Effects of IL-6/IL-6R axis alterations in serum, plasma and cerebrospinal fluid with the schizophrenia: an updated review and meta-analysis of 58 studies.

Studies investigating the association between IL-6/IL-6R axis and schizophrenia (SZ) susceptibility found inconsistent data. To reconcile the results, a systematic review followed by a meta-analysis was performed to assess the associations. This study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search of the literature was carried out in July 2022 using electronic databases PubMed, EBSCO, Science Direct, PsychInfo, and Scopus. Study quality was assessed by the Newcastle-Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effect or random-effect model analysis. Fifty-eight studies were identified, including 4,200 SZ patients and 4,531 controls. Our meta-analysis results showed an increase of IL-6 levels in plasma, serum, or CSF and decreased IL-6R levels in serum in patients under treatment. Further studies are needed to better elucidate the correlation between the IL-6/IL-6R axis and the schizophrenia.

Effect of risperidone on serum IL-6 levels in individuals with schizophrenia: a systematic review and meta-analysis.

BACKGROUND: Risperidone has been significant correlated with a direct effect of interleukin-6 (IL-6) levels in patients with schizophrenia. This fact allows the opportunity to link the probable immunomodulatory effect of antipsychotic medication. Specially, a proper functioning of IL-6 pathway plays a potential role in the treatment or development of schizophrenia. OBJECTIVE: Our primary aim was to perform a systematic review and meta-analysis to determine the effect of risperidone on IL-6 levels in individuals with schizophrenia. METHODS: Studies were identified through a systematic search using PubMed, Scopus, and Web of Science databases. The articles found were subjected to the inclusion and exclusion criteria; then, the mean and standardised differences were extracted to calculate the standardised mean differences using the CMA software. RESULTS: IL-6 levels in individuals with schizophrenia were compared before and after receiving risperidone as treatment. Increased levels of IL-6 levels were observed in individuals with schizophrenia who received risperidone (point estimate 0.249, lower limit 0.042, upper limit 0.455, p-value 0.018). In the Asian population sub-analysis, no statistically significant differences were observed (point estimate 0.103, lower limit -0.187, upper limit 0.215, p value 0.890). When we compared individuals with schizophrenia to the control groups, a significant increase of IL-6 levels was observed in the group with schizophrenia (point estimate 0.248, lower limit 0.024, upper limit 0.472, p-value 0.30). CONCLUSIONS: Risperidone appears to play an important role in IL-6 levels in schizophrenia. Potential implications of increased IL-6 levels in people with schizophrenia should be considered in future studies.KEY POINTSIncreased levels of IL-6 levels were observed in individuals with schizophrenia who received risperidone.Risperidone appears to play an important role in IL-6 levels in schizophrenia.This study could serve for future research focussed on IL-6.

High Serum Levels of IL-6 Are Associated with Suicide Attempt but Not with High Lethality Suicide Attempts: A Preliminary Case-Control Study.

Suicide attempts are an emerging health problem around the world. Increased levels of IL-6 have been associated with suicidal behavior. Therefore, the aims of this study were to evaluate the serum levels of IL-6 in individuals with suicide attempts and a comparison group and to associate the IL-6 levels with the lethality of the suicide attempt. Additionally, we associated the rs2228145 polymorphism of the IL6R gene with suicide attempts or with the IL-6 serum levels. Suicide attempts and their lethality were evaluated using the Columbia Suicide Severity Rating Scale. The serum concentrations of IL-6 were measured by the ELISA technique in individuals with suicide attempts and then compared to a control group. The rs2228145 polymorphism of the IL6R gene was analyzed by real-time polymerase chain reaction. We found elevated serum levels of IL-6 in the suicide attempt group when compared to the control group (F = 10.37, p = 0.002). However, we found no differences of the IL-6 levels between high and low lethality. The IL6R gene polymorphism rs2479409 was not associated with suicide attempts. Our data suggest that IL-6 serum is increased in individuals with suicide attempts.

Cannabis smoking increases the risk of suicide ideation and suicide attempt in young individuals of 11-21 years: A systematic review and meta-analysis.

BACKGROUND: Cannabis is the most frequently consumed drug around the world. Its use has been associated with increased suicide behaviors; nonetheless, the association of cannabis smoking and suicide behaviors in adolescents has not yet been established. The aim of this systematic review and meta-analysis was to evaluate the risk of suicide attempt, suicidal ideation or suicide planning in individuals of 11-21 years of age who smoke cannabis. METHODS: We performed an online searched using PubMed, EBSCO and Science Direct databases, up to July 2021. We calculated odds ratio with 95% confidence intervals to evaluate the association between suicide attempt, suicidal ideation or suicide planning and cannabis smoking in individuals of 11-21 years of age. RESULTS: Twenty studies reported suicide attempts in 34,859 young individuals, suicidal ideation in 26, 937 individuals, and suicide planning in 9054 young individuals. We found an increased risk of suicide attempt in cannabis smokers than in non-cannabis users (OR: 2.33; 95% CI: 1.78-3.05; Z p value; <0.0001; I2 = 97.12%), as well as a significant association between cannabis smoking and suicidal ideation (OR: 2.04; 95%CI: 1.64-2.53; Z p value: <0.001; I2: 94.88) and suicide planning (OR: 1.674; 95% CI: 1.554-1.804; Z p value: 0.000; I2: 92.609). Subgroup analyses showed that American teens have an increased risk of suicidal ideation; the meta-regression analysis revealed that age was negatively associated with the risk of suicide attempt. CONCLUSIONS: This meta-analysis shows that cannabis smoking increased the risk of suicide attempt, suicidal ideation and suicide planning in young individuals of 11-21 years of age. The high risk of suicide behaviors could vary depending on the population studied; therefore, more studies are necessary to corroborate the risk of presenting suicide behaviors in individuals of 11-21 years of age who smoke cannabis.

Fluoxetine modulates the pro-inflammatory process of IL-6, IL-1ß and TNF-α levels in individuals with depression: a systematic review and meta-analysis.

Clinical evidence suggests that inflammation is a key factor to understand the causes of depressive symptoms. Fluoxetine is one of the main first-line medications used for depression, and it is hypothesized that it participates in the decrease of pro-inflammatory cytokines. Hence, our aim was to perform a meta-analysis and systematic review to understand the interaction of fluoxetine in the IL-1ß, IL-6 and TNF-α inflammatory process. Studies identified in PubMed and Scopus databases were used to perform a meta-analysis via the Comprehensive software. Standardized mean difference (SMD) was used as a summary statistic. The analysis included a total of 292 individuals with major depressive disorder who received fluoxetine for a period longer than 6 weeks; additionally, IL-1ß, IL-6 or TNF-α levels were measured at the end of the antidepressant treatment. The findings were significant revealed decreased levels of the cytokines studied. In conclusion, the pooled data suggest that fluoxetine treatment improved depressive symptomatology by the modulation of pro-inflammatory process such as IL-1ß, IL-6 or TNF-α.

Interleukin-6 Levels in Serum, Plasma, and Cerebral Spinal Fluid in Individuals with Suicide Behavior: Systematic Review and Meta-Analysis with Meta-Regression.

Evidence suggests that interleukin-6 (IL-6) concentrations have an important role in suicide behavior (SB) as they are usually increased in these individuals, although no conclusive outcomes have been attained. The purpose of this study was to evaluate the IL-6 levels in plasma, serum, and cerebral spinal fluid (CSF) to determine through a meta-analysis if these levels are increased in individuals with SB in comparison to a group. We calculated the standardized mean difference and 95% confidence intervals (95% CIs). In the systematic review, 21 studies were included, while in the meta-analysis, we included nine studies. The results of our meta-analysis indicated that individuals with SB had reduced levels of IL-6 in plasma (d - 0.189, 95% CI: -0.274 to -0.103, Z, P (Q) = 0.339, I2= 7.478), but increased levels of IL-6 in serum (d - 1.14, 95% CI: 0.658 to 1.630, Z, P (Q) = 0.26, I2= 7.47) and CSF (d 0.64, 95% CI: 0.245 to 1.035, Z, P (Q) = 0.163, I2= 44.80). The meta-regression analysis showed an association between males and high IL-6 levels in plasma (P = 0.003) and serum (P = 0.010), but not the central nervous system (CNS), while age was not associated with IL-6 levels in any of the samples evaluated (plasma, serum, or CNS). The present meta-analysis indicates that serum and CNS IL-6 levels are increased in individuals with SB, while plasma IL-6 levels are decreased, highlighting the importance of the biological sample at the moment of selecting IL-6 as biomarker. However, we need more studies performed in different populations that measure IL-6 and also consider gender when these measures are performed.

Genome-wide association study of psychiatric and substance use comorbidity in Mexican individuals.

The combination of substance use and psychiatric disorders is one of the most common comorbidities. The objective of this study was to perform a genome-wide association study of this comorbidity (Com), substance use alone (Subs), and psychiatric symptomatology alone (Psych) in the Mexican population. The study included 3914 individuals of Mexican descent. Genotyping was carried out using the PsychArray microarray and genome-wide correlations were calculated. Genome-wide associations were analyzed using multiple logistic models, polygenic risk scores (PRSs) were evaluated using multinomial models, and vertical pleiotropy was evaluated by generalized summary-data-based Mendelian randomization. Brain DNA methylation quantitative loci (brain meQTL) were also evaluated in the prefrontal cortex. Genome-wide correlation and vertical pleiotropy were found between all traits. No genome-wide association signals were found, but 64 single-nucleotide polymorphism (SNPs) reached nominal associations (p < 5.00e-05). The SNPs associated with each trait were independent, and the individuals with high PRSs had a higher prevalence of tobacco and alcohol use. In the multinomial models all of the PRSs (Subs-PRS, Com-PRS, and Psych-PRS) were associated with all of the traits. Brain meQTL of the Subs-associated SNPs had an effect on the genes enriched in insulin signaling pathway, and that of the Psych-associated SNPs had an effect on the Fc gamma receptor phagocytosis pathway.

Genetic Polymorphisms of CCDC26 rs891835, rs6470745, and rs55705857 in Glioma Risk: A Systematic Review and Meta-analysis.

A genetic component is accepted in the etiology of the glioma. Evidence from candidate genes studies and GWAS reveal that CCDC26 gene could increase the risk of glioma. We performed a systematic review and up-to-date meta-analysis to explore if polymorphisms of CCDC26 gene (rs891835, rs6470745, and rs55705857) may be a susceptibility factor in developing glioma. An online search in PubMed, Web of Science, and SCOPUS up to September 2018 was performed. The pooled odds ratios were evaluated by fixed effects model and random effects model. Analyses of the overall sample and ethnic sub-groups were performed. In all the analyses, the allelic, additive, dominant, and recessive models were used. We found an association between all polymorphisms evaluated and an increased risk for glioma in the overall population in all the models studied. In sub-group analysis, we found that rs891835 and rs6470745 increased the risk of glioma in Europeans and Caucasians. On the other hand, the rs891835 polymorphism did not reveal any statistical association in Chinese population. Taken into consideration the limitations of this study, the present findings suggest a possible participation of rs891835, rs6470745, and rs55705857 as risk factors to develop glioma. Furthermore, it is possible that the involvement of CCDC26 variants depends on ethnicity. However, we recommend to perform further studies to have conclusive outcomes.

Prolotherapy for knee osteoarthritis using hypertonic dextrose vs other interventional treatments: systematic review of clinical trials

Abstract Background: To evaluate the efficacy and safety of prolotherapy with hypertonic dextrose in patients with knee osteoarthritis. A systematic search was performed in electronic databases including PUBMED, SCIELO, DIALNET and Google Scholar. Main body: We searched for randomized clinical trials that evaluated therapeutic interventions in patients with knee osteoarthritis. These trials compared the effect of intra-articular and / or extra-articular infiltrations of hypertonic dextrose vs the effect of intra-articular and / or extra-articular infiltrations of other substances or some interventional procedure application, via assessing pain, physical function and secondary effects and / or adverse reactions. Ten randomized clinical trials were included in this systematic review, the total sample size comprised 328 patients treated with hypertonic dextrose (prolotherapy) vs 348 controls treated with other infiltrations such as local anesthetics, hyaluronic acid, ozone, platelet-rich plasma or interventional procedures like radiofrequency. Conclusions: In terms of pain reduction and function improvement, prolotherapy with hypertonic dextrose was more effective than infiltrations with local anesthetics, as effective as infiltrations with hyaluronic acid, ozone or radiofrequency and less effective than PRP and erythropoietin, with beneficial effect in the short, medium and long term. In addition, no side effects or serious adverse reactions were reported in patients treated with hypertonic dextrose. Although HDP seems to be a promising interventional treatment for knee OA, more studies with better methodological quality and low risk of bias are needed to confirm the efficacy and safety of this intervention.

Lack of Association of Coffee Consumption with the Prevalence of Self-Reported Type 2 Diabetes Mellitus in a Mexican Population: A Cross-Sectional Study.

It is estimated that almost 366 million people are currently suffering from diabetes mellitus worldwide. However, it has been suggested that coffee consumption has a protective effect against the development of type 2 diabetes mellitus. This association has been observed in many regions around the world. Today, there are no reports in Mexico regarding this association. Therefore, the aim of this study was to assess the association between coffee intake and self-reported type 2 diabetes mellitus in the southeastern part of Mexico. This study included 1277 residents of Comalcalco, a municipality of Tabasco State, Mexico. We calculated the prevalence for diabetes and performed multivariate analysis using multiple logistic regressions to evaluate the combined association with type 2 diabetes mellitus. The prevalence of the diabetes was 12.52% (95% CI: 10.67⁻14.38). The majority of people surveyed (77.29%; 95% CI: 74.95⁻79.60) indicated they were coffee drinkers. The results of multivariate analysis showed a non-significant relationship between the number of cups of coffee drank and type 2 diabetes mellitus. The adjusted odds ratio gave the following values: 1.20, (95% CI: 0.59⁻2.41) for non-daily consumption; 1.66 (0.82⁻3.34), for 1 cup of coffee peer day, and 1.49 (0.78⁻2.86) for 2⁻3 cups. Subsequently, an adjustment was made for age, gender, marital status, education, alcohol consumption, and cigarette smoking. In our population, we did not observe an association between coffee intake and its protective relationship with self-reported type 2 diabetes mellitus.

Evaluación psicológica de la agresividad impulsiva/predeterminada y factores asociados: Un estudio transversal en usuarios de los servicios de salud en Tabasco, México / Psychological evaluation of impulsive/premeditated aggression and associated factors: a cross-sectional study in users of health services in Tabasco, Mexico

Resumen: INTRODUCCIÓN: La conducta suicida es un problema de salud pública. Se sugiere que la personalidad impulsiva o predeterminada participa en los actos de agresividad como el suicidio. OBJETIVO: En este estudio se identificaron diferencias sociodemográficas, de intento de suicidio y la presencia de depresión entre individuos con característica de agresividad impulsiva o predeterminada. MÉTODOS: Se realizó un estudio de tipo transversal que incluyó a 200 residentes de Villahermosa, Tab., México, usuarios de los servicios de salud en ese Estado. La agresividad predeterminada o impulsiva se caracterizó usando la Escala de Agresión Impulsiva/Predeterminada (IPAS). Las características sociodemográficas, de intento de suicidio y de depresión fueron divididas de acuerdo al tipo de agresividad. Subsecuentemente fueron comparadas las características entre los dos grupos. RESULTADOS: Los resultados psicológicos revelaron que la agresividad impulsiva está presente en 62.71 % de la población. Estar desempleado y ser mujer fueron asociadas con la agresividad predeterminada. De igual forma, la mayor proporción de personas con depresión se observó en el grupo de personas predeterminadas (x2 = 18.29, gl = 1, p = 0.001). La proporción de personas con por lo menos un intento de suicidio a lo largo de la vida es similar en las impulsivas y las predeterminadas (6.06% y 6.30%, respectivamente). DISCUSIÓN Y CONCLUSIÓN: El presente estudio no muestra relación entre la personalidad y la proporción del intento de suicidio en los usuarios de los servicios de salud en Tabasco. Sin embargo, el estado de ánimo podría estar asociado con la toma de decisiones.

Abstract: INTRODUCTION: Suicidal behaviour is a public health problem. It has been suggested that impulsive or premeditated personality interferes with aggressive acts such as suicide. OBJECTIVE: In this study, we identified the socio-demographic differences when attempting suicide, as well as the concomitant depression among individuals characterized by impulsive or premeditated aggression. METHODS: We performed a transversal study that included 200 residents of Villahermosa, Tabasco, Mexico, who regularly use the city's General Health Services. The premeditated or impulsive aggression was evaluated using the Impulsive/Premeditated Aggression scale (IPAS). The sample was divided in two groups: impulsive and premeditator individuals. Suicidal attempt, presence of depression and socio-demographic characteristics were evaluated after wards and compared between groups. RESULTS: The psychological evaluation revealed that impulsive aggression is present in 62.71% of the population. We observed that being unemployed and/or being a woman were characteristics associated with premeditated aggression. The premeditators group had the higher proportion of concomitant depression (x2 = 18.29, gl = 1, p = 0.001). The proportion of people that had attempted suicide at least once during their lives was similar in both groups (impulsive = 6.06%, premeditators = 6.30%). DISCUSSION AND CONCLUSION: This study does not show any association between the personality (impulsive or premeditative) and the frequency of suicide attempts in the Tabascan General Health Services users. Nevertheless, the frame of mind (depression) could be associated with taking decisions when attempting suicide.

Association between CRP and TNF-α genes Variants and Cardiovascular Heart Disease in a Mexican Population: Protocol for a Case-Control Study.

BACKGROUND: The C-reactive protein (CRP) and the tumor necrosis factor-alpha (TNF-α) are considered markers of inflammation and have been shown to predict the risk of incident cardiovascular events. However, few studies have undertaken a comprehensive examination of SNPs (single nucleotide polymorphisms) of the CRP and TNF-α genes; due to this, we will present a protocol study to evaluate the role of the CRP and TNF-α genes in Mexican individuals. METHODS/DESIGN: we will perform a case-control study to explore the CRP and TNF-α genotype distribution as well as the serum influence of rs1800947, rs1130864, rs2794521 and rs1205 (polymorphisms of the CRP gene) and rs361525, rs1800629, rs1799724, rs1800630, rs1799964 (of the TNF-α gene) in Mexican individuals who present coronary artery disease. ETHICS AND DISSEMINATION: a written informed consent will be obtained from all the participating subjects. An article detailing the results of the study will be submitted for publication in an international peer-reviewed journal, in accordance with STROBE criteria.

Association of G308A and G238A Polymorphisms of the TNF-α Gene with Risk of Coronary Heart Disease: Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: It is widely acknowledged that coronary heart disease (CHD) has a genetic influence. One of the most promising candidate genes is tumor necrosis factor-alpha (TNF-α). Although there have been several positive studies associating the TNF-α gene and CHD, the evidence is not entirely consistent. The aim of the study was to evaluate the role of the TNF-α gene in CHD using combined evidence by generating a meta-analysis and a systematic review of all published data. METHODS: Meta-analysis and systematic review were conducted using 27 articles of genetic association studies of the TNF-α gene variants (G308A and G238A) and CHD. To analyze the association we used allelic, additive, dominant and recessive models. Moreover, we conducted a subanalysis by populations using the same four models. RESULTS: TNF-α variant G308A showed a significant association with CHD but only when the analysis comprised the whole population. In addition, the variant G238A yielded the same outcome in the Asian population. CONCLUSIONS: Genetic polymorphisms at positions -308 and -238 in the promoter region of the TNF-α gene may be useful as predictive factors for CHD.

The role of gene variants of the inflammatory markers CRP and TNF-α in cardiovascular heart disease: systematic review and meta-analysis.

It is widely acknowledged that cardiovascular heart disease (CHD) has a genetic influence. Several studies have investigated the role of inflammatory markers like C-reactive protein (CRP) and tumor necrosis factor α (TNF-α) in the causation of cardiovascular diseases. Although there have been several positive studies associating CRP and TNF-α genes with CHD, the evidence is not entirely consistent. Therefore, we performed a meta-analysis to gain a better understanding into this issue. The meta-analysis was conducted with 22 articles of genetic association studies of CRP (G1059C rs1800947, C1444T rs1130864, C717T rs2794521 and G3872A rs1205) and TNF-α (C857T rs1799724, C863A rs1800630 and T1031C rs1799964) genes. To analyze the association of these variants with CHD we used the following models: allelic, additive, dominant and recessive. In addition, we performed a sub-group analysis by Caucasian population using the same four models. CRP and TNF-α gene polymorphisms showed a positive significant association with CHD. This study provides evidence that rs2794521 of the CRP gene and rs1799724, rs1800630 and rs1799964 of the TNF-α gene polymorphisms may be risk factors to manifest CHD. The analysis of rs1800947 and rs1205 of the CRP gene yielded a protective effect in the pathogenesis of this disease. Only the analysis of the rs1130864 polymorphism showed a lack of association with CHD. To have conclusive outcomes it is necessary to integrate more studies to confirm our findings.

Gender differences in socio-demographic, clinical characteristics and psychiatric diagnosis in/of suicide attempters in a Mexican population.

OBJECTIVE: The aim of the present study was to analyse demographic and clinical characteristics, as well as psychiatric diagnoses to identify gender differences in patients with attempted suicide in a Mexican population. METHODS: Between September 2010 and September 2012, 140 suicide attempts were documented in the Department of Psychiatry at the General Hospital of Comalcalco (Hospital General de Comalcalco in Spanish) in Tabasco, Mexico. Diagnoses were established using the DSM-IV questionnaire in which Axis I and II were considered. The Suicide Intent Scale was also applied. RESULTS: In our sample, 63.6% were females and 36.4% males. With regard to socio-demographic characteristics, the predominant marital status in males was single, and in females married (χ2=5.93, df=2, p=0.05). In occupation the male group was mainly unemployed and housewife in females (χ2=55.51, df=4, p<0.001). Male subjects were more likely to consume alcohol (χ2=20.40, df=1, p≤0.001), cannabis (χ2=16.62, df=1, p≤0.001) or tobacco. The prevalence of psychiatric diagnosis was significantly different because, the male group was mainly diagnosed with substance-related disorders, whereas female participants showed a prevalence of stress-related disorders (χ2=34.17, gl=4, p=0.0001). CONCLUSION: Our results provide evidence that the characteristics of suicide attempt are different by gender in the Mexican population. Interventions are necessary for the development of prevention strategies that may lead to a reduction in suicidal behaviour. These preventive activities should consider the occupation for the female group and consumption of alcohol, cannabis or tobacco in the male group.