such symptoms following hospitalization for MDD is likely to be explained by a combination of factors.     

Duloxetine-induced liver injury in patients with major depressive disorder

Duloxetine is a balanced serotonin-norepinephrine reuptake inhibitor. Duloxetine-induced liver injury in patients with preexisting liver disease or chronic alcohol use is known. However, we have found that duloxetine can also induce liver injury in cases without those risk factors. We recommend that clinicians should monitor liver function carefully following duloxetine treatment.     

Ego-rotation and object-rotation in major depressive disorder

Mental rotation (MR) performance provides a direct insight into a prototypical higher-level visuo-spatial cognitive operation. Previous studies suggest that progressive slowing with an increasing angle of orientation indicates a specific wing of object-based mental transformations in the psychomotor retardation that occurs in major depressive disorder (MDD). It is still not known, however, whether the ability of object-rotation is associated with the ability of ego-rotation in MDD. The present study was designed to investigate the level of impairment of mental transformation abilities in MDD. For this purpose we tested 33 MDD (aged 18–52 years, 16 women) and 30 healthy control subjects (15 women, age and education matched) by evaluating the performance of MDD subjects with regard to ego-rotation and object-rotation tasks. First, MDD subjects were significantly slower and made more errors than controls in mentally rotating hands and letters. Second, MDD and control subjects displayed the same pattern of response times to stimuli at various orientations in the letter task but not the hand task. Third, in particular, MDD subjects were significantly slower and made more errors during the mental transformation of hands than letters relative to control subjects and were significantly slower and made more errors in physiologically impossible angles than physiologically possible angles in the mental rotation hand task. In conclusion, MDD subjects present with more serious mental rotation deficits specific to the hand than the letter task. Importantly, deficits were more present during the mental transformation in outward rotation angles, thus suggesting that the mental imagery for hands and letters relies on different processing mechanisms which suggest a module that is more complex for the processing of human hands than for letters during mental rotation tasks. Our study emphasises the necessity of distinguishing different levels of impairment of action in MDD subjects.     

Plasminogen activator inhibitor-1 4G/5G polymorphism in breast cancer patients and its association with tissue PAI-1 levels and tumor severity

BACKGROUND: The plasminogen activator inhibitor type 1 (PAI-1) 4G/5G polymorphism may have significance for PAI-1 expression. High levels of PAI-1 in breast cancer patients are associated with a poor prognosis. In this study, we analyzed the influence of the PAI-1 4G/5G polymorphism on tissue PAI-1 levels and its association with tumor severity in women with breast cancer. MATERIAL AND METHODS: We studied 104 women with breast carcinoma (patient group) and 104 healthy age-matched women (control group). In patients and controls, the PAI-1 4G/5G polymorphism was determined by PCR amplification using allele-specific primers. In patients, PAI-1 levels were quantified in breast cancer tissue by using an ELISA. RESULTS: The frequency of the PAI-1 4G allele tended to be higher in patients than in controls (p=0.062). The presence of the 4G allele (4G/5G plus 4G/4G genotypes) was significantly higher among patients with histological grade 3 tumors than among those with grade 1 tumors (p=0.026). Furthermore, patients with the 4G/4G genotype had significantly higher tissue PAI-1 levels than those with the 5G/5G genotype. Moreover, tissue PAI-1 antigen levels were significantly and positively correlated with tumor severity (p=0.003) and tumor size (p=0.009). However, no significant differences in PAI-1 level were observed in relation to menopause, hormone receptor or nodal status. CONCLUSION: Tissue PAI-1 antigen levels and tumor severity seem to be associated with the PAI-1 4G/5G polymorphism. Further studies with a larger number of patients are needed to clarify the influence of this polymorphism in breast cancer.     

Ambient temperature affects thrombotic potential at rest and following exercise

Introduction

During exercise, ischemic risk increases, possibly due to changes in coagulation and fibrinolytic activity. Previous research suggests ambient temperature affects resting thrombotic potential, but the effect of heat and cold on hemostasis during exercise is unknown. The purpose of this study was to assess changes in coagulation and fibrinolysis during maximal exercise in hot and cold temperatures, and to compare those responses to exercise under temperate conditions.

Materials & Methods

Fifteen healthy men completed maximal exercise tests in hot (30 °C), temperate (20 °C) and cold (5° - 8 °C) temperatures. Blood samples were obtained before and immediately after exercise and analyzed for concentrations of thrombin-antithrombin III (TAT), active tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1). Results were analyzed by ANOVA.

Results

A main effect of time was observed for TAT (temperate = 1.71 ± 0.82 - 2.61 ± 0.43 ng/ml, hot = 1.81 ± 0.73 - 2.62 ± 0.67 ng/ml, cold = 2.33 ± 0.65 - 2.89 ± 0.81 ng/ml, PRE to POST, respectively) and tPA activity (temperate = 0.72 ± 0.44 - 2.71 ± 0.55 IU/ml, hot = 0.72 ± 0.38 - 2.64 ± 0.61 IU/ml, cold = 0.86 ± 0.45 - 2.65 ± 0.77 IU/ml, PRE to POST, respectively). A trend was observed for the PAI-1 response to exercise (temperate = 14.5 ± 23.7 - 12.3 ± 20.2 IU/ml, hot = 15.1 ± 26.5 - 10.0 ± 15.1 IU/ml, cold = 10.5 ± 10.4 - 7.9 ± 9.7 IU/ml, PRE to POST, respectively, p = 0.08). TAT concentrations were significantly higher in cold compared to temperate and hot conditions.

Conclusion

Coagulation potential is elevated during exposure to cold temperatures. These data suggest that risk of an ischemic event may be elevated in the cold.     

Effects of venlafaxine and fluoxetine on lymphocyte subsets in patients with major depressive disorder: A flow cytometric analysis

Background

Studies have yielded conflicting results concerning flow cytometric lymphocyte analyses in patients with depression. Data about the effect of antidepressants on lymphocyte subsets are also contradictory. The aim of this study was to determine effects of venlafaxine versus fluoxetine on lymphocyte subsets in depressive patients.

Methods

Sixty-nine patients diagnosed with major depressive disorder (MDD) according to DSM-IV and 36 healthy controls are included in the study. Sixty-nine patients were randomized to take fluoxetine (FLX) (n = 33) or venlafaxine (VEN) (n = 36). Serum lymphocyte subsets included CD3, CD4, CD8, CD16/56, CD19, CD45, Anti-HLA-DR which were measured by flow cytometric analyses at baseline and 6 weeks after the start of treatment. The severity of depression was evaluated with Hamilton rating scale for depression.

Results

At baseline, patients with MDD had significantly lower CD16/56 ratio and higher CD45 ratio compared to the controls. Although numerically higher in the VEN treated patients, treatment response rates between the FLX (53%) and the VEN (75%) groups were not different statistically. CD45 values decreased significantly in the VEN group at the end of the 6 week treatment period whereas no difference was observed in the FLX group. By the 6th week, treatment responders showed a significantly higher CD16/56 ratio than non-responders. Baseline severity of depression and anxiety was positively correlated with baseline CD45 ratio and negatively correlated with baseline CD16/56 ratio. We did not observe consistent changes in the absolute number of circulating B or T cells, nor in the helper/inducer (CD4) or suppressor/cytotoxic (CD8) subsets.

Conclusions

CD16/56 was lower in patients with MDD and increased in treatment responders at 6th week. CD45 ratio was higher in patients with MDD than healthy subjects; it decreased with antidepressant treatment and was positively correlated with the severity of depression. Antidepressant treatment contributes to immune regulation in patients with major depressive disorder.     

社会支持对重性抑郁障碍患者自杀意念的影响

目的探讨社会支持对重性抑郁障碍(MDD)患者自杀意念的影响,为临床降低其自杀意念、减少自杀行为的发生提供参考。方法采用二阶段调查法,以在武汉市精神卫生中心门诊就诊的、符合《精神障碍诊断与统计手册(第4版)》(DSM-IV)诊断标准的1135例MDD患者为研究对象。采用患者健康问卷抑郁量表(PHQ-9)、社会支持评定量表(SSRS)进行调查,采用二元Logistic回归分析探讨MDD患者自杀意念的影响因素。结果1135例MDD患者中,有688例(60.62%)存在自杀意念,有自杀意念者PHQ-9评分高于无自杀意念者,差异有统计学意义[(14.18±5.02)分vs.(11.07±4.61)分,t=10.497,P<0.01]。有自杀意念者的主观支持、对支持的利用度及SSRS总评分均低于无自杀意念者,差异均有统计学意义(P均<0.01)。以自杀意念为因变量,以客观支持、主观支持、对支持利用度及PHQ-9评分为自变量的二元Logistic回归模型为logit(P)=-0.286+0.026X1-0.035X2-0.063X3+0.128X4,其中主观支持和抑郁均对自杀意念有预测作用(B=-0.035、0.128,P<0.05或0.01)。结论存在抑郁症状及缺乏社会支持(尤其是主观支持)可能是MDD患者出现自杀意念的危险因素。     

Episodic simulation of future events is impaired in patients with major depressive disorder

We examined future episodic simulation in patients with major depressive disorder (MDD) using a method that distinguishes between episodic and non-episodic details of events. Patients were impaired at generating specific episodic details concerning future events; non-episodic details were not affected. In addition, all participants generated more episodic details for positive than for negative stimulus words. These results suggest a deficit in autonoetic awareness among patients with MDD. Difficulties imagining future events may impact upon the success of therapeutic interventions aimed at altering biases in the prediction of positive and negative future happenings.     

Mismatch negativity in patients with major depressive disorder: A meta-analysis

ObjectiveDeficits of mismatch negativity (MMN), a general index of echoic memory function, have been documented in patients with schizophrenia. However, it remains controversial whether patients with major depressive disorder (MDD) demonstrate MMN defects compared with healthy controls (HC).MethodsAfter screening 41 potential studies identified in PubMed and Medline, 13 studies consisting of 343 HC and 339 patients with MDD were included in the present meta-analysis. The effect sizes (Hedges’s g) with a random-effect and inverse-variance weighted model were estimated for the MMN amplitudes and latencies. The effects of different deviant types (i.e., frequency and duration) and of different illness stages (i.e., acute and chronic) on MMN were also examined.ResultsWe found that 1) MMN amplitudes (g = 1.273, p < 0.001) and latencies (g = 0.303, p = 0.027) to duration, but not frequency deviants, were significantly impaired in patients with MDD compared to HC; 2), acute patients exhibited lower MMN amplitudes (g = 1.735, p < 0.001) and prolonged MMN latencies (g = 0.461, p = 0.007) for the duration deviants compared to HC. Only the attenuated duration MMN amplitudes were detected in patients with chronic MDD (g = 0.822, p = 0.027); and 3) depressive symptoms did not significantly correlate with MMN responses.ConclusionsPatients with MDD demonstrated abnormal MMN responses to duration deviants compared to HC.SignificanceDuration MMN may constitute an electrophysiological indicator to differentiate HC from patients with MDD, particularly those in the acute stage.     

Differences in depressive thoughts between major depressive disorder, IFN-alpha-induced depression, and depressive disorders among cancer patients

OBJECTIVE: The objective of this study is to test the hypothesis that there are differences in the distribution of negative thoughts among major depressive disorders (MDD), depressive disorders among cancer patients, and IFN-alpha-induced depression. METHODS: Twenty-three patients affected by MDD, 25 cancer patients affected by depressive disorders (20 MDD), and 19 patients affected by IFN-alpha-induced depression satisfying MDD criteria were evaluated using the 17-item Hamilton Depression Rating Scale and the 13-item Beck Depression Inventory. RESULTS: Sense of guilt was higher among MDD patients (56.5%) and was lower among cancer patients (4%) (P<.0001). Sense of failure, dissatisfaction, and self-dislike were higher among MDD patients than among IFN-alpha patients (P<.0001). CONCLUSIONS: In our study, patients affected by MDD present a different pattern of symptoms in comparison with patients affected by IFN-alpha-induced depression and depressive disorders. In particular, core depressive thoughts were less frequent in the last two conditions.     

伴非典型特征的抑郁症患者自杀未遂的危险因素分析

目的探讨伴非典型特征抑郁症患者自杀未遂的社会人口学及临床特征方面危险因素。方法来自全国13个中心的1172例抑郁症患者,纳入其中179例伴非典型特征患者,依据简明国际神经精神访谈(the Mini International Neuropsychiatric Interview,MINI)5.0中文版自杀模块的访谈结果,分为自杀未遂组和无自杀未遂组,通过多因素logistic回归分析伴非典型特征的抑郁症患者在性别、年龄等社会人口学资料及伴焦虑症状、伴精神病性症状等临床特征方面可能与自杀未遂相关的危险因素。结果伴非典型特征抑郁症患者自杀未遂的发生率为23.5%(42/179)。与无自杀未遂组患者相比,自杀未遂组患者更多伴有自杀观念、产后起病,更常使用抗抑郁剂以外的其他药物治疗(如抗精神病药、情感稳定剂及苯二氮类药)(均P0.05)。多因素logistic回归分析显示,既往住院次数(OR=1.730,95%CI:1.093~2.740)和自杀观念(OR=3.899,95%CI:1.506~10.092)与伴非典型特征的抑郁症患者发生自杀未遂相关(均P0.05)。结论既往住院次数多及伴有自杀观念是伴非典型特征抑郁症患者自杀未遂的主要危险因素。     

Serum brain-derived neurotrophic factor level in dysthymia: a comparative study with major depressive disorder

In this present work, it is aimed to demonstrate BDNF serum concentrations in patients with dysthymia and to compare them with BDNF serum concentrations in patients with major depressive disorder and healthy subjects. The study was carried out in Celal Bayar University Hospital, Manisa, Turkey. Seventeen patients with dysthymia, 24 patients with major depressive disorder and 26 subjects without any psychiatric diagnosis and any psychiatric treatment were included in the study. The severity of depression was assessed with 17-item HAM-D. All subjects were asked to give their written consent. Blood samples were collected at baseline. Serum BDNF was kept at -70 degrees C before testing, and assayed with an ELISA Kit (Promega; Madison, WI, USA), after dilution with the Block and Sample solution provided with the kit. The data were subjected to the analysis of variance. The BDNF serum concentrations of the dysthymia group (mean=28.9+/-9.2 ng/ml) were significantly higher than that of the major depressive disorder group (21.2+/-11.3 ng/ml) (p=0.002), and it was not different from the level of the control group (31.4+/-8.8 ng/ml). BDNF serum concentrations and HAM-D score did not have any significant correlation in the dysthymia and major depression groups (r=-0.276, p=0.086). The low level of BDNF in patients with dysthymic disorder seems to point out that BDNF changes in mood disorders are state-dependent and vary according to the severity of depressive episodes.     

Electroconvulsive therapy modulates critical brain dynamics in major depressive disorder patients

BackgroundElectroconvulsive therapy (ECT) is widely considered as an effective and fast-acting option for treating patients with major depressive disorder (MDD). However, the neural basis underlying this powerful therapy remains uncertain. Recent studies have suggested that the healthy brain may operate near a critical state, which may reflect a balance between neuronal excitation and inhibition.ObjectiveIn the present study, we investigated whether there are any changes regarding criticality in MDD and, if so, whether ECT can reverse them. Critical dynamics analyses were performed on resting-state functional magnetic resonance imaging (rs-fMRI) data collected from 39 MDD patients and 38 healthy controls (HCs).ResultsWe found that compared with HCs, MDD patients, especially those who responded positively to ECT, tended to have smaller average avalanch sizes and lower branching ratios, suggesting a sub-critical state, at both the whole-brain and functional network levels. Importantly, ECT effectively corrected such anomalies, accompanied by enhanced degree centrality and functional connectivity of high-degree nodes located in the networks including the default-mode and the frontoparietal networks.ConclusionThese results indicate that ECT can modulate large-scale brain dynamics of MDD patients to be closer to criticality. Our study sheds new light on the pathology of MDD and the network mechanism by which ECT influences treatment.