Prevalence, Severity, and Predictors of Poststroke Depression in a Prospective Cohort of Jordanian Patients

Poststroke depression (PSD) is common and remains a significant risk factor for poor outcomes. This prospective study is aimed at assessing the prevalence, severity, and predictors of PSD among Jordanian stroke survivors. A total of 151 patients who were consequently admitted to a tertiary teaching hospital with ischemic or hemorrhagic strokes were enrolled. Participants were screened on admission for premorbid depression using the PHQ-9 questionnaire; then, screening for PSD was repeated one and three months after stroke using the same tool. Depression prevalence at each screening was reported, and logistic regression analysis was conducted to evaluate for significant predictors. PHQ-9 scores suggestive of depression were reported by 15%, 24.83%, and 17.39% of respondents on admission and after one and three months, respectively. Scores suggesting severe depression were reported by 0.71%, 2.13%, and 6.52% of respondents, respectively. Significant predictors of PSD were having chronic kidney disease, current smoking status, moderate or severe disability (mRS score) at stroke onset, and severe dependence (BI) after one month ( p values 0.007, 0,002, 0.014, and 0.031, respectively). Patients with secondary and high school education levels were less likely to get depression compared with illiterate patients ( p 0.042). This study showed that nearly one in four Jordanian stroke survivors experienced PSD after one month. In contrast, while the overall PSD prevalence declined towards the end of follow-up period, patients who remained depressed showed a tendency towards higher PSD severity.

A Network Meta-Analysis of the Clinical Efficacy and Safety of Commonly Used Chinese Patent Medicines in the Auxiliary Treatment of Poststroke Depression

Background. Poststroke depression (PSD) is a serious complication of clinical cerebrovascular disease. Patients not only have depression-related emotional symptoms but also have physical symptoms, such as autonomic dysfunction. At the same time, patients with varying degrees of depression will delay the neurological function of stroke patients. The recovery time of cognitive function and limb function will increase the risk of accidental death and even aggravate the mortality of cerebrovascular disease. Through combining data analysis and related literature, seven types of Chinese patent medicines (CPMs) widely used in the clinical treatment of PSD have been screened out. These herbs exhibit some clinical comparability under the conditions that the syndrome type and dosage form are relatively uniform. Therefore, in this study, the network meta-analysis method was used to evaluate the safety and efficacy of the seven CPMs screened out, and the probability ranking was performed to screen the best clinical auxiliary treatment plan of CPM. Methods. We searched the Chinese databases, including CNKI, WANFANG, and VIP, as well as the English databases, including the Cochrane Library, EMBASE, and PubMed, from inception to May 31, 2020, to identify randomized controlled trials (RCTs) on seven kinds of CPMs that were the subjects of the clinical research. The bias risk and quality of the included studies were analyzed with the Cochrane Handbook (version 5.1), ADDIS, and R software, and the results were compared in a network meta-analysis (NMA). Results. In terms of clinical effectiveness, the seven kinds of CPMs all improved clinical curative effects, with Jieyu Anshen capsule adjuvant treatment having the most significant effect [odds ratio (OR) = 5.00, 95% CI (1.72–9.48)]. Wuling capsule AT can effectively reduce the score index of scale factors for the HAMD score, NIHSS score, and TESS score [mean difference (MD) = −3.95, 95% CI (−4.88–3.00); OR = −3.25, 95% CI (−5.46)–1.05); OR = 0.22, 95% CI (0.05–0.79), resp.]. Conclusion. The mechanisms of seven CPMs in the adjuvant treatment of PSD have advantages. In terms of safety and efficacy, the CPMs had better clinical adjuvant treatment performance. Although this study concluded that the Jieyu Anshen capsule is the preferred drug for clinical treatment, a clear conclusion still needs to be verified in a high-quality randomized controlled study. In clinical practice, accurate selection and application can be carried out according to the specific characteristics of patients.

The Effect and Mechanism of Exercise Training on Rats with Poststroke Depression Based on the Intestinal Flora

Depression of poststroke depression (PSD) is the most common neuropsychiatric complication after stroke. Patients with PSD had higher mortality, more cognitive disorder, lower quality of life, and higher suicidal tendency. The pathogenesis of PSD mainly involves neurotransmitter inflammatory factors, HPA and BDNF. Enteral dysfunction and intestinal flora disorders caused by stroke can participate in the pathogenesis of PSD through various ways, such as immune, endocrine, and nervous system. In this experiment, we used exercise training as an intervention means to explore the curative effect and possible mechanism by observing the changes of behavior, inflammatory factors, and intestinal flora in rats. The results show that the mechanism of exercise training to improve the depressive behavior of rats may be related to inhibiting the expression of proinflammatory factors and increasing the number of lactic acid bacteria in the intestine.

Lipocalin-2 Regulates Hippocampal Microglial Activation in Poststroke Depression

Background and Purpose: Microglia play important role in poststroke depression (PSD), however, the exact mechanism was still unclear. The purpose of the study was to study the mechanism of microglial activation in PSD.Methods: 24 rats were randomly divided into three groups: the PSD group (n = 10), the poststroke (PS) group (n = 7), and the sham group (n = 7). Primary hippocampal microglia were isolated and cultured, and recombined LCN2 protein was used to stimulate the cultured microglia. The protein expression of Iba1, P38 MAPK and PP38 MAPK was analyzed by western blotting; the LCN2 expression was measured by RT-qPCR, the serum LCN2 level and the NO level were analyzed by ELISA.Results: Open field test scores (horizontal score, vertical score, and self-grooming score) and the serum LCN2 level were significantly decreased in the PSD group compared with the other two groups (P < 0.05). The serum LCN2 level was positively correlated with the horizontal score and negatively correlated with the self-grooming score in the open field test (P < 0.05). The relative protein level of Iba1 and the LCN2 mRNA level were significantly increased in the hippocampal region compared with other brain regions (P < 0.05), while the relative protein level of Iba1 and the LCN2 mRNA level were significantly increased in the PSD group compared with the other two groups (P < 0.05). The length, supernatant NO level, phagocytic ability and migration ability of LCN2-treated microglia were significantly increased compared with those of untreated microglia (P < 0.05). The relative protein levels of P38 MAPK and the PP38 MAPK significantly increased in hippocampal region in the PSD group and LCN2-treated hippocampal microglia (P < 0.05).Conclusion: Hippocampal microglia are activated during PSD; LCN2 may regulate hippocampal microglial activation by the P38 MAPK pathway in the process of PSD.

Is Electroacupuncture an Effective and Safe Treatment for Poststroke Depression? An Updated Systematic Review and Meta-Analysis

Objective. To observe and compare the efficacy and safety of electroacupuncture and antidepressants in the treatment of poststroke depression (PSD) using a meta-analysis method. Methods. The VIP, CNKI, Wanfang, CMB, Embase, PubMed, and Cochrane databases were searched. All randomized controlled trials (RCT) on electroacupuncture treatment of PSD were searched and further screened. Meta-analysis was performed on electroacupuncture and western medicine for PSD to explore the difference in efficacy between electroacupuncture and western medicine for PSD. Results. Nineteen RCTs were included in the meta-analysis. Compared with the Western medicine group, the meta-analysis showed no significant changes in Hamilton Depression Scale (HAMD) scores between the electroacupuncture group and the antidepressant group ( P > 0.05 ). The number of adverse events in the electroacupuncture group was less than that in the antidepressant group. Conclusion. Compared with antidepressants, electroacupuncture is not less effective in improving depression symptoms in PSD patients with greater safety.

Exploring the Mechanism of Action of Herbal Medicine (Gan-Mai-Da-Zao Decoction) for Poststroke Depression Based on Network Pharmacology and Molecular Docking

Background. Poststroke depression (PSD) is the most common and serious neuropsychiatric complication occurring after cerebrovascular accidents, seriously endangering human health while also imposing a heavy burden on society. Nevertheless, it is difficult to control disease progression. Gan-Mai-Da-Zao Decoction (GMDZD) is effective for PSD, but its mechanism of action in PSD is unknown. In this study, we explored the mechanism of action of GMDZD in PSD treatment using network pharmacology and molecular docking. Material and methods. We obtained the active components of all drugs and their targets from the public database TCMSP and published articles. Then, we collected PSD-related targets from the GeneCards and OMIM databases. Cytoscape 3.8.2 was applied to construct PPI and composite target disease networks. In parallel, the DAVID database was used to perform GO and KEGG enrichment analyses to determine the biological processes enriched in the treatment-related drugs in vivo. Finally, molecular docking was used to verify the association between the main active ingredients and their targets. Results. The network pharmacological analysis of GMDZD in PSD revealed 107 active ingredients with important biological effects, including quercetin, luteolin, kaempferol, naringenin, and isorhamnetin. In total, 203 potential targets for the treatment of this disease were screened, including STAT3, JUN, TNF, TPT53, AKT1, and EGFR. These drugs are widely enriched in a series of signaling pathways, such as TNF, HIF-1, and toll-like receptor. Moreover, molecular docking analysis showed that the core active components were tightly bound to their core targets, further confirming their anti-PSD effects. Conclusion. This prospective study was based on the integrated analysis of large data using network pharmacology technology to explore the feasibility of GMDZD for PSD treatment that was successfully validated by molecular docking. It reflects the multicomponent and multitarget characteristics of Chinese medicine and, more importantly, brings hope for the clinical treatment of PSD.

Efficacy and Safety of Chaihu Jia Longgu Muli Decoction in the Treatment of Poststroke Depression: A Systematic Review and Meta-Analysis

Objective. Chaihu Jia Longgu Muli decoction (CLMD) is widely used in the treatment of poststroke depression (PSD) in China. Some evidences show that it has advantages, but there lacks reliable evidence. This study aims to systematically evaluate the efficacy and safety of CLMD in the treatment of PSD. Methods. All randomized controlled trials (RCTs) of CLMD in the treatment of PSD were searched from the following databases: PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, and Chinese Biomedical Literature Service System (CBM), from their inception to May 2021. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies. Meta-analysis was performed using RevMan5.3 software. Results. A total of 13 RCTs involving 1665 patients were finally included in this study, among which 5 RCTs were oral CLMD alone versus antidepressants, and 8 RCTs were oral CLMD with antidepressants versus antidepressants. Meta-analysis results showed that oral administration of CLMD could improve Hamilton’s Depression Scale (HAMD) and the Modified Edinburgh-Scandinavian Stroke Scale (MESSS) scores, improve the Barthel index, and have a low rate of adverse reactions, but there was no significant difference in the total effective rate ( p = 0.21 > 0.05) and the National Institute of Health Stroke Scale (NIHSS) score ( p = 0.47 > 0.05) between the antidepressants group and the oral administration of the CLMD group. Oral CLMD combined with antidepressants could improve the total effective rate, HAMD, and MESSS score, but there was no significant difference in Barthel index ( p = 0.06 > 0.05) and the adverse reaction rate ( p = 0.14 > 0.05) between the two groups. Conclusion. Current evidence suggests that oral CLMD alone or with antidepressants is more effective and safer in the treatment of PSD than oral antidepressants. Due to the limitation of the quality and quantity of the included studies, more high-quality studies are needed to confirm the above conclusion.