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Bioenergy decline occurs with reperfusion following acute ischemic stroke. However, the molecular mechanisms that limit energy metabolism and their impact on post-stroke cognitive and emotional complications are still unclear. In the present study, we demonstrate that the p53 transcriptional response is responsible for neuronal adenosine triphosphate (ATP) deficiency and progressively neuropsychiatric disturbances, involving the downregulation of mitochondrial voltage-dependent anion channels (VDACs). Neuronal p53 transactivated the promoter of microRNA-183 (miR-183) cluster, thereby upregulating biogenesis of miR-183-5p (miR-183), miR-96-5p (miR-96), and miR-182-5p. Both miR-183 and miR-96 directly targeted and post-transcriptionally suppressed VDACs. Neuronal ablation of p53 protected against ATP deficiency and neurological deficits, whereas post-stroke rescue of miR-183/VDAC signaling reversed these benefits. Interestingly, cyclin-dependent kinase 9 (CDK9) was found to be enriched in cortical neurons and upregulated the p53-induced transcription of the miR-183 cluster in neurons after ischemia. Post-treatment with the CDK9 inhibitor oroxylin A promoted neuronal ATP production mainly through suppressing the miR-183 cluster/VDAC axis, further improved long-term sensorimotor abilities and spatial memory, and alleviated depressive-like behaviors in mice following stroke. Our findings reveal an intrinsic CDK9/p53/VDAC pathway that drives neuronal bioenergy decline and underlies post-stroke cognitive impairment and depression, thus highlighting the therapeutic potential of oroxylin A for better outcomes.

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Post-stroke depression (POSD) is a common difficulty and most predominant emotional syndrome after stroke often consequences in poor outcomes. In the present investigation, we have designed and studied the neurologically active celastrol/minocycline encapsulated with macrophages-derived exosomes functionalized PLGA nanoformulations (CMC-EXPL) to achieve enhanced anti-inflammatory behaviour and anti-depressant like activity in a Rat model of POSD. The animal model of POSD was established through stimulating process with chronic unpredictable mild stress (CUM) stimulations after procedure of middle cerebral artery occlusion (MCAO). Neuronal functions and Anti-inflammation behaviours were observed by histopathological (H&E) examination and Elisa analyses, respectively. The anti-depressive activity of the nanoformulations treated Rat models were evaluated by open-field and sucrose preference test methods. Microglial polarization was evaluated via flow-cytometry and qRT-PCR observations. The observed results exhibited that prepared nanoformulations reduced the POSD-stimulated depressive-like activities in rat models as well alleviated the neuronal damages and inflammatory responses in the cerebral hippocampus. Importantly, prepared CMC-EXPL nanoformulation effectively prevented the M1 pro-inflammatory polarization and indorsed M2 anti-inflammatory polarization, which indicates iNOS and CD86 levels significantly decreased and upsurged Arg-1 and CD206 levels. CMC-EXPL nanoformulation suggestively augmented anti-depressive activities and functional capability and also alleviated brain inflammation in POSD rats, demonstrating its therapeutic potential for POSD therapy.

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BACKGROUND: Limited observational research has explored the relationship between the non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) ratio (NHHR) and the risk of post-stroke depression (PSD). This study aims to investigate the potential associations between NHHR and PSD. METHODS: A cross-sectional study was conducted using data from stroke participants aged 20 and older, sourced from the National Health and Nutrition Examination Survey (NHANES) spanning 2005 to 2018. Depression was assessed using the PHQ-9 questionnaire. The association between NHHR and PSD risk was evaluated through weighted multivariate logistic regression and restricted cubic spline (RCS) models. Subgroup and sensitivity analyses were performed to validate the findings. RESULTS: In the continuous model, the NHHR value for the PSD group (3.23±1.84) was significantly higher than that of the non-PSD group (2.79±1.40, p=0.015). Logistic regression analysis in the fully adjusted model revealed a positive association between NHHR and PSD (OR 1.16, 95 % CI 1.03-1.30, p=0.016). Interaction tests showed no significant differences across strata (p > 0.05 for interaction). Restricted cubic spline results indicated a linear dose-response relationship between NHHR and PSD risk (P for non-linearity = 0.6). This association persisted in various subgroup analyses. CONCLUSION: NHHR was significantly correlated with an increased risk of PSD among U.S. adults. Further re-search on NHHR could contribute to the prevention and treatment of PSD.

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BACKGROUND: Post-stroke depression (PSD) is closely associated with poor stroke prognosis. However, there are some challenges in identifying and assessing PSD. This study aimed to identify scales for PSD diagnosis, assessment, and follow-up that are straightforward, accurate, efficient, and reproducible. METHODS: A systematic literature search was conducted in 7 electronic databases from January 1985 to December 2023. RESULTS: Thirty-two studies were included, the Patient Health Questionnaire-9 (PHQ-9) and Hamilton Depression Scale (HDRS) had higher diagnostic accuracy for PSD. The sensitivity, specificity, and diagnostic odds ratio of PHQ-9 or diagnosing any depression were 0.82, 0.87, and 29 respectively. And for HDRS, used for diagnosing major depression, the scores were 0.92, 0.89, and 94. Furthermore, these two scales also had higher diagnostic accuracy in assessing depressive symptoms during both the acute and chronic phases of stroke. In patients with post-stroke aphasia and cognitive impairment, highly diagnostic scales have not been identified for assessing depressive symptoms yet. CONCLUSIONS: The PHQ-9 and HDRS scales are recommended to assess PSD. HDRS, which demonstrates high diagnostic performance, can replace structured interviews based on diagnostic criteria.

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OBJECTIVE: Post-stroke depression (PSD) is a prevalent and severe sequela of stroke. It is an emotional disorder that significantly impacts functional recovery, prognosis, secondary stroke risk, and mortality among stroke survivors. The incidence rate of PSD is 18 %∼33 %, with symptoms such as low mood, decreased interest, sleep disorders, decreased appetite, impaired attention, and in severe cases, hallucinations and even suicidal tendencies. While diverse therapeutic modalities are employed globally to address PSD, each approach carries its inherent advantages and limitations. Notably, acupuncture stands out as a promising and effective intervention for ameliorating PSD symptoms and enhancing stroke prognosis. This study aims to conduct a bibliometric analysis to scrutinize the current landscape, identify hotspots, and explore frontiers in acupuncture research for PSD. METHODS: A systematic search for acupuncture and PSD-related research was conducted from January 2014 to October 2023 on the Web of Science Core Collection (WoSCC). The data were downloaded and processed using Bibliometrix and VOSviewer to generate knowledge visualization maps. RESULTS: A total of 11,540 articles related to acupuncture and PSD were retrieved. China emerged as the leading contributor with the highest volume of articles on acupuncture and PSD. Author Liu CZ attained the highest H-index, focusing primarily on investigating the compatibility effects and mechanisms of acupoints. Common hotspot keywords included pain, stimulation, mechanisms, complementary, and alternative medicine. The main research frontiers were mechanisms, neuroinflammation, gut microbiota, and therapeutic methods. CONCLUSION: This study offered multifaceted insights into acupuncture for PSD, unveiling pivotal areas, research hotspots, and emerging trends. The findings aimed to guide researchers in exploring novel research directions and selecting appropriate journals for advancing the understanding and treatment of PSD through acupuncture interventions.

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OBJECTIVE: To conduct the association between vitamin D levels in the acute phase of stroke and post-stroke depression (PSD) in stroke patients. METHODS: Five international databases (PubMed, Web of Science, Embase, Ovid MEDLINE(R), Cochrane Library) and one Chinese database (Wanfang Data) were searched for observational studies in any language reporting on PSD and vitamin D levels tested in the acute phase of stroke in stroke patients from inception to May 2024. Data extraction and study quality assessment were conducted by two authors independently. Qualitative and quantitative analyses of data were performed. The meta-analysis was registered in the PROSPERO database (CRD42023398581). RESULTS: We included 7 studies containing 3537 participants in the systematic review and meta-analysis. All studies that met the inclusion and exclusion criteria were conducted in China. Vitamin D levels in the acute phase of stroke were lower in PSD patients compared with non-PSD patients (weighted mean difference = -14.97 nmol/L; 95% confidence interval = -19.54, -10.40). Stroke patients with vitamin D deficiency (<50 nmol/L) had an increased risk of PSD compared with stroke patients with vitamin D sufficiency (≥75 nmol/L) (odds ratio = 3.59; 95% confidence interval = 2.05, 6.27). However, the association between vitamin D insufficiency (50-75 nmol/L) and PSD were not statistically significant (odds ratio = 4.15; 95% confidence interval = 0.87, 19.78). CONCLUSION: Vitamin D deficiency in the acute phase of stroke may be a risk factor for PSD.

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The aim of this study was to investigate the overall effects of phototherapy on biopterin (BH4), neopterin (BH2), tryptophan (Trp), and behavioral neuroinflammatory reaction in patients with post-stroke depression. There involved a total of 100 hospitalized patients with post-stroke depression at our hospital from February 2021 to December 2022. The participants enrolled were randomly assigned to either the control group or the experimental group. The control group received routine treatment, including medication and psychological support, while the experimental group received 30 min of phototherapy daily for 8 weeks. All participantsvoluntarily participated in the study and provided informed consent. Baseline characteristics of the patients were statistically analyzed. The severity of depressive symptoms was evaluated using the hamilton depression scale (HAMD) and the beck depression inventory (BDI). Levels of amino acid neurotransmitters, including gamma-aminobutyric acid (GABA), aspartic acid (Asp), and glutamic acid (Glu), were measured using radioimmunoassay. Plasma levels of neuroinflammatory factors, such as TNF-α, IL-6, and IL-1ß were, determined using ELISA. Plasma levels of BH4, BH2, and Trp were detected by HPLC. Levels of SOD, GPx, CAT, and MDA in plasma were measured using corresponding kits and colorimetry. Quality of life was assessed using the SF-36 scale. There were no differences in baseline characteristic between the two groups (P > 0.05). The HAMD and BDI scores in the experimental group were lower than those in the control group (P < 0.05), indicating phototherapy could reduce the severity of post-stroke depression. The levels of GABA, Glu, and Asp in both groups significantly increased after treatment compared to their respective levels before treatment (P < 0.01).The levels of GABA in the experimental group were higher than those in the control group (P < 0.01),while the levels of Glu, and Asp were lower than those in the control group (P < 0.01). The plasma levels of TNF-α, IL-6, and IL-1ß in the experimental group were evidently lower than those in the control group (P < 0.05). Moreover, the levels of BH4 and Trp in experimental group were significantly higher than those in the control group (P < 0.05), while the levelsof BH2 in the experimental group were significantly lower than the control group (P < 0.05). Additionally, the levels of SOD, GPx, and CAT in the experimental group were evidently higher than those in the control group (P < 0.05), whereas the levels of MDA in the experimental group were significantly lower than control group (P < 0.05). The experimental group showed higher scores in physical function, mental health, social function, and overall health compared to the control group (P < 0.05). Phototherapy exerted a profound impact on the metabolism of BH4, BH2, and Trp, as well as on behavioral neuroinflammatory reactions and the quality of life in patients suffering from post-stroke depression. Through its ability to optimize the secretion and synthesis of neurotransmitters, phototherapy effectively regulated neuroinflammatory reactions, improved biochemical parameters, enhancedantioxidant capacity, and alleviated depressive symptoms. As a result, phototherapy was considered a valuable adjuvant therapeutic approach for patients with post-stroke depression.

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Background: Post-stroke depression (PSD) is a prevalent psychiatric disorder affecting about one-third of stroke survivors, significantly hindering recovery and quality of life. PSD also imposes a substantial burden on caregivers and healthcare systems. Aromatherapy has shown promise in alleviating depression, anxiety, and sleep disorders. This pilot randomized controlled trial aims to assess the feasibility and preliminary efficacy of mixed herb aromatherapy in treating PSD. Feasibility outcomes encompass recruitment, intervention adherence, assessment completion and safety assessment. Secondary outcomes include evaluations of depression, anxiety, cognitive function, sleep quality, quality of life, and brain function using EEG and fNIRS. Methods: This single-blind pilot randomized controlled trial will be conducted at the Second Rehabilitation Hospital of Shanghai, enrolling ninety-nine post-stroke patients with PSD. Participants will be randomized into three groups: a Non-Active Control Group receiving standardized rehabilitation therapy, a CBT Group receiving conventional rehabilitation with bi-weekly CBT sessions, and an Aromatherapy Group receiving conventional rehabilitation with daily aromatic inhalation sessions. Interventions will last for four weeks, with efficacy assessed at baseline, post-intervention, and one month post-intervention. Rating scales will be used to measure changes in depression, sleep quality, cognitive function, and quality of life. EEG and fNIRS will specifically be used to measure changes in cerebral cortex activity and their correlations with depression. Feasibility will be evaluated through recruitment, intervention adherence, assessment completion and safety assessment. Discussion: This pilot study highlights the potential of mixed herb aromatherapy inhalation for treating PSD, addressing limitations of CBT by promoting self-management. While demonstrating feasibility through recruitment, adherence, assessment completion and safety assessment, the study also acknowledges limitations such as unequal intervention times, the lack of physical function data. And the use of culturally relevant plant powders may enhance compliance but limits generalizability. Despite these constraints, the study provides valuable preliminary data and insights into the mechanisms of aromatherapy, encouraging further research and development of effective PSD treatments.

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Post-stroke depression (PSD) is a prevalent psychiatric disorder after stroke, with the incidence of approximately one-third among stroke survivors. It is classified as an organic mental disorder and has a well-documented association with stroke affecting various aspects of patients, such as the recovery of limb motor function, daily living self-care ability, and increasing the mortality of stroke survivors. However, the pathogenesis of PSD is not yet fully understood. Currently, immune inflammation is a research hotspot. This review focuses on the pathogenesis of PSD, particularly elucidating the role of inflammation in mediating neuroinflammation through innate immunity. Simultaneously, we highlight that peripheral inflammation following a stroke may trigger a detrimental cycle of neuroinflammation by activating innate immune pathways within the central nervous system, which could potentially contribute to the development of PSD. Lastly, we summarize potential treatments for PSD and propose targeting cytokines and innate immune pathways as novel therapeutic approaches.

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ABSTRACTEmotional difficulties are common after stroke and up to one third of stroke-survivors develop post-stroke depression. Psychological distress in this population remains poorly understood, despite high prevalence and secondary implications. One established predictor of depressive symptoms after stroke is cognitive impairment, however, the mechanism underlying this relationship is unclear. This research investigated the potential role of stroke-related illness appraisals as a mediating factor to this known association. Seventy-seven participants, aged 45-94, were consecutively recruited from inpatient stroke units in Oxfordshire over 15-months and completed assessments of mood, cognition and illness appraisals, which were analyzed cross-sectionally. As expected, cognitive impairment significantly predicted depressive symptoms. Importantly, this relationship was shown to be mediated by perceptions of threat and control. Higher levels of cognitive impairment were significantly associated with lower perceived control and higher perceived threat, which partially explained the relationship between cognitive impairment and depressive symptoms. Perceptions of illness coherence were predictive of depressive symptoms but not associated with degree of cognitive impairment. This research has implications for the management of cognitive impairment in the early stages after stroke and suggests that illness appraisals may be an important intervention target for reducing depressive symptoms in patients with post-stroke cognitive impairments.

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BACKGROUND: Depression symptoms are a common complication of stroke and heart disease and is a predictor of Post-stroke depression (PSD). However, the relationship between overall cardiovascular health indicators and PSD remains unclear. METHODS: Data were collected from stroke patients in the 2005-2016 National Health and Nutrition Examination Surveys (NHANES) survey. Depression was defined as a Patient Health Questionnaire-9 (PHQ-9) score ≥10. In addition, PSD was defined as the coexistence of stroke and depression. Life's Simple 7 (LS7) provides an assessment of cardiovascular health and consists of 7 items. The LS7 scores range from 0 to 14 and can also be categorized into poor (0-7), average (8-10), and ideal (11-14). Logistic regression models were used to investigate the relationship between LS7 and PSD. RESULTS: The average age of participants was 64.2 years, with 45.1% and 34.3 % being male and non-Hispanic whites, respectively. After adjusting for age, sex, race, education, and income, the LS7 scores were found to be associated with reduced PSD odds (OR: 0.76, 95% CI: 0.68-0.85, P: <0.001), as well as the number of ideal LS7 metrics (OR: 0.69, 95% CI: 0.56-0.85, P: <0.001). Furthermore, non-poor LS7 was also associated with a lower risk of PSD compared to poor LS7 (OR: 0.48, 95% CI: 0.25-0.91, P: 0.01). This association was stable in stratification analyses. CONCLUSION: Cardiovascular health status assessed by LS7 was negatively associated with PSD. Future studies are required to verify these findings.

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OBJECTIVE: To explore the clinical effect of acupuncture combined with repeated transcranial magnetic stimulation (rTMS) for mild to moderate post-stroke depression. METHODS: Ninety patients with mild to moderate post-stroke depression were randomly divided into a combination group (30 cases, 4 cases dropped out), an acupuncture group (30 cases, 3 cases dropped out) and a rTMS group (30 cases, 5 cases dropped out). All the three groups received basic treatment, the combination group was treated with acupuncture combined with rTMS, the acupuncture group was treated with acupuncture, and the rTMS group was treated with rTMS. The acupuncture was applied at Baihui (GV 20), Yintang (GV 24+) , Danzhong (CV 17) and bilateral Shenmen (HT 7), Taichong (LR 3), Neiguan (PC 6). All the three groups were treated once a day, 5 times a week for 4 weeks. The Hamilton depression scale (HAMD-17) score, Pittsburgh sleep quality index (PSQI) score and event-related potential were compared among the three groups before and after treatment. RESULTS: After treatment, the HAMD-17 scores and PSQI scores in the three groups were reduced compared with those before treatment (P<0.01) , and the HAMD-17 score and PSQI score in the combination group were lower than those in the acupuncture group and the rTMS group (P<0.05). After treatment, the latency of event-related potential (P300, mismatch negativityï¼»MMNï¼½) in the three groups was shortened compared with that before treatment (P<0.05), and the latency of event-related potential in the combination group was shorter than that in the acupuncture group and the rTMS group (P<0.05). CONCLUSION: Acupuncture combined with rTMS can effectively alleviate the depressive state of patients with mild to moderate post-stroke depression, improve the sleep quality and the latency of event-related potential P300 and MMN.

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OBJECTIVE: Post-stroke depression (PSD) is a common neurological and psychiatric sequelae following a stroke, often surpassing the primary effects of the stroke due to its strong correlation with high mortality rates. In recent years, non-pharmacological therapy has garnered significant attention as a supplementary treatment for PSD, becoming widely adopted in clinical practice. However, the efficacy of specific intervention strategies remains unclear. This study aimed to conduct a network meta-analysis (NMA) of published studies to compare the efficacy of different non-pharmacological therapies for treating PSD. METHOD: We systematically searched five databases from inception through March 2024 to identify randomized controlled trials (RCTs) evaluating non-pharmacological therapies for the treatment of PSD. We considered individual intervention and intervention class. Intervention classes included traditional Chinese medicine (TCM), non-invasive electrotherapy stimulation (NIES), psychotherapy (PT), exercise therapy, hyperbaric oxygen, and combined interventions. The NMA was conducted using R and Stata software, following a frequency-based methodology. Assessment of methodological quality and risk of bias was conducted using the Risk of Bias assessment tool 2.0. Therapies were ranked using the P-score, and box-plots visualization, meta-regression, and sensitivity analysis, were performed to assess transitivity, heterogeneity, and consistency, respectively. RESULTS: The NMA included 43 studies with a total of 3138 participants. Random-effects models revealed significant efficacy for acupuncture (ACUP) (P-score = 0.92; pooled standardized mean difference (95% CI): -3.12 (-4.63 to -1.60)) and transcranial direct current stimulation (P-score = 0.85; -2.78 (-5.06 to -0.49)) compared to the treatment as usual (TAU) group. In categorical comparisons, TCM_PT (P-score = 0.82; -1.91 (-3.54 to -0.28)), TCM (P-score = 0.79; -1.65 (-2.33 to -0.97)), and NIES (P-score = 0.74; -1.54 (-2.62 to -0.46)) showed significant differences compared to TAU group. Furthermore, our results indicated no significant difference between PT and the control groups. However, Confidence in Network Meta-Analysis results indicated very low overall evidence grade. CONCLUSION: Limited evidence suggests that ACUP may be the most effective non-pharmacological therapy for improving PSD, and TCM_PT is the best intervention class. However, the evidence quality is very low, underscoring the need for additional high-quality RCTs to validate these findings, particularly given the limited number of RCTs available for each therapy.

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Post-stroke depression is a common complication that imposes significant burdens and challenges on patients. The occurrence of depression is often associated with frontal lobe hemorrhage, however, current understanding of the underlying mechanisms remains limited. Here, the pathogenic mechanisms associated with the circuitry connectivity, electrophysiological alterations, and molecular characteristics are investigated related to the frontal lobe in adult male mice following unilateral injection of blood in the medial prefrontal cortex (mPFC). It is demonstrated that depression is a specific neurological complication in the unilateral hematoma model of the mPFC, and the ventral tegmental area (VTA) shows a higher percentage of connectivity disruption compared to the lateral habenula (LHb) and striatum (STR). Additionally, long-range projections originating from the frontal lobe demonstrate higher damage percentages within the connections between each region and the mPFC. mPFC neurons reveal reduced neuronal excitability and altered synaptic communication. Furthermore, transcriptomic analysis identifies the involvement of the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) signaling pathway, and targeting the JAK-STAT pathway significantly alleviates the severity of depressive symptoms. These findings improve the understanding of post-hemorrhagic depression and may guide the development of efficient treatments.

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Background: Post-stroke depression (PSD) is a well-established psychiatric complication following stroke. Nevertheless, the relationship between early-onset PSD and homocysteine (Hcy) or fibrinogen remains uncertain. Methods: Acute ischemic stroke (AIS) patients who met the established criteria were enrolled in this study. Early-onset PSD was diagnosed two weeks after the stroke. The severity of depressive symptoms was assessed by the Hamilton Depression Scale-17 items (HAMD-17), with patients scored ≥7 assigned to the early-onset PSD group. Spearman rank correlation analysis was employed to evaluate the associations between Hcy, fibrinogen, and HAMD scores across all patients. Logistic regression analysis was conducted to investigate the relationship between Hcy, fibrinogen, and early-onset PSD. Receiver operating characteristic curve (ROC) analysis was ASSDalso performed to detect the predictive ability of Hcy and fibrinogen for early-onset PSD. Results: Among the 380 recruited patients, a total of 106 (27.89%) patients were diagnosed with early-onset PSD. The univariate analysis suggested that patients in the PSD group had a higher admission National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale score (mRS), Hcy, and fibrinogen levels than patients in the non-PSD group (P<0.05). The logistic regression model indicated that Hcy (odds ratio [OR], 1.344; 95% confidence interval [CI] 1.209-1.494, P<0.001) and fibrinogen (OR, 1.57 6; 95% CI 1.302-1.985, P<0.001) were independently related to early-onset PSD. Area under curve (AUC) of Hcy, fibrinogen, and Hcy combined fibrinogen to predict early-onset PSD was 0.754, 0.698, and 0.803, respectively. Conclusion: This study indicates that Hcy and fibrinogen may be independent risk factors for early-onset PSD and can be used as predictive indicators for early-onset PSD.

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Background: Post-stroke depression (PSD) is a frequent complication following a stroke, characterized by prolonged feelings of sadness and loss of interest, which can significantly impede stroke rehabilitation, increase disability, and raise mortality rates. Traditional antidepressants often have significant side effects and poor patient adherence, necessitating the exploration of more suitable treatments for PSD. Previous researchers and our research team have discovered that Botulinum Toxin A (BoNT-A) exhibits antidepressant effects. Therefore, our objective was to assess the efficacy and side effects of BoNT-A treatment in patients with PSD. Methods: A total of 71 stroke patients meeting the inclusion criteria were allocated to the two group. 2 cases were excluded due to severe neurological dysfunction that prevented cooperation and 4 cases were lost follow-up. Ultimately, number of participants in the BoNT-A group (n = 32) and Sertraline group (n = 33). Treatment efficacy was evaluated 1, 2, 4, 8 and 12 weeks post-treatment. Results: There were no significant differences in baseline characteristics between the two groups (p > 0.05). Both groups exhibited comparable treatment efficacy, with fewer side effects observed in the BoNT-A group compared to the Sertraline group. BoNT-A therapy demonstrated significant effects as early as the first week (p < 0.05), and by the 12th week, there was a notable decrease in neuropsychological scores, significantly lower than the baseline level. The analysis revealed significant differences in measurements of the Hamilton Depression Scale (HAMD) (F(770) = 12.547, p = 0.000), Hamilton Anxiety Scale (HAMA) (F(951) = 10.422, p = 0.000), Self-Rating Depression Scale (SDS) (F(1385) = 10.607, p = 0.000), and Self-Rating Anxiety Scale (SAS) (F(1482) = 11.491, p = 0.000). Conclusion: BoNT-A treatment effectively reduces depression symptoms in patients with PSD on a continuous basis.

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BACKGROUND: Previous research showed that behavioural activation is as effective as cognitive-behavioural therapy for general depression. However, it remains unclear if it leads to greater improvement in depressive symptoms when compared with standard treatment for post-stroke depression. AIMS: To compare the effectiveness of behavioural activation against control conditions in reducing depression symptoms in individuals with post-stroke depression. METHOD: This review searched five databases from inception until 13 July 2021 (updated 15 September 2023) for randomised controlled trials comparing behavioural activation and any control conditions for post-stroke depression. Risk of bias was assessed with the Cochrane Collaboration's Risk-of-Bias 2 tool. The primary outcome was improvement in depressive symptoms in individuals with post-stroke depression. We calculated a random-effects, inverse variance weighting meta-analysis. RESULTS: Of 922 initial studies, five randomised controlled trials with 425 participants met the inclusion criteria. Meta-analysis showed that behavioural activation was associated with reduced depressive symptoms in individuals with post-stroke depression at 6-month follow-up (Hedges' g -0.39; 95% CI -0.64 to -0.14). The risk of bias was low for two (40%) of five trials, and the remaining three (60%) trials were rated as having a high risk of bias. Heterogeneity was low, with no indication of inconsistency. CONCLUSIONS: Evidence from this review was too little to confirm the effectiveness of behavioural activation as a useful treatment for post-stroke depression when compared with control conditions. Further high-quality studies are needed to conclusively establish the efficacy of behavioural activation as a treatment option for post-stroke depression.

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Three-needle electroacupuncture (TNEA) has shown promise as a non-pharmacological treatment for post-stroke depression (PSD). However, the underlying mechanisms of its therapeutic effects remain unclear. In this study, we investigated the potential molecular and synaptic mechanisms by which TNEA ameliorates depressive-like behaviors in a mouse model of PSD. Male C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAO) to induce PSD and subsequently treated with TNEA for three weeks at specific acupoints (GV24 and bilateral GB13). Through a combination of behavioral tests, neuronal activation assessment, synaptic function examination, transcriptomic analysis, and various molecular techniques, we found that TNEA treatment significantly improved anxiety and depressive-like behaviors in PSD mice. These improvements were accompanied by enhanced neuronal activation in the medial prefrontal cortex (mPFC) and primary somatosensory cortex (PSC), as well as the promotion of excitatory synapse formation and transmission function in the mPFC. Transcriptomic analysis revealed that TNEA upregulated the expression of Netrin-G Ligand-3 (NGL-3), a postsynaptic cell adhesion molecule, in the mPFC. Further investigation showed that the extracellular domain of NGL-3 binds to the presynaptic protein L1cam, promoting the formation of Vesicular Glutamate Transporter 1 (vGluT1) puncta on neuronal dendrites. Notably, cortical neuron-specific knockout of NGL-3 abolished the antidepressant-like effects of TNEA in PSD mice, confirming the crucial role of the NGL-3/L1cam pathway in mediating the therapeutic effects of TNEA. These findings provide novel insights into the molecular and synaptic mechanisms underlying the therapeutic effects of acupuncture in the treatment of PSD and highlight the potential of targeting the NGL-3/L1cam pathway for the development of alternative interventions for PSD and other depressive disorders.

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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.

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Post-stroke depression (PSD) is a psychological disease that can occur following a stroke and is associated with serious consequences. Research on the pathogenesis and treatment of PSD is still in the infancy stage. Patients with PSD often exhibit gastrointestinal symptoms; therefore the role of gut microbiota in the pathophysiology and potential treatment effects of PSD has become a hot topic of research. In this review, describe the research on the pathogenesis and therapy of PSD. We also describe how the gut microbiota influences neurotransmitters, the endocrine system, energy metabolism, and the immune system. It was proposed that the gut microbiota is involved in the pathogenesis and treatment of PSD through the regulation of neurotransmitter levels, vagal signaling, hypothalamic-pituitary-adrenal axis activation and inhibition, hormone secretion and release, in addition to immunity and inflammation.

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