Alteration of gut microbiota in post-stroke depression patients with Helicobacter pylori infection.

BACKGROUND: Several studies have identified an association between the gut microbiome and post-stroke depression(PSD), and Helicobacter pylori(H. pylori) infection cause significant alterations in the composition of the gastrointestinal microbiome. However, evidence regarding the role of the H. pylori infection in promoting PSD is still lacking. Here, we conducted a retrospective study to explore risk factors associated with PSD. METHODS: Patients with cerebral infarction were consecutively enrolled from December 2021 to October 2022. The diagnosis of PSD is based on the DSM-V criteria, and the Hamilton Depression Rating Scale(HAMD) was used to identify patients with PSD. White matter lesions were evaluated using magnetic resonance imaging(MRI) and H. pylori infection was detected by 13C-urea breath test. Further, 16S rRNA gene sequencing was used to evaluate the changes in gut microbiota composition of fecal samples from PSD patients. The concentration of short-chain fatty acids(SCFAs) was determined by gas chromatography-mass spectrometry(GC-MS). RESULTS: Multivariate regression analysis showed that deep white matter lesions(DWMLs) [odds ratio(OR) 3.382, 95% confidence interval(CI) 1.756-6.512; P = 0.001] and H. pylori infection(OR 2.186, 95% CI 1.149-4.159; P = 0.017) were the independent risk factors for PSD. Patients with H. pylori infection had more severe depressive symptoms than patients without infection. Intestinal microbiota was significantly different between H. pylori-positive PSD[H. pylori(+)] patients and H. pylori-negative PSD[H. pylori (-)] patients. Fecal SCFAs concentrations were significantly reduced in the H. pylori(+) group compared to the negative ones. CONCLUSION: DWMLs and H. pylori infection may play important roles in the development of PSD. H. pylori infection is likely to be involved in the pathogenesis of PSD by altering the intestinal flora.

Blocking CCR5 activity by maraviroc augmentation in post-stroke depression: a proof-of-concept clinical trial.

BACKGROUND: Post-stroke depression (PSD) is a significant impediment to successful rehabilitation and recovery after a stroke. Current therapeutic options are limited, leaving an unmet demand for specific and effective therapeutic options. Our objective was to investigate the safety of Maraviroc, a CCR5 antagonist, as a possible mechanism-based add-on therapeutic option for PSD in an open-label proof-of-concept clinical trial. METHODS: We conducted a 10-week clinical trial in which ten patients with subcortical and cortical stroke, suffering from PSD. were administered a daily oral dose of 300 mg Maraviroc. Participants were then monitored for an additional eight weeks. The primary outcome measure was serious treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. The secondary outcome measure was a change in the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: Maraviroc was well tolerated, with no reports of serious adverse events or discontinuations due to intolerance. The MADRS scores substantially reduced from baseline to week 10 (mean change: -16.4 ± 9.3; p < 0.001). By the conclusion of the treatment phase, a favorable response was observed in five patients, with four achieving remission. The time to response was relatively short, approximately three weeks. After the cessation of treatment, MADRS scores increased at week 18 by 6.1 ± 9.6 points (p = 0.014). CONCLUSIONS: Our proof-of-concept study suggests that a daily dosage of 300 mg of Maraviroc may represent a well-tolerated and potentially effective pharmacological approach to treating PSD. Further comprehensive placebo-controlled studies are needed to assess the impact of Maraviroc augmentation on PSD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05932550, Retrospectively registered: 28/06/2023.

Depressive Symptoms Moderate the Association Between Functional Level at Admission to Intensive Post-Stroke Rehabilitation and Effectiveness of the Intervention.

INTRODUCTION: Previous studies showed that depression acts as an independent factor in functional recovery after stroke. In a prospective cohort of patients admitted to intensive inpatient rehabilitation after a stroke, we aimed to test depression as a moderator of the relationship between the functional level at admission and the effectiveness of rehabilitation at discharge. METHODS: All patients admitted to within 30 days from an ischemic or hemorrhagic stroke to 4 intensive rehabilitation units were prospectively screened for eligibility to a multicenter prospective observational study. Enrolled patients underwent an evidence-based rehabilitation pathway. We used clinical data collected at admission (T0) and discharge (T1). The outcome was the effectiveness of recovery at T1 on the modified Barthel Index (proportion of achieved over potential functional improvement). Moderation analysis was performed by using the PROCESS macro for SPSS using the bootstrapping procedure. RESULTS: Of 278 evaluated patients, 234 were eligible and consented to enrolment; 81 patients were able to answer to the Hospital Anxiety and Depression Scale (HADS) and were included in this analysis. The relationship between the functional status at admission and rehabilitation effectiveness was significant only in persons with fewer depressive symptoms; depression (HADS cut-off score: 5.9) moderated this relationship (P = .047), independent from age and neurological impairment. CONCLUSIONS: Our results suggest that depression moderates between the functional status at admission and the functional recovery after post-stroke rehabilitation. This approach facilitates the identification of subgroups of individuals who may respond differently to stroke rehabilitation based on depression.

The safety and efficacy of escitalopram and sertraline in post-stroke depression: a randomized controlled trial.

OBJECTIVES: This study aims to evaluate the safety and efficacy of escitalopram and sertraline in post-stroke depression (PSD) patients, to provide more reliable therapeutics for cardiovascular and psychiatric clinical practice. METHODS: We recruited 60 patients (aged 40-89 years old) with an ICD-10 diagnosis of PSD, who were then randomly assigned to two groups and treated with flexible doses of escitalopram (10 to 20 mg/day, n = 30) or sertraline (50 to 200 mg/day, n = 30) for consecutive 8 weeks, respectively. The 24-item Hamilton Depression Rating Scale (HAMD-24), the 14-item Hamilton Anxiety Rating Scale (HAMA-14), the Treatment Emergent Symptom Scale (TESS), the Montreal Cognitive Assessment Scale (MOCA), and the Activity of Daily Living scale (ADL) were used to assess patients before, during, and after treatment for depression, anxiety, adverse effects, cognitive function, and daily living activities. Repeated measures ANOVA, the Mann-Whitney U test, the chi-square test (χ2), or Fisher's exact test was employed to assess baseline demographics, response rate, adverse effects rate, and changes in other clinical variables. RESULTS: Significant reduction in HAMD-24 and HAMA-14 scores was evaluated at baseline, as well as 1, 3, 4, 6, and 8 weeks of drug intervention (p < 0.01). There was a significant group difference in post-treatment HAMD-24 scores (p < 0.05), but no difference was observed in HAMA-14 scores (p > 0.05). Further analysis showed a significant variance in the HAMD-24 scores between the two groups at the end of the first week (p < 0.01). The incidence of adverse effects in both patient groups was mild, but there was a statistically significant difference between the two groups (p < 0.05). The improvement in cognitive function and the recovery of daily living abilities were comparable between both groups (p > 0.05). CONCLUSION: Escitalopram and sertraline showed comparable efficacy for anxiety symptoms, cognitive function, and daily living abilities in PSD patients. In addition, escitalopram was more appropriate for alleviating depressive symptoms. To validate the conclusion, trials with a larger sample size are in demand in the future. The registration number is ChiCTR1800017373.

Factor structure and reliability of the symptom measurement of post-stroke depression in the rehabilitation stage.

BACKGROUND: The incidence of Post Stroke Depression (PSD) in the Rehabilitation Stage is high, which can bring serious physical and psychological disorders to patients. However, there is still a lack of targeted tools for screening PSD in the rehabilitation stage. Therefore, the aim of this study was to evaluate the factor structure and reliability of a measurement instrument to screen for PSD in the rehabilitation stage. METHODS: A cross-sectional study was conducted on 780 hospitalized stroke patients who were within the rehabilitation stage from May to August 2020. Exploratory factor analysis (EFA) as well as first- and second-order confirmatory factor analysis (CFA) were performed to evaluate the factor structure of the newly developed Symptom Measurement of Post-Stroke Depression in the Rehabilitation Stage (SMPSD-RS). The reliability and validity of the SMPSD-RS were also verified using several statistical methods. RESULTS: EFA extracted a 24-item, five-factor (cognition, sleep, behavior, emotion, and obsession) model that can clinically explain the symptoms of PSD during the rehabilitation stage. A first-order CFA confirmed the EFA model with good model fit indices, and the second-order CFA further confirmed the five-factor structure model and showed acceptable model fit indices. Acceptable reliability and validity were also achieved by the corresponding indicators. CONCLUSION: The SMPSD-RS was proven to have a stable factor structure and was confirmed to be reliable and valid for assessing PSD symptoms in stroke patients during the rehabilitation stage.

Clinical application of repetitive transcranial magnetic stimulation in improving functional impairments post-stroke: review of the current evidence and potential challenges.

In recent years, the stroke incidence has been increasing year by year, and the related sequelae after stroke, such as cognitive impairment, motor dysfunction, and post-stroke depression, seriously affect the patient's rehabilitation and daily activities. Repetitive transcranial magnetic stimulation (rTMS), as a safe, non-invasive, and effective new rehabilitation method, has been widely recognized in clinical practice. This article reviews the application and research progress of rTMS in treating different functional impairments (cognitive impairment, motor dysfunction, unilateral spatial neglect, depression) after stroke in recent years, and preliminary summarized the possible mechanisms. It has been found that the key parameters that determine the effectiveness of rTMS in improving post-stroke functional impairments include pulse number, stimulated brain areas, stimulation intensity and frequency, as well as duration. Generally, high-frequency stimulation is used to excite the ipsilateral cerebral cortex, while low-frequency stimulation is used to inhibit the contralateral cerebral cortex, thus achieving a balance of excitability between the two hemispheres. However, the specific mechanisms and the optimal stimulation mode for different functional impairments have not yet reached a consistent conclusion, and more research is needed to explore and clarify the best way to use rTMS. Furthermore, we will identify the issues and challenges in the current research, explore possible mechanisms to deepen understanding of rTMS, propose future research directions, and offer insightful insights for better clinical applications.

Feasibility of Observing Cerebrovascular Disease Phenotypes with Smartphone Monitoring: Study Design Considerations for Real-World Studies.

Accelerated by the adoption of remote monitoring during the COVID-19 pandemic, interest in using digitally captured behavioral data to predict patient outcomes has grown; however, it is unclear how feasible digital phenotyping studies may be in patients with recent ischemic stroke or transient ischemic attack. In this perspective, we present participant feedback and relevant smartphone data metrics suggesting that digital phenotyping of post-stroke depression is feasible. Additionally, we proffer thoughtful considerations for designing feasible real-world study protocols tracking cerebrovascular dysfunction with smartphone sensors.

Fear of disease progression and resilience parallelly mediated the effect of post-stroke fatigue on post-stroke depression: A cross-sectional study.

AIMS: To explore the effect of post-stroke fatigue (PSF) on post-stroke depression (PSD) and examine the mediating effects of fear of disease progression (FOP) and resilience between PSF and PSD. DESIGN: A cross-sectional study. METHODS: A total of 315 stroke patients participated in the questionnaire survey between November 2022 and June 2023. Data were collected using the General Information Questionnaire, Fatigue Severity Scale, Fear of Disease Progression Questionnaire-Short Form, Connor-Davidson Resilience Scale-10 Item and Hospital Anxiety and Depression Scale-Depression Subscale. Data were analysed by descriptive analysis, Mann-Whitney U-test, Kruskal-Wallis H-test, Pearson or Spearman correlation, hierarchical regression analysis and mediation analysis. RESULTS: PSF had a significant positive total effect on PSD (ß = .354, 95% CI: .251, .454). Additionally, FOP and resilience played a partial parallel-mediating role in the relationship between PSF and PSD (ß = .202, 95% CI: .140, .265), and the total indirect effect accounted for 57.06% of the total effect. CONCLUSIONS: FOP and resilience parallelly mediated the effect of PSF on PSD, which may provide a novel perspective for healthcare professionals in preventing PSD. Targeted interventions aiming at reducing PSF, lowering FOP levels and enhancing resilience may be possible ways to alleviate PSD. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Interventions that tail to reducing PSF, lowering FOP levels and enhancing resilience may be considered as possible ways to alleviate PSD. IMPACT: This study enriched the literature by exploring the effect of PSF on PSD and further examining the mediating effects of FOP and resilience between PSF and PSD. Findings emphasized the important effects of PSF, FOP and resilience on PSD. REPORTING METHOD: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cross-sectional studies was used to guide reporting. PATIENT OR PUBLIC CONTRIBUTION: One tertiary hospital assisted participants recruitment.

Exploring the Role of MMP-9 and MMP-9/TIMP-1 Ratio in Subacute Stroke Recovery: A Prospective Observational Study.

Despite the significant changes that unfold during the subacute phase of stroke, few studies have examined recovery abilities during this critical period. As neuroinflammation subsides and tissue degradation diminishes, the processes of neuroplasticity and angiogenesis intensify. An important factor in brain physiology and pathology, particularly neuroplasticity, is matrix metalloproteinase 9 (MMP-9). Its activity is modulated by tissue inhibitors of metalloproteinases (TIMPs), which impede substrate binding and activity by binding to its active sites. Notably, TIMP-1 specifically targets MMP-9 among other matrix metalloproteinases (MMPs). Our present study examines whether MMP-9 may play a beneficial role in psychological functions, particularly in alleviating depressive symptoms and enhancing specific cognitive domains, such as calculation. It appears that improvements in depressive symptoms during rehabilitation were notably linked with baseline MMP-9 plasma levels (r = -0.36, p = 0.025), and particularly so with the ratio of MMP-9 to TIMP-1, indicative of active MMP-9 (r = -0.42, p = 0.008). Furthermore, our findings support previous research demonstrating an inverse relationship between pre-rehabilitation MMP-9 serum levels and post-rehabilitation motor function. Crucially, our study emphasizes a positive correlation between cognition and motor function, highlighting the necessity of integrating both aspects into rehabilitation planning. These findings demonstrate the potential utility of MMP-9 as a prognostic biomarker for delineating recovery trajectories and guiding personalized treatment strategies for stroke patients during the subacute phase.

Cognitive behavioural therapy for depression, quality of life, and cognitive function in the post-stroke period: systematic review and meta-analysis.

The post-stroke period is associated with a lot of sequelae, including depression, decreased quality of life, and decline of cognitive function. Apart from the pharmacotherapy, it is also important to find a non-pharmacological treatment to relieve the sequelae. Cognitive behavioural therapy (CBT) might be a potential candidate, which can be clarified by a systematic review and meta-analysis. The eligible criteria of enrolled studies in the systematic review and meta-analysis were the randomised clinical trials (RCTs) using CBT to treat post-stroke depression, or with the focus on quality of life or cognitive function in the post-stroke period. The endpoint scores of depression, quality of life, and cognitive function scales were the targeted outcome for the final meta-analysis in the random effects model. Ten RCTs with 432 post-stroke patients receiving CBT and 385 controls were included. The meta-analysis results showed significant improvements in depression severity and quality of life. However, no significant difference between CBT and control groups was found in cognitive function. In addition, significant heterogeneity was derived from the meta-analysis. According to the meta-analysis results, CBT might be beneficial for relieving depression severity and improving quality of life. However, cognitive function might not be influenced by CBT. Further studies with a more consistent CBT design with greater sample sizes should be warranted to clarify and confirm the treatment effects of CBT for post-stroke depression and quality of life.

A new perspective on hippocampal synaptic plasticity and post-stroke depression.

Post-stroke depression, a common complication after stroke, severely affects the recovery and quality of life of patients with stroke. Owing to its complex mechanisms, post-stroke depression treatment remains highly challenging. Hippocampal synaptic plasticity is one of the key factors leading to post-stroke depression; however, the precise molecular mechanisms remain unclear. Numerous studies have found that neurotrophic factors, protein kinases and neurotransmitters influence depressive behaviour by modulating hippocampal synaptic plasticity. This review further elaborates on the role of hippocampal synaptic plasticity in post-stroke depression by summarizing recent research and analysing possible molecular mechanisms. Evidence for the correlation between hippocampal mechanisms and post-stroke depression helps to better understand the pathological process of post-stroke depression and improve its treatment.

Comparing the Symptomatology of Post-stroke Depression with Depression in the General Population: A Systematic Review.

Previous research into the phenomenological differences of post-stroke depression (PSD) has typically focused on comparisons of symptom profiles between stroke and non-stroke population controls. This systematic review aimed to synthesize these findings with results from other methodological approaches that contribute to an understanding of phenomenological differences. Articles were identified via a systematic search of seven databases and additional manual searching. A narrative synthesis approach was adopted because of the high methodological heterogeneity. Twelve articles comparing the symptomatology of depression between stroke and non-stroke controls were included. Three distinct methodological approaches, relevant to the aim, were identified: comparisons of profiles among groups with similar overall depression severity, comparisons of the strengths of correlations between a symptom and depression, and comparisons of latent symptom severity. The symptomatology of depression was generally similar between the groups, including somatic symptoms, despite the hypothesized interference of comorbid physical stroke effects. Despite high heterogeneity, there was a tentative indication that post-stroke depression manifests with comparatively less severe/prevalent anhedonia. Possible mechanisms for the observed similarities and differences are explored, including suggestions for future research.

Astrocytes in Post-Stroke Depression: Roles in Inflammation, Neurotransmission, and Neurotrophin Signaling.

Post-stroke depression (PSD) is a frequent and disabling complication of stroke that affects up to one-third of stroke survivors. The pathophysiology of PSD involves multiple mechanisms, including neurochemical, neuroinflammatory, neurotrophic, and neuroplastic changes. Astrocytes are a type of glial cell that is plentiful and adaptable in the central nervous system. They play key roles in various mechanisms by modulating neurotransmission, inflammation, neurogenesis, and synaptic plasticity. This review summarizes the latest evidence of astrocyte involvement in PSD from human and animal studies, focusing on the alterations of astrocyte markers and functions in relation to monoamine neurotransmitters, inflammatory cytokines, brain-derived neurotrophic factor, and glutamate excitotoxicity. We also discuss the potential therapeutic implications of targeting astrocytes for PSD prevention and treatment. Astrocytes could be new candidates for antidepressant medications and other interventions that aim to restore astrocyte homeostasis and function in PSD. Astrocytes could be new candidates for antidepressant medications and other interventions that aim to restore astrocyte homeostasis and function in PSD.

Higher serum lipocalin 2 is associated with post-stroke depression at discharge.

BACKGROUND AND AIMS: Post-stroke depression (PSD), as one of the common complications after stroke, seriously affects the physical and mental health and functional prognosis of patients. Previous studies have shown that the increase of inflammatory mediators is associated with the occurrence of PSD. Lipocalin 2 (LCN2), as an acute phase protein, is involved in the development of acute ischemic stroke (AIS), and its expression is up-regulated in patients with depression, suggesting that there is a potential correlation between serum LCN2 and depression. The aim of this study was to explore the relationship between serum LCN2 at admission and PSD at discharge. METHODS: A total of 358 AIS patients were retrospectively included. All patients had fasting venous blood taken within 24 h of admission to detect serum LCN2. The patients were evaluated by 17-item Hamilton Depression Scale (HAMD) before discharge. Patients with HAMD score > 7 were diagnosed with PSD. The correlation between serum LCN2 and PSD was tested using binary logistic regression analysis. RESULTS: In our study, 92 (25.7%) patients were diagnosed with PSD at discharge. According to the serum LCN2 value, the patients were divided into three layers (Tertile1 ≤ 105.24ng/ml; Tertile2: 105.24-140.12ng/ml; Tertile3 ≥ 140.12ng/ml), with T1 layer (the lowest levels) as a reference, after adjusting for multiple potential confounding factors, T3 layer (the highest levels) was independently associated with the occurrence of PSD (odds ratio [OR] = 2.639, 95% confidence interval [CI]: 1.317-5.287, P = 0.006). Similar results were found when the serum LCN2 was analyzed as a continuous variable. The optimal cut-off value of serum LCN2 at admission to predict PSD at discharge was 117.60ng/ml, at this threshold, the sensitivity was 77.2%, and the specificity was 53.4%. CONCLUSIONS: High serum LCN2 levels at admission are an independent risk factor for PSD in patients with AIS at discharge.

Factors affecting the quality of life after ischemic stroke in young adults: a scoping review.

PURPOSE: To synthesize the body of knowledge on the factors influencing the quality of life (QoL) after ischemic stroke (IS) in young adults. METHODS: Guidelines regarding the scoping review methodology developed by the Joanna Briggs Institute, and the PRISMA-ScR checklist for a scoping review was used in this paper. A total of 1197 studies were identified through a bibliographic search in Web of Science, MEDLINE, PsycInfo, ScienceDirect, Scopus, and ProQuest Science Database. Articles published between the years 2000-2021 were included. RESULTS: A total of nine papers were finally selected to respond to the research question. Three studies were prospective longitudinal studies compared QoL between young stroke and age-matched controls from the general population. Across all the analysed studies, 14 variables potentially associated with QoL were identified. QoL in young patients is mainly affected by clinical outcomes after IS (scored by the modified Rankin scale and the Barthel index-favourable initial functional status and higher independence in ADL leads to higher QoL) and psychological factors (post-stroke fatigue and depression-higher levels of fatigue and depression lead to lower QoL). The reviewed studies emphasized the importance of functional outcomes, post-stroke depression, fatigue and anxiety and early return to work. CONCLUSION: Further longitudinal studies are needed to identify the trajectory of post-stroke psychosocial symptoms over time and other potential predictors of unfavourable long-term QoL, thus specific young stroke rehabilitation and stroke self-management support programmes should be developed (address physical, psychological factors which influence the psychosocial adaptation post-stroke and the perception of the QoL).

Non-invasive brain stimulation for treating post-stroke depression: A network meta-analysis.

OBJECTIVE: To compare the antidepressant effects and tolerability of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) treatments in patients with post-stroke depression (PSD). METHODS: We included randomized controlled trials comparing active stimulation with sham stimulation. Primary outcomes were the depression score after treatment, presented as standardized mean differences with 95% confidence intervals. Response/remission and long-term antidepressant efficacy were also examined. We estimated effect-size using pairwise and Bayesian network meta-analysis (NMA) with random-effects model. RESULTS: We identified 33 studies (total n = 1793). In NMA, 5 of 6 treatment strategies were associated with higher effect compared with sham therapy: dual rTMS (standardized mean differences = -1.5; 95% confidence interval = -2.5 to -0.57), dual LFrTMS (-1.5, -2.4 to -0.61), dual tDCS (-1.1, -1.5 to -0.62), HFrTMS (-1.1, -1.3 to -0.85) and LFrTMS (-0.90, -1.2 to -0.6). And dual rTMS, dual LFrTMS or HFrTMS may be more effective than other interventions for achieving antidepressant effects. Regarding secondary outcomes, rTMS can promote depression remission and response, and alleviate depression for at least 1 month. rTMS and tDCS were well tolerated. CONCLUSIONS: Bilateral rTMS and HFrTMS are considered top-priority non-invasive brain stimulation (NIBS) interventions for improving PSD. Dual tDCS and LFrTMS are also efficient. SIGNIFICANCE: The findings of this study provide evidence for considering NIBS techniques as alternative or add-on treatments for patients with PSD. This work also emphasizes the need for future clinical trials to address the inadequacies identified in this review to optimize methodological quality.

Homocysteine can aggravate depressive like behaviors in a middle cerebral artery occlusion/reperfusion rat model: a possible role for NMDARs-mediated synaptic alterations.

BACKGROUND: Post-stroke depression (PSD), the most frequent psychiatric complication following stroke, could have a negative impact on the recuperation of stroke patients. Hyperhomocysteinemia (HHCY) has been reported to be a modifiable risk factor of stroke. OBJECTIVE: The study tries to explore the effect of HHCY on PSD and the role of N-methyl-d-aspartate receptors (NMDARs)-mediated synaptic alterations. METHODS: Forty-five adult male Sprague-Dawley rats were randomly allocated into five groups: sham operation group, middle cerebral artery occlusion group (MCAO), HCY-treated MCAO group HCY and MK-801 co-treated MCAO group and MK-801-treated MCAO group. 1.6 mg/kg/d D, L-HCY was administered by tail vein injection for 28 d prior to SHAM or MCAO operationand up to 14 d after surgery. The MK-801 (3 mg/kg) was administered by intraperitoneal injection 15 min prior to MCAO operation. RESULTS: HCY treatment aggravated depressive-like disorders of post-stroke rats by the open field test and sucrose preference test. Further, HCY significantly decreased central monoamines levels in the MCAO rats by HPLC. The transmission electron microscopy results showed that the number of synapses and the area of postsynaptic density decreased in the hippocampus of the HCY-treated MCAO rats. Additionally, HCY augmented ischemia-induced up-regulation of NMDARs, decreased the levels of synaptic structure-related marker PSD-95and the synaptic transmission-associated synaptic proteins (VGLUT1, SNAP-25 and Complexin Ι/ΙΙ). These effects of HCY were partly reversed by the NMDA antagonist MK-801. CONCLUSIONS: The current study suggested that NMDARs-mediated synaptic plasticity may be involved in the adverse effect of HCY on PSD.

Acupuncture for post-stroke depression: a systematic review and network meta-analysis.

BACKGROUND: Patients with post-stroke depression (PSD) usually experience anxiety, hopelessness, and insomnia, which have a negative impact on their daily activities and post-stroke rehabilitation. Acupuncture (AC), as a minimally invasive technique, has become a popular choice for improving depression symptoms. However, it is still unclear which therapy is associated with the best outcomes for PSD. In this review, we aimed to explore the impact of AC in alleviating symptoms of PSD and to evaluate the difference in effectiveness between AC combined with pharmacotherapies and various non-pharmacotherapies. METHODS: Six databases and three clinical trials registration platforms were searched from inception to March 2023. Randomized clinical trial comparing needle-based AC with pharmacotherapy, and other non-pharmacotherapy or invalid group were included. Two independent reviewers identified eligible studies, and collected data using a pre-made form. A Bayesian network meta-analysis was conducted to assess and compare different techniques using RStudio 3.6.0 with the package 'GEMTC' V.0.8.1. The primary outcome was the efficacy for PSD assessed by scales measuring depressive symptoms. The secondary outcomes were effectiveness for neurological function and the quality of life. The ranking probabilities for all treatment interventions was performed using the Surface Under the Cumulative Ranking curve (SUCRA). The risk of bias was assessed by using the Revised Cochrane Risk of Bias tool 2. RESULTS: Sixty-two studies, involving 5308 participants published from 2003 to 2022, were included. The results showed that compared with western medicine (WM) (defined as pharmacotherapy for PSD), AC alone or with repetitive transcranial magnetic stimulation (RTMS), Traditional Chinese medicine (TCM) alone or with WM, were superior for alleviating depression symptoms. Compared to Usual Care, AC alone or plus other therapies could significantly decrease scores on the Hamilton Depression Rating scale. According to result of SUCRA, AC plus RTMS had the highest probability of improving depressive symptoms with a probability of 49.43%. CONCLUSIONS: The results of this study indicate that AC alone or combined with other therapies appears to be effective in improving depression symptoms of stroke survivors. Moreover, in comparison to WM, AC alone or plus RTMS, TCM, TCM with WM, or WM, were more effective in improving depression symptoms of PSD. Also, AC with RTMS seems to be the most effective with the highest probability. REGISTRATION: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database in November 2020 and updated in July 2021. The registration number is CRD42020218752.

Psychopathological network for early-onset post-stroke depression symptoms.

BACKGROUND: Post-stroke depression (PSD) can be conceptualized as a complex network where PSD symptoms (PSDS) interact with each other. The neural mechanism of PSD and interactions among PSDS remain to be elucidated. This study aimed to investigate the neuroanatomical substrates of, as well as the interactions between, individual PSDS to better understand the pathogenesis of early-onset PSD. METHODS: A total of 861 first-ever stroke patients admitted within 7 days poststroke were consecutively recruited from three independent hospitals in China. Sociodemographic, clinical and neuroimaging data were collected upon admission. PSDS assessment with Hamilton Depression Rating Scale was performed at 2 weeks after stroke. Thirteen PSDS were included to develop a psychopathological network in which central symptoms (i.e. symptoms most strongly correlated with other PSDS) were identified. Voxel-based lesion-symptom mapping (VLSM) was performed to uncover the lesion locations associated with overall PSDS severity and severities of individual PSDS, in order to test the hypothesis that strategic lesion locations for central symptoms could significantly contribute to higher overall PSDS severity. RESULTS: Depressed mood, Psychiatric anxiety and Loss of interest in work and activities were identified as central PSDS at the early stage of stroke in our relatively stable PSDS network. Lesions in bilateral (especially the right) basal ganglia and capsular regions were found significantly associated with higher overall PSDS severity. Most of the above regions were also correlated with higher severities of 3 central PSDS. The other 10 PSDS could not be mapped to any certain brain region. CONCLUSIONS: There are stable interactions among early-onset PSDS with Depressed mood, Psychiatric anxiety and Loss of interest as central symptoms. The strategic lesion locations for central symptoms may indirectly induce other PSDS via the symptom network, resulting in higher overall PSDS severity. TRIAL REGISTRATION: URL: http://www.chictr.org.cn/enIndex.aspx ; Unique identifier: ChiCTR-ROC-17013993.

Liver function test indices-based prediction model for post-stroke depression: a multicenter, retrospective study.

BACKGROUND: Post-stroke depression (PSD) was one of the most prevalent and serious neuropsychiatric effects after stroke. Nevertheless, the association between liver function test indices and PSD remains elusive, and there is a lack of effective prediction tools. The purpose of this study was to explore the relationship between the liver function test indices and PSD, and construct a prediction model for PSD. METHODS: All patients were selected from seven medical institutions of Chongqing Medical University from 2015 to 2021. Variables including demographic characteristics and liver function test indices were collected from the hospital electronic medical record system. Univariate analysis, least absolute shrinkage and selection operator (LASSO) and logistic regression analysis were used to screen the predictors. Subsequently, logistic regression, random forest (RF), extreme gradient boosting (XGBoost), gradient boosting decision tree (GBDT), categorical boosting (CatBoost) and support vector machine (SVM) were adopted to build the prediction model. Furthermore, a series of evaluation indicators such as area under curve (AUC), sensitivity, specificity, F1 were used to assess the performance of the prediction model. RESULTS: A total of 464 PSD and 1621 stroke patients met the inclusion criteria. Six liver function test items, namely AST, ALT, TBA, TBil, TP, ALB/GLB, were closely associated with PSD, and included for the construction of the prediction model. In the test set, logistic regression model owns the AUC of 0.697. Compared with the other four machine learning models, the GBDT model has the best predictive performance (F1 = 0.498, AUC = 0.761) and was chosen to establish the prediction tool. CONCLUSIONS: The prediction model constructed using these six predictors with GBDT algorithm displayed a promising prediction ability, which could be used for the participating hospital units or individuals by mobile phone or computer.