Development Of Post-stroke Depression Research Articles

The Role Of Fibrosis And Immune Inflammation In Depression In Patients With Ischemic Stroke

Nowadays, Stroke is regarded as the second major cause of death and the third major cause of morbidity globally. The ischemic stroke (IS) is among the most fatal kind of strokes. Thus, due to the importance of this subject, this article aims to analyze the role of fibrosis markers (matrix metalloproteinase-9, tissue inhibitor of matrix metalloproteinases-1), cytokines (tumor necrosis factor-α, interferon-γ, monocytic chemoattractant protein-1) in the development of post-stroke depression in elderly patients with arterial hypertension (AH). To that end, the study included 114 elderly patients with the first acute ischemic stroke; the average age of the patients was 68 ± 7 years. The control group consisted of 20 older people without hypertension and a history of stroke. The level of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) was determined by ELISA (ELISA Kit, USA); the level of tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), monocytic chemoattractant protein-1 (MCP-1) - JSC "Vector-Best", Russia. After 3 months of observation of patients, post-stroke depression (PD) developed in 50 people. (43.8%). Patients who developed PD were significantly older (9.4%, p <0.05), a higher body mass index by 12.2% (p <0.05), a glycemic level by 16.1% (p <0, 05), triglycerides by 14.0% (p <0.05), LDL by 12.8% (p <0.05) than in patients without depression. Patients with ischemic stroke and PD had higher levels of cytokines - TNF-α by 23.8% (p <0.01), INF-γ by 17.5% (p <0.01), MCP-1 by 17, 6% (p <0.01), the level of MMP-9 was higher by 15.3% (p <0.05), TIMP-1 - by 11.4% (p <0.05). Thus, in elderly patients with hypertension with ischemic stroke, the level of fibrosis and inflammation markers may have a prognostic value in developing post-stroke depression. Hence, this article could greatly contribute to the alleviation of depression in patients with ischemic stroke.

Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in Poststroke Depression: A Systematic Review and Meta-Analysis.

Objectives Evidence shows that stroke-induced inflammatory responses play an essential role in the development of poststroke depression (PSD). The goal of this systematic review and meta-analysis was to critically evaluate the literature regarding the use of the neutrophil to lymphocyte ratio (NLR) as a reliable means to detect early PSD development, to help clinicians institute early interventions and improve outcomes. Methods Electronic databases, including Web of Science, PubMed, Google Scholar, and Scopus, were searched, and eight studies were included. We assessed the certainty of the associations with GRADE methods. Results We found that patients with PSD had higher NLR than the stroke patients with no depression (SMD = 0.51; CI 95% = 0.29-0.73, p < 0.001). Also, we found a significantly higher PLR in the patients with PSD when compared to the stroke patients with no depression (SMD = 0.66; CI 95% = 0.19-1.13, p < 0.001). Conclusion These findings indicated that NLR and PLR could be considered inexpensive biomarkers for the prediction of PSD.

Association between C-reactive protein levels and development of post-stroke depression: A systematic review and meta-analysis.

Different prospective cohort studies have focused on the C-reactive protein (ie, a pentameric protein) biomarker as a predictor of post-stroke depression. In this review and meta-analysis, we will attempt to synthesize the evidence for the association between C-reactive protein and the development of post-stroke depression. We systematically searched five academic databases for relevant studies according to the PRISMA guidelines. We evaluate the comparative levels of C-reactive protein in patients with stroke and/without depression, and analyzed the hazard ratio to evaluate the overall risk of C-reactive protein levels in patients with stroke. We selected eligible studies with 2534 patients (mean age: 65.2 ± 5.9 years) from the initial 10 926 studies in the databases. Increased C-reactive protein levels (Hedge's g, 0.84) in patients with stroke and depression as compared to patients with stroke without depression. Increased levels of C-reactive protein were associated with the onset of depression (Hazard's ratio, 1.6) in patients with stroke. Our findings provide an association of C-reactive protein with the development of post-stroke depression, and present higher levels than patients with stroke without depression. Additionally, our findings support the role of C-reactive protein levels as markers for predicting depression in patients with stroke.

Management of Psychiatric Disorders in Patients with Stroke and Traumatic Brain Injury.

Management of Psychiatric Disorders in Patients with Stroke and Traumatic Brain Injury.

High frequency of depressive sympotoms in early phase post-stroke subjects

The development of post-stroke depression (PSD) is the most frequent neuropsychiatric post -stroke complication, with an estimated prevalence between 18 and 33%. This variations occours because of assesment of PSD take place with distinct time intervals from stroke. The diagnosis can be challenging due to the fact several symptoms of depression may overlap with deficits that are a direct consequence of strokes and tools for PSD screeening are not well defined.

Effect of intravenous alteplase on post‐stroke depression in the WAKE UP trial

The aim was to study the effect of intravenous alteplase on the development of post-stroke depression (PSD) in acute stroke patients, and to identify predictors of PSD. This post hoc analysis included patients with unknown onset stroke randomized to treatment with alteplase or placebo in the WAKE-UP trial (ClinicalTrials.gov number, NCT01525290), in whom a composite end-point of PSD was defined as a Beck Depression Inventory ≥10, medication with an antidepressant, or depression recorded as an adverse event. Multiple logistic regression was used to identify predictors of PSD at 90days. Structural equation modelling was applied to assess the indirect effect of thrombolysis on PSD mediated by the modified Rankin Scale. Information on the composite end-point was available for 438 of 503 randomized patients. PSD was present in 96 of 224 (42.9%) patients in the alteplase group and 115 of 214 (53.7%) in the placebo group (odds ratio 0.63; 95% confidence interval 0.43-0.94; p=0.022; adjusted for age and National Institutes of Health Stroke Scale at baseline). Prognostic factors associated with PSD included baseline medication with antidepressants, higher lesion volume, history of depression and assignment to placebo. While 65% of the effect of thrombolysis on PSD were caused directly, 35% were mediated by an improvement of the mRS. Treatment with alteplase in patients with acute stroke resulted in lower rates of depression at 90days, which were only partially explained by reduced functional disability. Predictors of PSD including history and clinical characteristics may help in identifying patients at risk of PSD.

Neuroinflammation and microglia/macrophage phenotype modulate the molecular background of post-stroke depression: A literature review.

Increasing evidence hints to the central role of neuroinflammation in the development of post-stroke depression. Danger signals released in the acute phase of ischemia trigger microglial activation, along with the infiltration of neutrophils and macrophages. The increased secretion of proinflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor α (TNFα) provokes neuronal degeneration and apoptosis, whereas IL-6, interferon γ (IFNγ), and TNFα induce aberrant tryptophane degradation with the accumulation of the end-product quinolinic acid in resident glial cells. This promotes glutamate excitotoxicity via hyperexcitation of N-methyl-D-aspartate receptors and antagonizes 5-hydroxy-tryptamine, reducing synaptic plasticity and neuronal survival, thus favoring depression. In the post-stroke period, CX3CL1 and the CD200-CD200R interaction mediates the activation of glial cells, whereas CCL-2 attracts infiltrating macrophages. CD206 positive cells grant the removal of excessive danger signals; the high number of regulatory T cells, IL-4, IL-10, transforming growth factor β (TGFβ), and intracellular signaling via cAMP response element-binding protein (CREB) support the M2 type differentiation. In favorable conditions, these cells may exert efficient clearance, mediate tissue repair, and might be essential players in the downregulation of molecular pathways that promote post-stroke depression.

Pro-inflammatory cytokines are associated with the development of post-stroke depression in the acute stage of stroke: A meta-analysis

ABSTRACT Background: Pro-inflammatory cytokines may be associated with post-stroke depression (PSD); however, results from different studies are inconsistent. Objectives: To investigate whether pro-inflammatory cytokines are associated with the development of PSD in acute stroke. Methods: PubMed, Embase, and Web of science were searched for relevant literature. Meta-analyzes were performed to determine whether the baseline blood concentrations of pro-inflammatory cytokines differed between acute stroke patients with and without depression. Sensitivity analyzes and regression analyzes were conducted to explore sources of heterogeneity. Results: We included 889 acute stroke patients from eight original studies, 312 of whom developed PSD and 577 did not. The serum concentrations of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were higher in the PSD group, compared with the non-PSD group (IL-6: SMD = 1.26, 95% CI = [0.55, 1.97], P < 0.001; TNF-α: SMD = 0.61, 95% CI = [0.13, 1.10], P = 0.010). Conclusions: This study indicates IL-6 and TNF-α as potential biomarkers of PSD in the acute stage of stroke and provides theoretical support for the early prevention and treatment of PSD.

A Study of Antidepressant Effect and Mechanism on Intranasal Delivery of BDNF-HA2TAT/AAV to Rats with Post-Stroke Depression.

AimPost-stroke depression (PSD) is one of the most frequent neuropsychiatric disorders associated with stroke characterized by depression. The neuroplasticity hypothesis postulates that loss of brain-derived neurotrophic factor (BDNF) plays a major role in pathophysiology of PSD, and restoration of it may represent a critical mechanism underlying antidepressant efficacy.MethodsIn previous studies, we designed a new fusion gene, HA2TAT-BDNF, and cloned it into adenovirus associated virus (AAV) to construct the BDNF-HA2TAT/AAV for the delivery of BDNF to central nervous system (CNS) via nose-brain pathway. In this study, we used it to explore the antidepressant effects on PSD rats through behavioral and various histological methods, and try to find out its specific mechanism.ResultsCompared with the control group, the PSD+AAV group showed decreased sucrose consumption percentage in the sucrose preference test (SPT) (P < 0.001) and prolonged immobility in the forced swimming test (FST) (P=0.000). However, the nasal administration of BDNF-HA2TAT/AAV reversed results of these two behavioral tests (P>0.05, P >0.05), showing an adequate antidepressant effect. Compared with the control group, the concentrations of BDNF mRNA and protein in the hippocampus (P< 0.05, P < 0.01) and prefrontal cortex (P < 0.01, P < 0.01) of PSD rats both decreased. Increased BDNF mRNA and protein expression was observed in the prefrontal cortex (P > 0.05, P < 0.05), without notable change in the hippocampus (P < 0.05, P < 0.001) of PSD+BDNF rats.ConclusionThese results suggest that BDNF reductions in the prefrontal cortex and hippocampus are associated with the development of post-stroke depression, and that increased levels of BDNF in the prefrontal cortex could be used as a therapeutic target to treat PSD. However, the exact mechanism of BDNF action remains unclear in this regard, hindering the wider application of our method. We expect that our research could facilitate the exploration of pathogenesis and the new treatment method of PSD.

Abstract TMP28: Serotonin Transporter Polymorphism Impact on Cortisol Level and Outcome After Stroke

Background: The short (s) allele of a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) is related to reduced serotonin transporter efficiency and an increased vulnerability to stress and mental disorders. The 5-HTTLPR s allele was reported as associate with hypothalamic-pituitary-adrenal (HPA)-axis reactivity to stress, depression and negatively impact on memory. Acute stroke is associated with elevated cortisol levels as part of the body’s reaction to a stress provoking event. We investigated whether 5-HTT genotype interacts with physiological stress to impact on outcome after stroke. Methods: Data from 485 non-depressed cognitively intact first-ever mild to moderate stroke patients from the TABASCO study were available. Patients underwent 3T MRI scans, saliva cortisol measure and comprehensive neuropsychological assessments at admission, 6, and 12 and 24 months thereafter. Results: Carriers of the 5-HTT-s allele (23.2%) had significantly higher admission bedtime salivary cortisol (p=0.042) and more depressive symptoms 12 and 24 months after the index event (p=0.043, p=0.05, respectively) than non-carriers. Higher admission salivary cortisol levels negatively correlated with hippocampal and amigdalar volume at admission (r=-0.257, p=0.004; r=-0.177, p=0.048, respectively) as well as with lower cognitive and higher depression scores 24 months post-stroke (r=-0.2, p=0.032, r=0.245, p=0.007, respectively). The association between salivary cortisol levels, depressive and cognitive scores was stronger in 5-HTT-s carriers than non-carriers. Conclusions: We report that carriers of the 5-HTT-s allele may be at risk to develop depressive symptoms post-stroke. The interactive effects of the s allele and cortisol levels on hippocampal volume and post-stroke depressive symptoms, as well as cognitive performance, suggest that the negative effect of the serotonin polymorphism on the development of post-stroke depression and cognitive decline is mediated by the HPA axis. Since genetic factors may influence vulnerability to the adverse effects of stress, serotonin receptors may provide a novel target for therapeutics to prevent depression and cognitive deterioration in stroke patients.

Imaging markers associated with the development of post-stroke depression and apathy: Results of the Cognition and Affect after Stroke - a Prospective Evaluation of Risks study.

IntroductionIt has been suggested that the development of post-stroke apathy (PSA) and depression (PSD) may be more strongly associated with generalised brain pathology, rather than the stroke lesion itself. The present study aimed to investigate associations between imaging markers of lesion-related and generalised brain pathology and the development of PSA and PSD during a one-year follow-up.Patients and methodsIn a prospective cohort study, 188 stroke patients received 3-Tesla MRI at baseline (three months post-stroke) for evaluation of lesion-related, vascular, and degenerative brain pathology. Presence of lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces was summed to provide a measure of total cerebral small vessel disease (cSVD) burden (range 0–4). The Mini International Neuropsychiatric Interview and Apathy Evaluation Scale were administered at baseline and repeated at 6- and 12-month follow-up to define presence of PSD and PSA, respectively.ResultsPopulation-averaged logistic regression models showed that global brain atrophy and severe cSVD burden (score 3–4) were significantly associated with the odds of having PSA (ORGEE 5.33, 95% CI 1.99–14.25 and 3.04, 95% CI 1.20–7.69, respectively), independent of stroke lesion volume and co-morbid PSD. Medium cSVD burden (score 2) was significantly associated with the odds of having PSD (ORGEE 2.92, 95% CI 1.09–7.78), independent of stroke lesion volume, co-morbid PSA, and pre-stroke depression. No associations were found with lesion-related markers.ConclusionsThe results suggest that generalised degenerative and vascular brain pathology, rather than lesion-related pathology, is an important predictor for the development of PSA, and less strongly for PSD.

Effect of Inflammation on the Process of Stroke Rehabilitation and Poststroke Depression.

A considerable body of evidence has shown that inflammation plays an important role in the process of stroke rehabilitation and development of poststroke depression (PSD). However, the specific molecular and cellular mechanisms involved remain unclear. In this review, we summarize how neuroinflammation affects stroke rehabilitation and PSD. We mainly focus on the immune/inflammatory response, involving astrocytes, microglia, monocyte-derived macrophages, cytokines (tumor necrosis factor alpha, interleukin 1), and microRNAs (microRNA-124, microRNA 133b). This review provides new insights into the effect of inflammation on the process of stroke rehabilitation and PSD and potentially offer new therapeutic targets of stroke and PSD.

Risk factors for post-stroke depression in Sohag University Hospital

BackgroundDepression is one of the important complications of stroke. Post-stroke depression is associated with more physical disability, especially in daily activities, poor functional outcome, and high mortality rate.ObjectiveOur study aimed to investigate the risk factors for development of post-stroke depression 3 months following stroke.MethodsThis is a comparative study, comparing stroke patients with and without depression 3 months after the onset. Hamilton Depression Rating Scale (HDRS), Mini-Mental State Examination (MMSE), Scandinavian Stroke Scale (SSS), and modified Rankin scale (mRS) were used to evaluate patients 3 months post-stroke for depression, cognition, and physical disability. The patients were divided into two groups: patients’ group with depression and patients’ group without depression according to DSM-IV criteria. The clinical characteristics and scores on the HDRS, MMSE, SSS, and mRS were compared between depressive group and non-depressive group. Logistic regression analysis was performed to identify risk factors for depression 3 months after stroke.ResultsA total 102 stroke patients were recruited. Of these, 62 patients (60.78%) had depression. Multivariate logistic regression indicated that smoking, hypertension, increased physical disability, and impaired cognitive function were associated with post-stroke depression.ConclusionImportant risk factors found for PSD included smoking, hypertension, increased physical disability, and impaired cognitive function.

Роль нейротрофических факторов в развитии постинсультной депрессии

Роль нейротрофических факторов в развитии постинсультной депрессии

The association between serum BDNF levels with post-stroke depression and anxiety: A cohort study

Brain-derived neurotrophic factor (BDNF) has been shown to play an important role in psychological function. The aim of this study was to investigate the association of serum BDNF and development of post-stroke depression and anxiety. Serum concentration of BDNF was measured in stroke patients on admission to inpatient rehabilitation hospital. Depression and anxiety mood was diagnosed using (Diagnostic and Statistical Manual of Mental Disorders 4th edition [DSM-IV] criteria). The functional outcome was measured using Functional Independent measures (FIM). Post-stroke depression was diagnosed in 61 (37.7%) patients and anxiety was diagnosed in 40 (24.7%) patients. Except for marital status ( P = 0.030) and BDNF levels ( P = 0.033), none of the predictor variables showed statistically significant differences among the three groups. Low level of BDNF was significantly associated with post-stroke depression ( P = 0.009, OR: 0.93, 95% CI: 0.88–0.98), but not with PSA ( P = 0.469, OR: 0.98, 95% CI: 0.93–1.04). In addition, BDNF level was associated FIM motor scores at discharge in this cohort patients ( P = 0.027,OR: 0.036–0.602, B: 0.319). Low BDNF levels were found to be important risk factors for PSD but not for PSA.

Relationship between serum vitamin D levels and inflammatory markers in acute stroke patients.

IntroductionLow serum vitamin D levels are associated with the development of poststroke depression (PSD). Inflammatory markers play an important role in pathophysiology of PSD. The relationship between vitamin D levels and inflammatory markers has been discussed in nonstroke individuals. The purposes of this study were to explore the relationship between vitamin D levels and inflammatory markers in acute stroke patients and examine the effect of vitamin D and inflammatory markers on PSD.MethodsA total of 152 acute stroke patients were recruited. Serum levels of 25‐hydroxyvitamin D and inflammatory markers were measured by standardized laboratory methods. Depression symptoms were assessed with the 17‐item Hamilton Depression Scale (HAMD‐17). Patients with the HAMD‐17 scores ≥7 were identified to have depression symptoms.ResultsSerum vitamin D levels were negatively correlated with serum levels of interleukin‐6 and high‐sensitivity C‐reactive protein (hsCRP) (r = −.244, p = .002; r = −.231, p = .004). Multiple regression analysis showed that interleukin‐6 and hsCRP levels were associated with vitamin D levels (B = −0.355, p = .003; B = −2.085, p = .006), whereas age, height, weight, leukocyte count, neutrophil ratio, and lymphocyte rate could be omitted without changing the results. In multivariate analyses, the serum levels of vitamin D and interleukin‐6 were associated with the development of PSD after adjusted possible variables (OR = 0.976, 95% CI: 0.958–0.994, p = .009; OR = 1.029, 95% CI: 1.003–1.055, p = .027).ConclusionsSerum vitamin D levels are inversely associated with the levels of interleukin‐6 and hsCRP, suggesting a potential anti‐inflammatory role for vitamin D in stroke individuals.

Decreased Serum Brain-Derived Neurotrophic Factor May Indicate the Development of Poststroke Depression in Patients with Acute Ischemic Stroke: A Meta-Analysis

Depression is a common complication after stroke and has been associated with poor outcome. Thus, it is of great importance to identify potential biomarkers that can aid in predicting and detecting patients with stroke at high risk of poststroke depression (PSD) development. Previous studies showed that brain-derived neurotrophic factor (BDNF) had potential use as a biomarker for discriminating patients with stroke at high risk of PSD. However, the results were inconsistent. A meta-analysis was performed to evaluate the correlation between the peripheral BDNF levels and the development of PSD in the acute stage of stroke. Data were obtained from 4 studies including 499 patients with stroke. Among them, 171 patients were diagnosed with PSD at follow-ups. Our results showed that patients with stroke who were predisposed to developing PSD had significantly lower serum BDNF concentrations at the early stage of stroke. This study suggests a potential association between circulating BDNF concentrations at admission and subsequent PSD development, and provides additional support for the involvement of BDNF in the PSD development.

Proton Magnetic Resonance Spectroscopy Study on the Metabolism Changes of Cerebellum in Patients with Post-Stroke Depression

Objective: To study the metabolic changes of cerebellum by proton magnetic resonance Spectroscopy (¹H-MRS) and discuss the relationships between the cerebellar changes and depression severity in patients with post-stroke depression. Methods and Results: Data of demographic characteristics, individual history and life style of all subjects were collected. 40 patients with stroke and 20 controls were enrolled. All groups received T1WI, T2WI, DWI and ¹H-MRS examination. The cerebral infarction volume and the distribution and severity of leukoaraiosis were evaluated. The ratios of NAA/Cr, Cho/Cr and Cho/NAA in the cerebellum were calculated. There were no statistical significant difference in the NAA/Cr, Cho/Cr and Cho/NAA ratios in bilateral cerebellum between CONT group and NORM group. The Cho/Cr and Cho/NAA ratios in the cerebellum contralateral to the stroke region were higher in PSD group than those in NORM and CONT groups, and the Cho/Cr and Cho/NAA ratios in the cerebellum ipsilateral to the stroke region were similar with those in NORM and CONT groups. However, there were no statistical significant difference in the NAA/Cr ratios in bilateral cerebellum among three groups. Conclusion: The result shows preliminarily that the cerebellum involves in the development of post-stroke depression.

Effects of interleukin-6, interleukin-18, and statin use, evaluated at acute stroke, on post-stroke depression during 1-year follow-up

Proinflammatory cytokines are associated with the development of post-stroke depression (PSD). Statins are thought to possess anti-inflammatory properties but their interactions with cytokines regarding the risk of PSD have yet to be investigated. Thus, the present study aimed to determine whether interleukin (IL)-6 and IL-18 were associated with the development of depression at 2 weeks and 1year after stroke using a longitudinal post-stroke cohort. Furthermore, this study examined the potential interactions between statin use and cytokines on PSD. For this study, 286 patients were evaluated 2 weeks after stroke and 222 patients were followed-up 1year later. Depression was diagnosed using criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) and then categorized into no PSD or any PSD, which included diagnoses of both major and minor depression. The effects of IL-6 and IL-18 on PSD as well as their interaction with a statin at both examination time-points were investigated using a multivariate logistic regression model. Higher IL-6 and IL-18 levels were independently associated with depressive disorders within 2 weeks and at 1year after stroke. When stratified by statin use, these significant associations were more evident in patients who did not use a statin. Furthermore, there was a significant interaction between statin use and IL-6 on the presence of a depressive disorder at 1year. The present findings support the cytokine hypothesis of PSD and indicate that the preventive effects of statin use against PSD may be mediated by its interactions with IL-6.

Role of hypothalamic cannabinoid receptors in post-stroke depression in rats.

One of the most common psychological consequences of stroke is post-stroke depression (PSD). While more than 30 percent of stroke patients eventually develop PSD, the neurobiological mechanisms underlying such a phenomenon have not been well investigated. Given the critical involvement of hypothalamic-pituitary-adrenal axis and endocannabinoid system in response to stressful stimuli, we evaluated the hypothesis that cannabinoid receptors in the hypothalamus are critical for modulation of post-stroke depression-like behaviors in rats. To this end, rats were treated with middle cerebral artery occlusion (MCAO) followed by chronic unpredictable mild stress (CUMS) treatment procedure. We then assessed the expression of CB1 and CB2 receptors in the hypothalamus, and evaluated the effects of pharmacological stimulations of CB1 or CB2 receptors on the expression and development of depression-like behaviors in PSD rats. We found that PSD rats exhibited decreased the expression of CB1 receptor, but not CB2 receptor, in the ventral medial hypothalamus (VMH). Such an effect was not observed in the dorsally adjacent brain regions. Furthermore, intra-VMH injections of CB2 receptor agonist, but not CB1 receptor agonist, attenuated the expression of depression-like behaviors in PSD rats. Finally, repeated intraperitoneal injections of CB1 or CB2 receptor agonists during CUMS treatment inhibited the development of depression-like behaviors in PSD rats. Taken together, these results suggest that decreased CB1 receptor expression is likely associated with the development of post-stroke depression, and CB2 receptor may be a potential therapeutic target for the treatment post-stroke depressive disorders.