Platelet Dynamics in Neurodegenerative Disorders: Investigating the Role of Platelets in Neurological Pathology.

Background: Neurological disorders, particularly those associated with aging, pose significant challenges in early diagnosis and treatment. The identification of specific biomarkers, such as platelets (PLTs), has emerged as a promising strategy for early detection and intervention in neurological health. This systematic review aims to explore the intricate relationship between PLT dynamics and neurological health, focusing on their potential role in cognitive functions and the pathogenesis of cognitive disorders. Methods: Adhering to PRISMA guidelines, a comprehensive search strategy was employed in the PubMed and Scholar databases to identify studies on the role of PLTs in neurological disorders published from 2013 to 2023. The search criteria included studies focusing on PLTs as biomarkers in neurological disorders, their dynamics, and their potential in monitoring disease progression and therapy effectiveness. Results: The systematic review included 104 studies, revealing PLTs as crucial biomarkers in neurocognitive disorders, acting as inflammatory mediators. The findings suggest that PLTs share common features with altered neurons, which could be utilised for monitoring disease progression and evaluating the effectiveness of treatments. PLTs are identified as significant biomarkers for detecting neurological disorders in their early stages and understanding the pathological events leading to neuronal death. Conclusions: The systematic review underscores the critical role of PLTs in neurological disorders, highlighting their potential as biomarkers for the early detection and monitoring of disease progression. However, it also emphasises the need for further research to solidify the use of PLTs in neurological disorders, aiming to enhance early diagnosis and intervention strategies.

Arginine metabolomics in mood disorders.

Alterations of nitric oxide (NO) homeostasis have been described in mood disorders. However, the analytical challenges associated with the direct measurement of NO have prompted the search for alternative biomarkers of NO synthesis. We investigated the published evidence of the association between these alternative biomarkers and mood disorders (depressive disorder or bipolar disorder). Electronic databases were searched from inception to the June 30, 2023. In 20 studies, there was a trend towards significantly higher asymmetric dimethylarginine (ADMA) in mood disorders vs. controls (p = 0.072), and non-significant differences in arginine (p = 0.29), citrulline (p = 0.35), symmetric dimethylarginine (SDMA; p = 0.23), and ornithine (p = 0.42). In subgroup analyses, the SMD for ADMA was significant in bipolar disorder (p < 0.001) and European studies (p = 0.02), the SMDs for SDMA (p = 0.001) and citrulline (p = 0.038) in European studies, and the SMD for ornithine in bipolar disorder (p = 0.007), Asian (p = 0.001) and American studies (p = 0.005), and patients treated with antidepressants (p = 0.029). The abnormal concentrations of ADMA, SDMA, citrulline, and ornithine in subgroups of mood disorders, particularly bipolar disorder, warrant further research to unravel their pathophysiological role and identify novel treatments in this group (The protocol was registered in PROSPERO: CRD42023445962).

Comparative impact of exercise-based interventions for postpartum depression: A Bayesian network meta-analysis.

OBJECTIVE: The current study aimed to address and rank which exercise-based interventions are preferable to standard care/no therapy or another exercise intervention for postpartum depression (PPD) management and provide estimates for future definitive evidence. METHODS: The authors systematically searched PubMed, Embase, the Web of Science, PsycInfo, and ClinicalTrails.gov for randomized controlled trials (RCTs) on exercise-based interventions for PPD from their inception to May 9, 2023. Included were RCTs of exercise-based interventions for PPD with at least 4 weeks' duration. The pooled effects of intervention comparisons were generated by the Bayesian random-effects model, and the quality of evidence was evaluated by the Grading of Recommendations, Assessment, Development, and Evaluations framework. RESULTS: Twelve RCTs (1260 women; mean age, 20-35 years) comparing exercise-based interventions with usual care/no therapy were included. Exercise effectively treats depressive symptoms (standard mean difference [SMD], -0.81 [95% confidence interval (CI), -1.20 to -0.42], P < 0.001). Pram walking was significantly associated with a reduction of depressive symptoms during the postpartum period (SMD, -1.00 [95% CI, -2.60 to -0.10], P = 0.020), as well as yoga (SMD, -0.73 [95% CI, -1.84 to -0.43], P < 0.001) and supervised mixed exercise (SMD, -0.77 [95% CI, -1.67 to -0.01], P = 0.041) compared with usual care/no therapy. In indirect comparisons, pram walking (surface under the cumulative ranking curve, 58.9%) was better than yoga (SMD, -0.28 [95% CI, -1.86 to 1.22], P = 0.322) and supervised mixed exercise (SMD, -0.23 [95% CI, -1.59 to 1.12], P = 0.358). However, the difference was not statistically significant. The confidence in evidence was very low to moderate. CONCLUSION: In women with PPD, all commonly prescribed physical exercises were effective alternative or complementary treatments. However, pram walking may perform better in improving the symptoms of PPD.

Circulating arginine metabolites in Alzheimer's disease and vascular dementia: A systematic review and meta-analysis.

BACKGROUND: Alterations in nitric oxide (NO) synthesis have been reported in Alzheimer's disease and vascular dementia. However, as the measurement of NO in biological samples is analytically challenging, alternative, stable circulatory biomarkers of NO synthesis may be useful to unravel new pathophysiological mechanisms and treatment targets in dementia. METHODS: We conducted a systematic review and meta-analysis of the circulating concentrations of arginine metabolites linked to NO synthesis, arginine, citrulline, asymmetric (ADMA) and symmetric (SDMA) dimethylarginine, and ornithine, in Alzheimer's disease and vascular dementia. We searched for relevant studies in PubMed, Scopus, and Web of Science from inception to the 31st of May 2023. The JBI checklist and GRADE were used to assess the risk of bias and the certainty of evidence, respectively. RESULTS: In 14 selected studies, there were no significant between-group differences in arginine and ornithine concentrations. By contrast, compared to controls, patients with dementia had significantly higher ADMA (standard mean difference, SMD=0.62, 95% CI 0.06-1.19, p = 0.029), SDMA (SMD=0.70, 95% CI 0.34-1.35, p<0.001), and citrulline concentrations (SMD=0.50, 95% CI 0.08-0.91, p = 0.018). In subgroup analysis, the effect size was significantly associated with treatment with cholinesterase inhibitors and/or antipsychotics for ADMA, and underlying disorder (Alzheimer's disease), study continent, and analytical method for citrulline. CONCLUSION: Alterations in ADMA, SDMA, and citrulline, biomarkers of NO synthesis, may be useful to investigate the pathophysiology of different forms of dementia and identify novel therapeutic strategies. (PROSPERO registration number: CRD42023439528).

Age-Related Cognitive Decline, Focus on Microbiome: A Systematic Review and Meta-Analysis.

Aging is a complex process influenced by genetics and the environment, leading to physiological decline and increased susceptibility to diseases. Cognitive decline is a prominent feature of aging, with implications for different neurodegenerative disorders. The gut microbiome has gained attention for its potential impact on health and disease, including cognitive function. This systematic review and meta-analysis aimed to investigate the relationship between the gut microbiome and cognitive function in the context of aging. Following PRISMA guidelines, a comprehensive search strategy was employed in PubMed, Scopus, and Web of Science databases. Studies exploring the role of the microbiome in cognition and neurodegenerative disorders, published between 2013 and 2023, were included. Data extraction and quality assessment were performed. Quantitative synthesis using statistical analyses was performed to examine microbial diversity and relative abundance in various cognitive conditions. Sixteen studies involving a total of 1303 participants were included in the analysis. The gut microbiota's relative abundance was different in individuals with cognitive impairments such as Alzheimer's disease, Parkinson's disease, and dementia, compared to the healthy controls. The most prevalent phyla affected were Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. Meta-analyses indicated substantial heterogeneity among studies focusing on Alzheimer's disease. The overall quality of evidence related to microbial analysis was moderate. The gut microbiome's role in cognitive decline and neurodegenerative disorders warrants investigation. Altered microbial abundance, particularly in specific phyla, is associated with cognitive impairments. However, variations in study findings and methodologies highlight the complexity of the relationship between the gut microbiome and cognitive function. Further studies are needed to better understand the mechanisms underlying this connection and its potential implications for aging and cognitive health.

What is the impact of stress on the onset and anti-thyroid drug therapy in patients with graves' disease: a systematic review and meta-analysis.

BACKGROUND: The effect of stress on Graves' disease (GD) is controversial. Our purpose was to quantify the impacts of stress on patients with Graves' disease. METHODS: Systematic searches of PubMed, MEDLINE, Embase, Web of Science, Scopus, Cochrane Library and PsycInfo were conducted from inception to 1 January 2023. Studies comparing the incidence of stressful life events (SLEs) that occurred before diagnosis and during drug therapy in cases diagnosed with GD and controls were included in the final analysis. RESULTS: Nine case-control studies and four cohort studies enrolling 2892 participants (1685 [58%] patients) were included. Meta-analysis revealed a high and significant effect-size index in a random effect model (d = 1.81, P = 0.01), indicating that stress is an important factor in the onset of GD. The relationship between SLEs and GD was stronger in studies with higher proportions of female patients (ß = 0.22, P < 0.01) and weaker in studies with older patients with GD (ß =-0.62, P < 0.01). However, stress did not significantly affect the outcome of antithyroid drug therapy for GD (d = 0.32, P = 0.09). CONCLUSIONS: The results of this meta-analysis suggest that stress is one of the environmental triggers for the onset of GD. Therefore, we recommend stress management assistance for individuals genetically susceptible to GD, especially for young females.

Paraoxonase/Arylesterase Activity of Serum Paraoxonase-1 and Schizophrenia: A Systematic Review and Meta-Analysis.

The presence of a pro-oxidant state in patients with schizophrenia may account for the increased risk of atherosclerosis and cardiovascular disease in this group and supports the potential utility of circulating biomarkers of oxidative stress for risk stratification and management. We investigated this issue by conducting a systematic review and meta-analysis of the association between the circulating concentrations of paraoxonase-1, an antioxidant calcium-dependent high-density lipoprotein (HDL)-associated esterase, with paraoxonase and arylesterase activity in schizophrenia. We searched electronic databases from inception to 31 May 2023 for studies investigating paraoxonase-1 in patients with schizophrenia and healthy controls and assessed the risk of bias and the certainty of evidence (PROSPERO registration number: CRD42023435442). Thirteen studies were identified for analysis. There were no significant between-group differences in paraoxonase (standard mean difference, SMD = 0.12, 95% CI -0.23 to 0.48, p = 0.50; extremely low certainty of evidence) or arylesterase activity (SMD = -0.08, 95% CI -0.39 to 0.23, p = 0.61; very low certainty of evidence). However, in meta-regression and subgroup analysis we observed significant associations between the SMD of paraoxonase and age (p = 0.003), HDL-cholesterol (p = 0.029), and study country (p = 0.04), and the SMD of arylesterase and age (p = 0.007), body mass index (p = 0.012), HDL-cholesterol (p = 0.002), and pharmacological treatment for schizophrenia (p < 0.001). In the absence of overall between-group differences, our systematic review and meta-analysis suggests that alterations in paraoxonase-1 may reflect a pro-oxidant state in specific subgroups of patients with schizophrenia that require further assessment in appropriately designed studies.

Meta-analysis of peripheral mean platelet volume in patients with mental disorders: Comparisons in depression, anxiety, bipolar disorder, and schizophrenia.

BACKGROUND: There is a growing interest in the role of immune and inflammatory responses in mental disorders (MDs). Mean platelet volume (MPV) is an extensively utilized hemogram parameter that reflects systemic inflammation and immune function. Our research sought to determine whether a connection exists between MPV and various types of MDs. METHODS: We searched PubMed, EMBASE, PsychINFO, and Web of Science for eligible studies from inception to 15 February 2023, supplemented by manual searching the references from relevant articles. We applied standardized mean difference (SMD) and its 95% confidence interval (CI) to estimate the differences in MPV values in patients with MDs compared to controls. RESULTS: We analyzed data from 24 surveys with 4843 participants (2450 patients with MDs and 2393 healthy controls). Two-step meta-analyses were conducted to estimate the SMD in MPV value between individuals with and without MDs. Higher MPV values were substantially linked to MDs (i.e., depression, anxiety, bipolar disorder, and schizophrenia). Moderator and stratified analyses revealed that the aggregate effects were more robust in specific populations, such as younger patients and those who had not taken antipsychotic medication within the previous month. CONCLUSIONS: Our findings corroborate the role of inflammatory response in the pathogenesis of MDs and the pharmacological treatment of these conditions. Regarding the considerable heterogeneity among studies, the level of evidence was very low to moderate.

MicroRNAs, Stem Cells in Bipolar Disorder, and Lithium Therapeutic Approach.

Bipolar disorder (BD) is a severe, chronic, and disabling neuropsychiatric disorder characterized by recurrent mood disturbances (mania/hypomania and depression, with or without mixed features) and a constellation of cognitive, psychomotor, autonomic, and endocrine abnormalities. The etiology of BD is multifactorial, including both biological and epigenetic factors. Recently, microRNAs (miRNAs), a class of epigenetic regulators of gene expression playing a central role in brain development and plasticity, have been related to several neuropsychiatric disorders, including BD. Moreover, an alteration in the number/distribution and differentiation potential of neural stem cells has also been described, significantly affecting brain homeostasis and neuroplasticity. This review aimed to evaluate the most reliable scientific evidence on miRNAs as biomarkers for the diagnosis of BD and assess their implications in response to mood stabilizers, such as lithium. Neural stem cell distribution, regulation, and dysfunction in the etiology of BD are also dissected.