Efficacy of milnacipran on cognitive dysfunction with post-stroke depression: preliminary open-label study

The aim of this study was to assess the therapeutic efficacy of the serotonin norepinephrine reuptake inhibitor (SNRI), milnacipran, on both cognitive impairment and depression in post-stroke depression (PSD) patients. A total of 18 PSD patients, approximately 3 months after stroke, were divided into two groups, milnacipran and control. A total of 10 patients were assigned to the milnaciprane group and eight were assigned to control group. Their cognitive impairment and mood symptoms were measured using the Mini-Mental State Examination (MMSE) and Hamilton Depression Rating Scale (HAM-D) both at the time of admission and at discharge, an interval of approximately 3 months. This study examined the changes in both MMSE and HAM-D scores during the study period. A significant time-by-group interaction for results of the MMSE was observed, although there was no significant difference between the two groups on the HAM-D. Amelioration of cognitive impairment was greater in the milnacipran group than the control group. For PSD patients, milnacipran is effective in improving cognitive dysfunction.     

脑卒中后抑郁患者探究性眼动与事件相关电位的研究

目的观察比较脑卒中后抑郁(PSD)及不伴抑郁脑卒中(NPSD)患者的认知功能差异,评价探究性眼动(EEM)和事件相关电位(ERP)对PSD的临床判定价值。方法对50例PSD及50例NPSD患者以及48名正常对照者分别进行了EEM和ERP测定,并将结果进行比较。结果PSD组EEM和ERP测定的异常率分别为96%(48/50)和92%(46/50),NPSD组分别为86%(43/50)和82%(41/50);PSD和NPSD组EEM测定凝视点(NEF)及反应探索评分(RSS)值均较正常对照组减少,D值增加,差异有统计学意义(P<0.01),两病例组相比,NEF、RSS及D值差异有统计学意义(均P<0.01);PSD和NPSD组ERP测定N2及P3波潜伏期较正常对照组延长,P3波幅降低,差异有统计学意义(均P<0.01),两病例组相比,ERP测定N2及P3波测定结果差异有统计学意义(均P<0.01)。结论PSD患者的认知功能损害较NPSD明显,EEM和ERP测定可作为PSD患者认知功能的判定指标。     

Social isolation,cognitive reserve,and cognition in older people with depression and anxiety

Abstract

Objectives: Poor social connections may be associated with poor cognition in older people who are not experiencing mental health problems, and the trajectory of this association may be moderated by cognitive reserve. However, it is unclear whether this relationship is the same for older people with symptoms of depression and anxiety. This paper aims to explore social relationships and cognitive function in older people with depression and anxiety.

Method: Baseline and two-year follow-up data were analysed from the Cognitive Function and Ageing Study–Wales (CFAS-Wales). We compared levels of social isolation, loneliness, social contact, cognitive function, and cognitive reserve at baseline amongst older people with and without depression or anxiety. Linear regression was used to assess the relationship between isolation and cognition at baseline and two-year follow-up in a subgroup of older people meeting pre-defined criteria for depression or anxiety. A moderation analysis tested for the moderating effect of cognitive reserve.

Results: Older people with depression or anxiety perceived themselves as more isolated and lonely than those without depression or anxiety, despite having an equivalent level of social contact with friends and family. In people with depression or anxiety, social isolation was associated with poor cognitive function at baseline, but not with cognitive change at two-year follow-up. Cognitive reserve did not moderate this association.

Conclusion: Social isolation was associated with poor cognitive function at baseline, but not two-year follow-up. This may be attributed to a reduction in mood-related symptoms at follow-up, linked to improved cognitive function.     

阿替普酶静脉溶栓治疗急性脑梗死后发生卒中后抑郁的影响因素分析

目的分析急性脑梗死(ACI)患者采用阿替普酶静脉溶栓治疗卒中后抑郁(PSD)的发生率和严重程度的影响因素。方法以2015年2月至2017年1月我院收治的符合标准的375例ACI患者为研究对象,按照是否溶栓分为溶栓组(n=190)与非溶栓组(n=185),随访6个月后采用HAMD-17评分判定PSD的发生及严重程度,同时采用自制调查表收集各项临床资料,并对影响因素与PSD的发生及严重程度的相关性进行分析。结果 375例ACI患者中共发生130例PSD;溶栓组47例(轻度27例、中度16例和重度4例),非溶栓组83例(轻度43例、中度28例和重度12例);2组PSD的发生率(χ~2=6.320,P=0.021)及严重程度(Z=-2.151,P=0.032)差异明显。护理人员(r=-2.105,P=0.018)、mRS评分(r=1.810,P=0.018)及是否溶栓(r=-1.866,P=0.012)是PSD发生的影响因素;护理人员(χ~2=14.476,P=0.001)与mRS评分(t=3.876,P=0.000)对PSD严重程度的影响明显;护理人员对非溶栓组PSD严重程度的影响明显(χ~2=6.856,P=0.014);mRS评分对溶栓组(t=2.331,P=0.022)与非溶栓组(t=2.990,P=0.009)PSD严重程度的均有明显影响。结论阿替普酶静脉溶栓可以降低PSD的发生率及严重程度;护理人员(家属)及较低mRS评分是PSD的保护因素。     

Memory and depression in Parkinson's disease

Disorders of learning and memory are a frequent finding in nondemented Parkinson disease (PD) patients. It is not clear to what extent depression, present in at least half the cases of PD, contributes to these disorders. This paper investigates the possible influence of depression on tests of episodic memory in patients with Parkinson's disease (PD). We studied three groups of 11 subjects each (controls, non-depressed PD, mildly to moderately depressed PD). Neuropsychological tests included tests of short and long-term memory in verbal and non-verbal modalities. The two groups of PD patients performed significantly worse than controls on the memory tests, but there were no differences between the depressed and non-depressed PD patients. This lack of influence of depression on neuropsychological performance is compatible with Starkstein's view that cognitive imnpairment is only found beyond a given threshold of depression severity.     

Electroconvulsive therapy and cognitive functions in treatment-resistant depression

Objectives. Electroconvulsive therapy (ECT) is the most effective treatment for drug-resistant depression (DRD). We estimated the short- and long-term effects of ECT on cognitive functions in patients with unipolar and bipolar DRD. Methods. We investigated 63 patients (18 male, 45 female), aged 34–75 years. Cognitive assessments were performed before, immediately after 6–12 ECT sessions, and 3 months thereafter, using the Benton Visual Retention, Trail Making (TMT), Rey-Osterrieth Complex Figure (ROCF) tests, the Digit Span of the Wechsler Adult Intelligence Scale, and the Rey Auditory Verbal Learning (RAVLT), verbal fluency and Stroop tests. Results. Immediately after ECT, a significant worsening was noted in some indices of memory and verbal fluency. However, 3 months after ECT, the indices of both RAVLT and verbal fluency significantly improved compared to baseline, and those of the Benton and ROCF were significantly better than before ECT. The Digit Span, Stroop and TMT were not affected by the treatment. Conclusions. The negative effects of ECT on the reported measures of cognition are transient. After 3 months, the indices of memory were significantly better than before the treatment. In addition to its antidepressant effect in DRD, ECT may also exert a long-term favourable influence on some cognitive functions.     

Post-stroke depression and functional independence: a conundrum

Brown C, Hasson H, Thyselius V, Almborg A‐H. Post‐stroke depression and functional independence: a conundrum.
Acta Neurol Scand: 2012: 126: 45–51.
© 2011 John Wiley & Sons A/S. Objectives – People who suffer a stroke are at risk of developing post‐stroke depression (PSD). Not only does this lower their quality of life but it also increases their risk of another stroke or death. This study aimed to investigate the factors associated with PSD in order to better direct rehabilitation efforts aimed at cutting the incidence of PSD. Material and methods – This study was based on all patients admitted to the stroke unit of a hospital in southern Sweden from 1 October 2003 to 30 November 2005. The total number of patients involved was 181. Measures were collected at 2 ± 1 weeks after discharge from hospital, 3 ± 0.5 months after the occurrence of the stroke and 12 ± 1 months after the occurrence of the stroke. Information collected was results from the Center of Epidemiologic Studies Depression Scale and the Barthel Index together with demographic data including age, sex, time since stroke and relationship status. Results – Those patients involved in the study were mainly men (58–59%) and generally those either married or cohabiting (53–57%). The age of respondents ranged from 32 to 92 years with a mean age of 74.0 (95%CI 72.37–75.63) at 2 ± 1 weeks after discharge. The Barthel Index scores ranged from 15 to 100 with means of between 88.7 and 91.7. Between 15% and 19% of the group were clinically depressed during the time frame of the study. The Barthel Index, measuring functional independence in terms of need for assistance with personal activities of daily living (P‐ADL), was consistently associated with PSD. Conclusions – The differences found in levels of depression between those with lower functional independence after a stroke compared to those more independent in P‐ADL, raise the possibility that attention should be paid to therapeutic rehabilitation for stroke patients to help them recover as much functional independence as possible in order to improve their quality of life and lower their chances of developing PSD.     

Factors associated with post-stroke depression and emotional incontinence: lesion location and coping styles

Post-stroke depression (PSD) and post-stroke emotional incontinence (PSEI) have attracted worldwide interest in recent years. These emotional disturbances have a negative impact on the rehabilitation process and the associated worse outcome. Consequently, defining the risk factors for development of PSD and PSEI is important. In this study, we evaluated 368 consecutive patients with acute ischemic stroke at admission and at three months later. PSD was evaluated by using the Beck Depression Inventory, and PSEI was evaluated using Kim's criteria. The Social Support Rating Scale and Medical Coping Modes Questionnaire were also used as measurement tools. Multivariate analyses showed that anterior cortex infarction was associated with PSEI three months after stroke occurrence. The appearance of PSD was not related to lesion location. Both motor and sensory dysfunctions was independently associated with PSD at admission, whereas low degree of social utilization was the independent factor associated with PSD 3 months after stroke. Acceptance-resignation is related to PSD and PSEI both at admission and 3 months after stroke. Avoidance was the independent factor related to PSD at 3 months after stroke onset.     

Self‐esteem and symptoms of depression in children with seizures: Relationships with neuropsychological functioning and family variables over time

Purpose: To test over time the relationships of neuropsychological functioning to mental health in children following a first recognized seizure and, of primary importance, to determine if the strength of these relationships differs based on risk and protective factors. Methods: In a larger prospective study, 135 children with a first seizure (ages 8–14 years) and 73 healthy sibling controls completed neuropsychological testing at baseline and 36 months. Structured telephone interviews were used to obtain data from children on mental health and family environment; major caregiving parents provided data on demographic and family variables. Data analyses included correlation coefficients and linear regression models. Results: Children with seizures showed an overall trend for improvement in mental health. More children with seizures than siblings had declines in processing speed. Declines in neuropsychological functioning were correlated with worse mental health. With regard to risk and protective factors, higher parent education protected against decline in self‐esteem related to decline in processing speed. Better family functioning and greater parental support protected against decline in self‐esteem related to decrease in verbal memory and learning. Older child age protected against increase in depressive symptoms related to decline in processing speed. Discussion: Seizure onset had a negative impact on mental health in children with declines in cognitive functioning except for older children and those with more family resources. Children should be assessed for declines in processing speed and, if found, those subgroups of children with less educated or more anxious parents and those in less supportive families should be targeted for interventions.     

阿替普酶静脉溶栓与急性脑梗死后卒中后抑郁相关性的研究进展

卒中后抑郁(PSD)是急性脑梗死(ACI)常见并发症。阿替普酶(rt-PA)静脉溶栓是ACI的重要治疗方案。近年来研究表明,rt-PA静脉溶栓与ACI后PSD的发病率及严重程度可能呈负相关。脑及外周血脑源性神经营养因子水平升高、神经功能改善以及“下行反事实思维” 可能是其作用机制。该综述旨在对rt-PA 静脉溶栓与ACI后PSD的相关性及其作用机制进行分析和总结。     

Mild depression in young adults with cerebral infarction at long-term follow-up: A population-based study

We sought to evaluate the prevalence of and risk factors for post-stroke depression (PSD) at long-term follow-up in young adults aged 15-49 years with first-ever cerebral infarction in a population-based study. Scores on Montgomery-Asberg Depression Rating Scale (MADRS) were obtained at follow-up (mean time 6.0 years after the stroke) and analysed in subgroups. MADRS scores were obtained in 196 of 209 surviving patients. PSD (MADRS>or=7) was detected in 56 patients (28.6%). None had severe PSD. Alcoholism (P=0.006), depressive symptoms any time before the index stroke (P=0.016), and severe neurological deficits on admission for the index stroke (P=0.043) were independently associated with PSD. PSD seems milder in young ischaemic stroke patients compared with older patients. Alcoholism, depression any time before the index stroke, and severity of neurological deficits on admission for the stroke increased the risk of developing PSD in the long run.     

Serum interleukin-6 is related to lower cognitive functioning in elderly patients with major depression*

Background: There is an increased evidence of an association between inflammatory mediators, particularly serum IL-6, depression and cognitive impairment in the elderly. This study aims at exploring the relation of peripheral IL-6 to cognitive functions in elderly patients with major depressive disorder (MDD).

Objectives: (1) Assessment of serum IL-6 levels and cognitive functions in elderly patients suffering from major depression and comparing them to healthy age-matched control subjects; (2) correlation between serum IL-6 levels and clinical characteristics of depression and cognitive functions in these patients.

Subjects and methods: The study is an observational, case-control study. It consisted of 80 subjects, 40 with the diagnosis of MDD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM IV-TR) with early onset (first episode before the age of 60) and 40 community-dwelling subjects. They were subjected to the Structured Clinical Interview according to DSM-IV, Montreal Cognitive Assessment, Montgomery Asberg Depression Rating Scale, and serum IL-6 assay using ELISA.

Results: In the depression group, subjects had lower scores in cognitive testing, than the control group (p = 0.001). Serum IL-6 was found to have a negative correlation with cognitive testing in these patients even after controlling for the severity of depressive status and Body Mass Index (BMI) (p = 0.025).

Conclusions: MDD in elderly subjects is associated with decline in cognitive functions that may be related to peripheral IL-6 levels.     

西酞普兰和阿米替林治疗脑卒中后抑郁临床对照观察

目的:比较西酞普兰与阿米替林治疗脑卒中后抑郁的疗效和安全性。方法:41例脑卒中后抑郁患者,随机分两组,分别用西酞普兰和阿米替林治疗6周。采用汉密尔顿抑郁量表(HAMD)、抑郁自评量表(SDS)和副反应量表(TESS)于治疗前和治疗1、2、4、6周末分别评定疗效和不良反应。结果:两组治疗后各周HAMD和SDS评分均较治疗前下降(P均<0.05);其中治疗后1周末,西酞普兰组评分下降较阿米替林组更明显,两组比较差异有显著性(P<0.05),但治疗2~6周末比较,差异均无显著性(P均>0.05);西酞普兰组不良反应较阿米替林组少而轻。结论:西酞普兰治疗脑卒中后抑郁疗效与阿米替林相当,但起效较快,安全性高,不良反应轻微。     

雌激素对脑卒中后抑郁大鼠行为学和神经再生的剂量相关性研究

目的探讨雌激素对脑卒中后抑郁(PSD)大鼠行为学和神经元再生的剂量相关性。方法双侧卵巢切除的SD雌性大鼠,应用大脑中动脉栓塞和慢性不可预见温和刺激的方法建立大鼠PSD模型。将大鼠分为对照组和雌激素不同干预剂量(0μg、1μg、10μg、25μg、100μg)组。雌激素持续干预2周后,观察大鼠行为学改变和侧脑室室下区(SVZ)神经元再生的变化。结果雌激素干预2周后,与雌激素0μg组比较,10μg组和25μg组大鼠的行为学数据有明显改善(P0.05)。免疫组化结果显示,与雌激素0μg组比较,10μg组和25μg组SVZ区神经元数增加明显(分别为P0.01,P0.05)。结论适度生理剂量雌激素可通过增加SVZ神经元改善PSD大鼠的抑郁状态。     

Methylphenidate modulates activity within cognitive neural networks of patients with post-stroke major depression: A placebo-controlled fMRI study

Background

Methylphenidate (MP) is a dopamine- and noradrenaline-enhancing agent beneficial for post-stroke depression (PSD) and stroke recovery due to its therapeutic effects on cognition, motivation, and mood; however, the neural mechanisms underlying its clinical effects remain unknown. This study used functional magnetic resonance imaging (f MRI) to investigate the effect of MP on brain activity in response to cognitive tasks in patients with PSD.

Methods

Nine stroke outpatients with DSM IV defined major depression underwent fMRI during two cognitive tasks (2-back and serial subtraction) on four occasions, on the first and third day of a three-day treatment of MP and placebo. Nine healthy control (HC) subjects matched for age and sex scanned during a single session served as normative data for comparison. The main outcome measure was cognitive task-dependent brain activity.

Results

For the 2-back task, left prefrontal, right parietal, posterior cingulate, and temporal and bilateral cerebellar regions exhibited significantly greater activity during the MP condition relative to placebo. Less activity was detected in rostral prefrontal and left parietal regions. For serial subtraction, greater activity was detected in medial prefrontal, biparietal, bitemporal, posterior cingulate, and bilateral cerebellar regions, as well as thalamus, putamen, and insula. Further, underactivation observed during the placebo condition relative to HC improved or reversed during MP treatment. No significant differences in behavioral measures were found between MP and placebo conditions or between patients and HC.

Conclusions

Short-term MP treatment may improve and normalize activity in cognitive neuronal networks in patients with PSD.     

卒中后抑郁的筛查及相关因素分析

目的 探讨卒中后抑郁的发生率及影响因素.方法 选择2008年7月～2009年4月在天津医科大学总医院神经内科卒中单元收治的158例脑卒中急性期患者为观察对象,登记患者基本信息.发病2w、3m、6m后予HAMD量表评分观察预后.结果 卒中后抑郁在发病14d时发生率为45.6%,3m后50.0%,6m后48.9%,以轻中度抑郁为主,发病6m时重度抑郁出现.女性、年龄在40-50岁之间、文化程度在大专或大专以上、自评性格为内向急躁、月人均收入在500元以下、周工作时间在51-60h有PSD高发趋势,但差异无统计学意义(P＞0.05).结论 卒中后抑郁发生率3m达峰,发病人群随时间变化,女性、年龄在40-50岁之间、高文化程度、自评性格为内向急躁、低收入、高工作强度患者可能有卒中后抑郁高发趋势.     

Brain-derived neurotrophic factor and post-stroke depression

Brain-derived neurotrophic factor (BDNF) is well known to play a critical role in cognition. Its role in mood disorders, including post stroke depression (PSD), is also recognized with more evidence surfacing. In patients with PSD, their serum BNDF level is lower than in those without depression. Furthermore, antidepressants could enhance BDNF expression in the brain, resulting in an alleviation of depression symptoms. Such therapeutic effect can be abolished in animals with the BDNF gene deleted. In PSD patients, the presence of stroke may contribute to the development of depression, including affecting the expression of BDNF. However, the mechanisms of BDNF in the development of PSD remain largely unknown. Lower BDNF levels may have existed in some patients before stroke onset, making them vulnerable to develop depressive symptoms. Meanwhile, the hypoxic environment induced by stroke could possibly downregulate BDNF expression in the brain. Current antidepressant treatments are not specific for PSD and there is a lack of treatments to address the linkage between stroke and PSD. This review summarizes the current knowledge of BDNF in PSD. By regulating BDNF expression, a synergistic effect may be achieved when such treatments are applied together with existing antidepressants.