Electroconvulsive therapy (ECT) and aerobic exercise training (AET) increased plasma BDNF and ameliorated depressive symptoms in patients suffering from major depressive disorder

BackgroundTo treat patients suffering from major depressive disorder (MDD), research has focused on electroconvulsive therapy (ECT) and aerobic exercise training (AET). Brain derived neurotrophic factor (BDNF) seems to be key in MDD. The aims of the present study were therefore two-fold, to investigate in a three-arm interventional study the differential effects of ECT, ECT plus AET, and AET alone in patients suffering from TR-MDD on 1. depressive symptoms and 2. plasma BDNF (pBDNF).Methods60 patients with MDD (mean age: 31 years; 31.6% female patients) were randomly assigned either to the ECT, ECT + AET, or AET condition. The AET condition consisted of treadmill exercise for 45 min, three times a week. Both depression severity and pBDNF levels were assessed at baseline and 4 weeks later. All patients were further treated with an SSRI standard medication.ResultspBDNF levels increased over time in all three study conditions, though, highest increase was observed in the ECT + EAT condition, and lowest increase was observed in the AET condition. Depressive symptoms decreased in all three conditions over time, though, strongest decrease was observed in the ECT + AET condition. The combination of ECT + AET led to significantly greater remission rates than in either the ECT or AET alone conditions. BDNF levels were not associated with symptoms of depression.ConclusionsThe pattern of results suggests that ECT, AET and particularly their combination are promising directions for the treatment of patients suffering from MDD, and that it remains unclear to what extent pBDNF is key and a reliable biomarker for MDD.     

Increased BDNF levels after electroconvulsive therapy in patients with major depressive disorder: A meta-analysis study

ObjectiveWe performed a systematic review and meta-analysis to estimate brain-derived neurotrophic factor (BDNF) level in patients with major depressive disorder (MDD) after electroconvulsive therapy (ECT).MethodA comprehensive search of the Cochrane Library, MEDLINE, LILACS, Grey literature, and EMBASE was performed for papers published from January 1990 to April 2016. The following key terms were searched: “major depressive disorder”, “unipolar depression”, “brain-derived neurotrophic factor”, and “electroconvulsive therapy”.ResultsA total of 252 citations were identified by the search strategy, and nine studies met the inclusion criteria of the meta-analysis. BDNF levels were increased among patients with MDD after ECT (P value = 0.006). The standardized mean difference was 0.56 (95% CI: 0.17–0.96). Additionally, we found significant heterogeneity between studies (I² = 73%).ConclusionOur findings suggest a potential role of BDNF as a marker of treatment response after ECT in patients with MDD.     

Effects of right unilateral electroconvulsive therapy on motor cortical excitability in depressive patients

Electroconvulsive therapy (ECT) is a widely acknowledged effective treatment for severe major depression. ECT produces considerable anticonvulsant effects that may be related to an increased GABA-ergic neurotransmission. We aimed to explore whether motor cortical excitability as assessed with single and paired pulse transcranial magnetic stimulation (TMS) could be used to investigate these anticonvulsant effects. Therefore, parameters of motor cortical excitability were investigated in 10 patients before and after 10 sessions of right unilateral ECT. After 10 sessions of right unilateral ECT, an enhanced activity of inhibitory circuits in human motor cortex had been observed, as measured by both increased intracortical inhibition and cortical silent period duration, whereas intracortical facilitation and resting motor threshold remained unchanged. The reduction of seizure duration in the course of ECT was associated with clinical improvement and an increase in intracortical inhibition. We interpret this finding as further indirect evidence for changes in inhibitory circuits in the course of ECT in patients with major depression.     

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.     

Factors causing a relapse of major depressive disorders following successful electroconvulsive therapy: A retrospective cohort study

BACKGROUNDElectroconvulsive therapy (ECT) is used to treat major depressive disorder (MDD). Relapse is often observed even after successful ECT, followed by adequate pharmaceutical treatment for MDD. AIMTo investigate the diagnostic factors and treatment strategies associated with depression relapse.METHODSWe analyzed the relationships between relapse, the diagnostic change from MDD to bipolar disorder (BP), and treatment after the initial ECT. We performed a 3-year retrospective study of the prognoses of 85 patients of the Shiga University of Medical Science Hospital. The relative risk of relapse of depressive symptoms was calculated based on the diagnostic change from MDD to BP. A receiver operating characteristic (ROC) curve was generated to evaluate the predictive accuracy of diagnostic changes from MDD to BP based on the duration between the first course of ECT and the relapse of depressive symptoms.RESULTSEighty-five patients initially diagnosed with MDD and successfully treated with ECT were enrolled in the study. Compared with the MDD participants, more BP patients experienced relapses and required continuation and/or maintenance ECT to maintain remission (65.6% vs 15.1%, P < 0.001; relative risk = 4.35, 95%CI: 2.19-8.63, P < 0.001). Twenty-nine patients experienced relapses during the three-year follow-up. In 21 (72.4%, 21/29) patients with relapse, the diagnosis was changed from MDD to BP. The duration from the first course of ECT to relapse was shorter for the BP patients than for the MDD patients (9.63 ± 10.4 mo vs 3.38 ± 3.77 mo, P = 0.022); for most patients, the interval was less than one month. The relative risk of depressive symptoms based on diagnostic changes was 4.35 (95% confidence interval: 2.19–8.63, P < 0.001), and the area under the ROC curve for detecting diagnostic changes based on relapse duration was 0.756 (95%CI: 0.562-0.895, P = 0.007).CONCLUSIONIt may be beneficial to suspect BP and change the treatment strategy from MDD to BP for patients experiencing an early relapse.     

Electroconvulsive therapy (ECT) in a six-year-old girl suffering from major depressive disorder with catatonic features

Objective ECT is generally both effective and safe in the treatment of adolescents, but treatment using ECT in children of pre-pubertal age has been less reported and is a controversial treatment. Clinical picture This article reports a 6-year-old girl who has been diagnosed as having major depressive disorder with catatonic features and 50% loss of weight due to food refusal. Treatment The seven-session ECT treatment with bilateral and brief pulse stimulation was successfully done. Propofol 1% was used for anesthesia. Outcome After the third session, the patient’s clinical improvement began by eating. As the ECT sessions went on the signs of depression and catatonic features completely resolved. There were no noticeable clinical side effects. Conclusion ECT should be considered in severe cases of child psychiatric disorders where it is life threatening, as an effective and safe method.     

重性抑郁障碍的临床特征及其性别差异

目的了解重性抑郁障碍的临床特征及其性别差异。方法采用多阶段分层整群抽样方法随机抽取18周岁及以上的人群10073名,以改编后的一般健康问卷12项（GHQ-12）为筛选工具,以美国精神障碍诊断与统计手册第四版（DSM-IV）轴I障碍定式临床检查患者版（SCID-I/P）为调查的诊断工具。结果重性抑郁障碍的抑郁心境、失眠、疲倦或精力缺乏、兴趣或愉快感缺乏、思考力降低、体重减轻或食欲下降、无价值感、自己死亡的想法、精神运动性激越的出现频率较高;在抑郁发作类型、季节特征、既往发作缓解程度、目前类型、症状严重程度、首次发作年龄及反复发作间歇期的性别比较均无统计学差异。结论重性抑郁障碍各种临床症状的出现频率不同,性别对重性抑郁障碍临床特征的影响有待进一步研究。     

Rapid antidepressant effects of repeated doses of ketamine compared with electroconvulsive therapy in hospitalized patients with major depressive disorder

Accumulating evidence suggests that N-methyl-d-aspartate receptor (NMDAR) antagonists (e.g. ketamine) may exert rapid antidepressant effects in MDD patients. In the present study, we evaluated the rapid antidepressant effects of ketamine compared with the electroconvulsive therapy (ECT) in hospitalized patients with MDD. In this blind, randomized study, 18 patients with DSM-IV MDD were divided into two groups which received either three intravenous infusions of ketamine hydrochloride (0.5 mg/kg over 45 min) or ECT on 3 test days (every 48 h). The primary outcome measure was the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS), which was used to rate overall depressive symptoms at baseline, 24 h after each treatment, 72 h and one week after the last (third) ketamine or ECT. Within 24 h, depressive symptoms significantly improved in subjects receiving the first dose of ketamine compared with ECT group. Compared to baseline level, this improvement remained significant throughout the study. Depressive symptoms after the second dose ketamine was also lower than the second ECT. This study showed that ketamine is as effective as ECT in improving depressive symptoms in MDD patients and have more rapid antidepressant effects compared with the ECT.     

Circadian genes in major depressive disorder

Abstract

Background: Sleep disturbances are a common symptom of major depressive disorder (MDD). Sleep is highly regulated by circadian rhythms, controlled by circadian genes, that act through a series of feedback loops to regulate the sleep-wake cycle.

Objectives: To the best of our knowledge, a systematic review regarding the core circadian genes and their role in MDD has not been published recently. Also, a review of these genes and their role in sleep disturbances in depressed individuals appears to have never been done. We decided to integrate both concepts into one comprehensive review.

Method: The review was done using the appropriate search terms in the following search engines: OVID Medline, Embase, PsycINFO and Pubmed.

Results: Based on the data reviewed, none of the circadian genes appear to be associated with MDD, but some are more promising than others. These genes are: CRY1, CRY2, PER2 and NPAS2. When investigating the role of circadian genes in sleep disturbances among individuals with MDD, the most promising candidate gene is TIMELESS. Although the results in this area are limited.

Conclusion: Given the promising leads from this review, future studies should investigate circadian genes in sleep disturbances among the depressed population.     

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.     

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.     

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。     

Adjunctive atomoxetine for residual fatigue in major depressive disorder

OBJECTIVE: To assess the effectiveness and safety of atomoxetine as an adjunctive medication for residual fatigue in a naturalistic treatment setting. METHODS: A retrospective chart review was conducted to identify major depressive disorder (MDD) patients who had experienced significant symptom improvement (either partial response or remission) following treatment with conventional antidepressants but who were continuing to complain of fatigue. Fourteen such patients (42.2+/-13.4 years of age, five women, baseline HDRS 6.2+/-2.4) with a 17-item Hamilton Depression Rating Scale (HDRS17)<11 who received adjunctive atomoxetine for fatigue were included in the report. Antidepressants augmented were the selective serotonin reuptake inhibitors (SSRIs) (n=11; 78.6%), mirtazapine (n=2, 14.3%), and amitriptyline (n=1, 7.1%). RESULTS: Twelve (85.7%) patients (nine remitters, three partial responders) received at least 4 weeks of atomoxetine treatment. The remaining two (partial responders) discontinued atomoxetine within 1-3 days due to increased anxiety. The brief fatigue inventory (BFI) and Clinical Global Impressions Scale (CGI) were administered when atomoxetine was first prescribed, and following 4-10 weeks of treatment (mean of 5.4+/-1.8 weeks). There was a significant decrease in BFI scores (41.9+/-14.9 versus 24.3+/-13.4, p=0.0015), and HDRS-17 scores (6.2+/-2.4 versus 3.5+/-2.8, p=0.0466), but not CGI-S scores (1.3+/-1.4-1.0+/-0.0, p=0.08) following treatment with atomoxetine. 5/12 (41.6%) patients had a 50% or greater decrease in BFI scores. All 12 patients were remitters at follow-up. The mean atomoxetine dose was 42.8+/-10.6 mg. Side effects included insomnia (n=6), increased anxiety (n=3), nausea (n=1) and dry mouth (n=1). CONCLUSIONS: Although preliminary, these results suggest a possible augmentation role for atomoxetine when used in conjunction with conventional antidepressants for residual fatigue in MDD. Prospective as well as controlled studies are necessary to further explore the role of atomoxetine augmentation in MDD.     

抑郁症的睡眠质量及其相关影响因素

目的了解保定市抑郁症睡眠质量特点及其相关影响因素。方法采用多阶段分层整群抽样方法随机抽取≥18周岁的人群，共10073名，用扩展的一般健康问卷（GHQ-12）将调查对象分为高、中、低危险组，以美国精神障碍诊断与统计手册-第四版（DSM—Ⅳ）轴Ⅰ障碍定式临床检查病人版（SCID—L／P）对调查对象进行抑郁症的诊断。以匹兹堡睡眠质量指数（PSQI）评定睡眠质量。结果8773人完成了TPSQI调查，抑郁症现患125例，睡眠障碍（PSQI总分〉7）的发生比率为68．8％；PSQI总分与有无支持群体、社会环境、教育、职业、住房、经济、卫生保健、法律与犯罪等社会心理与环境问题无相关。结论睡眠障碍是抑郁症的常见症状，受社会心理与环境问题的影响较小。     

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.