Inflammation and Nitro-Oxidative Stress in Current Suicidal Attempts and Current Suicidal Ideation: a Systematic Review and Meta-Analysis

A meta-analysis showed a significant association between activated immune-inflammatory and nitro-oxidative (IO&NS) pathways and suicide attempts (SA). There are no data whether suicidal ideation (SI) is accompanied by activated IO&NS pathways and whether there are differences between SA and SI. The current study searched PubMed, Google Scholar, and Web of Science, for articles published from inception until May 10, 2021, and systematically reviewed and meta-analyzed the association between recent SA/SI (< 3 months) and IO&NS biomarkers. We included studies which compared psychiatric patients with and without SA and SI and controls (either healthy controls or patients without SA or SI) and used meta-analysis (random-effect model with restricted maximum-likelihood) to delineate effect sizes with 95% confidence intervals (CI). Our search included 59 studies comprising 4.034 SA/SI cases and 12.377 controls. Patients with SA/SI showed activated IO&NS pathways (SMD: 0.299; CI: 0.200; 0.397) when compared to controls. The immune profiles were more strongly associated with SA than with SI, particularly when compared to healthy controls, as evidenced by activated IO&NS pathways (SMD: 0.796; CI: 0.503; 1.089), an immune-inflammatory response (SMD: 1.409; CI: 0.637; 1.462), inflammation (SMD: 1.200; CI: 0.584; 1.816), and neurotoxicity (SMD: 0.904; CI: 0.431; 1.378). The effects sizes of the IO&NS, immune-inflammatory response and inflammatory profile were significantly greater in SA than in SI. In conclusion: increased neurotoxicity due to inflammation and nitro-oxidative stress and lowered neuroprotection may explain at least in part why psychiatric patients show increased SA and SI. The IO&NS pathways are more pronounced in recent SA than in SI.

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Inflammation and nitro-oxidative stress in current suicidal attempts and current suicidal ideation: a systematic review and meta-analysis

10.1101/2021.09.09.21263363 ◽

2021 ◽

Author(s):

Asara Vasupanrajit ◽

Ketsupar Jirakran ◽

Chavit Tunvirachaisakul ◽

Marco Solmi ◽

Michael Maes

Keyword(s):

Oxidative Stress ◽

Suicidal Ideation ◽

Web Of Science ◽

Suicide Attempts ◽

Psychiatric Patients ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Healthy Controls ◽

Effect Model

AbstractA meta-analysis showed a significant association between activated immune-inflammatory and nitro-oxidative (IO&NS) pathways and suicide attempts (SA). There is no data on whether suicidal ideation (SI) is accompanied by activated IO&NS pathways and whether there are differences between SA and SI. The current study searched PubMed, Google Scholar, and Web of Science, for articles published from inception until May 10, 2021, and systematically reviewed and meta-analyzed the association between recent SA/SI (< 3 months) and IO&NS biomarkers. We included studies which compared psychiatric patients with and without SA and SI and controls (either healthy controls or patients without SA or SI) and used meta-analysis (random-effect model with restricted maximum-likelihood) to delineate effect sizes with 95% confidence intervals (CI). Our search included 59 studies comprising 4.034 SA/SI cases and 12.377 controls. Patients with SA/SI showed activated IO&NS pathways (SMD: 0.299; CI: 0.200; 0.397) when compared to controls. The immune profiles were more strongly associated with SA than with SI, particularly when compared to healthy controls, as evidenced by activated IO&NS (SMD: 0.796; CI: 0.503; 1.089), immune (SMD: 1.409; CI: 0.637; 1.462), inflammatory (SMD: 1.200; CI: 0.584; 1.816), and neurotoxic (SMD: 0.904; CI: 0.431; 1.378) pathways. The effects sizes of the IO&NS, immune and inflammatory profiles were significantly greater in SA than in SI. In conclusion: increased neurotoxicity due to inflammation and nitro-oxidative stress and lowered neuroprotection explains at least in part why psychiatric patients show increased SA and SI. The IO&NS pathways are more pronounced in recent SA than in SI.

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Increased Neurotoxicity Due to Activated Immune-Inflammatory and Nitro-Oxidative Stress Pathways in Patients with Suicide Attempts: A Systematic Review and Meta-Analysis

10.20944/preprints202104.0479.v1 ◽

2021 ◽

Author(s):

Asara Vasupanrajit ◽

Ketsupar Jirakran ◽

Chavit Tunvirachaisakul ◽

Michael Maes

Keyword(s):

Oxidative Stress ◽

Immune Activation ◽

Suicide Attempts ◽

Psychiatric Patients ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Control Group ◽

Healthy Controls ◽

New Biomarkers

Background: Suicide attempts (SA) frequently occur in patients with mood disorders and schizophrenia, which are both accompanied by activated immune-inflammatory and nitro-oxidative (IO&NS) pathways. Methods: We searched PubMed, Google Scholar, and Web of Science, for articles published from inception until February 1, 2021. We included studies that compared blood biomarkers in psychiatric patients with (SA+) and without SA (SA-) and heathy controls and we combined different IO&NS biomarkers into immune, inflammatory, and neurotoxic profiles and used meta-analysis (random-effect model with restricted maximum-likelihood) to delineate effect sizes with 95% confidence interval (CI).Findings: Our search included 51 studies comprising 4.945 SA+ patients and 24.148 controls. We stratified the control group into healthy controls and SA- patients. SA+ patients showed significantly (p<0.001) increased immune activation (SMD: 1.044; CI: 0.599-1.489), inflammation (SMD: 1.109; CI: 0.505, 1.714), neurotoxicity (SMD: 0.879; CI: 0.465, 1.293), and lowered neuroprotection (SMD: 0.648; CI: 0.354, 0.941) as compared with healthy controls. When compared with SA- patients, those with SA+ showed significant (p<0.001) immune activation (SMD: 0.290; CI: 0.183, 0.397), inflammation (SMD: 0.311; CI: 0.191, 0.432), and neurotoxicity (SMD: 0.315; CI: 0.198, 0.432), and lowered neuroprotection (SMD: 0.341; CI: 0.167, 0.515). Patients with current, but not lifetime, SA showed significant (p<0.001) levels of inflammation and neurotoxicity as compared with controls. Conclusions: Patients with immune activation are at a higher risk of SA which may be explained by increased neurotoxicity due to inflammation and nitro-oxidative stress. This meta-analysis discovered new biomarkers of SA and therapeutic targets to treat individuals with SA.

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Increased neurotoxicity due to activated immune-inflammatory and nitro-oxidative stress pathways in patients with suicide attempts: a systematic review and meta-analysis.

10.1101/2021.04.16.21255605 ◽

2021 ◽

Author(s):

Asara Vasupanrajit ◽

Ketsupar Jirakran ◽

Chavit Tunvirachaisakul ◽

Michael Maes

Keyword(s):

Oxidative Stress ◽

Immune Activation ◽

Suicide Attempts ◽

Psychiatric Patients ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Control Group ◽

Healthy Controls ◽

New Biomarkers

Background: Suicide attempts (SA) frequently occur in patients with mood disorders and schizophrenia, which are both accompanied by activated immune-inflammatory and nitro-oxidative (IO&NS) pathways. Methods: We searched PubMed, Google Scholar, and Web of Science, for articles published from inception until February 1, 2021. We included studies that compared blood biomarkers in psychiatric patients with (SA+) and without SA (SA-) and heathy controls and we combined different IO&NS biomarkers into immune, inflammatory, and neurotoxic profiles and used meta-analysis (random-effect model with restricted maximum-likelihood) to delineate effect sizes with 95% confidence interval (CI). Findings: Our search included 51 studies comprising 4.945 SA+ patients and 24.148 controls. We stratified the control group into healthy controls and SA- patients. SA+ patients showed significantly (p<0.001) increased immune activation (SMD: 1.044; CI: 0.599-1.489), inflammation (SMD: 1.109; CI: 0.505, 1.714), neurotoxicity (SMD: 0.879; CI: 0.465, 1.293), and lowered neuroprotection (SMD: 0.648; CI: 0.354, 0.941) as compared with healthy controls. When compared with SA- patients, those with SA+ showed significant (p<0.001) immune activation (SMD: 0.290; CI: 0.183, 0.397), inflammation (SMD: 0.311; CI: 0.191, 0.432), and neurotoxicity (SMD: 0.315; CI: 0.198, 0.432), and lowered neuroprotection (SMD: 0.341; CI: 0.167, 0.515). Patients with current, but not lifetime, SA showed significant (p<0.001) levels of inflammation and neurotoxicity as compared with controls. Conclusions: Patients with immune activation are at a higher risk of SA which may be explained by increased neurotoxicity due to inflammation and nitro-oxidative stress. This meta-analysis discovered new biomarkers of SA and therapeutic targets to treat individuals with SA.

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Alteration of Postural Balance in Patients with Fibromyalgia Syndrome—A Systematic Review and Meta-Analysis

Diagnostics ◽

10.3390/diagnostics11010127 ◽

2021 ◽

Vol 11 (1) ◽

pp. 127

Author(s):

David Núñez-Fuentes ◽

Esteban Obrero-Gaitán ◽

Noelia Zagalaz-Anula ◽

Alfonso Javier Ibáñez-Vera ◽

Alexander Achalandabaso-Ochoa ◽

...

Keyword(s):

Systematic Review ◽

Postural Balance ◽

Fibromyalgia Syndrome ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Healthy Controls ◽

Functional Balance ◽

Sensory Organization ◽

Effect Model

Balance problems are one of the most frequent symptoms in patients with Fibromyalgia Syndrome (FMS). However, the extent and nature of this balance disorder are not known. The objective of this work was to determine the best evidence for the alteration of postural balance in patients with FMS and analyze differences with healthy controls. To meet this objective, a systematic review with meta-analysis was performed. A bibliographical search was carried out in PubMed Medline, Scopus, Web of Science, CINAHL and SciELO. Observational studies that assessed postural balance in patients with FMS compared to healthy subjects in baseline conditions, were selected. In a random-effect model, the pooled effect was calculated with the Standardized Mean Difference (SMD) and its 95% confidence interval (CI). Nineteen studies reporting data of 2347 participants (95% female) were included. FMS patients showed poor balance with a large effect on static (SMD = 1.578; 95% CI = 1.164, 1.992), dynamic (SMD = 0.946; 95% CI = 0.598, 1.294), functional balance (SMD = 1.138; 95% CI = 0.689, 1.588) and on balance confidence (SMD = 1.194; 95% CI = 0.914, 1.473). Analysis of the Sensory Organization Test showed large alteration of vestibular (SMD = 1.631; 95% CI = 0.467, 2.795) and visual scores (SMD = 1.317; 95% CI = 0.153, 2.481) compared to healthy controls. Patients with FMS showed worse scores for different measures of postural balance compared to healthy controls. Concretely, FMS patients appear to have poor vestibular and visual scores with a possible somatosensory dependence.

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Association between circulating leptin levels and multiple sclerosis: a systematic review and meta-analysis

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2017-135397 ◽

2018 ◽

Vol 94 (1111) ◽

pp. 278-283 ◽

Cited By ~ 3

Author(s):

Xue-Feng Xie ◽

Xiao-Hui Huang ◽

Ai-Zong Shen ◽

Jun Li ◽

Ye-Huan Sun

Keyword(s):

Multiple Sclerosis ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Control Group ◽

Sample Type ◽

Healthy Controls ◽

Eligibility Criteria ◽

Effect Model ◽

Healthy Control

AimLeptin, synthesised by adipocytes, has been identified as a hormone that can influence inflammatory activity. Several studies have investigated leptin levels in patients with multiple sclerosis (MS), but the results are not consistent. This study aims to derive a more precise evaluation on the relationship between circulating leptin levels and MS.DesignA comprehensive literature searched up to July 2017 was conducted to evaluate the association of circulating leptin levels and MS. The random-effect model was applied to calculate pooled standardised mean difference (SMD) and its 95% CI.Main outcome measuresCirculating leptin levels of patients with MS and healthy controls.ResultsOf 2155 studies identified, 33 met eligibility criteria and 9 studies with 645 patients with MS and 586 controls were finally included in the meta-analysis. Meta-analysis revealed that, compared with the healthy control group, the MS group had significantly higher plasma/serum leptin levels, with the SMD of 0.70% and 95% CI (0.24 to 1.15). Subgroup analyses suggested that the leptin levels of patients with MS were associated with region, age, study sample size, measurement type, gender and blood sample type.ConclusionOverall, our study suggests that patients with MS have a significantly higher leptin level than in healthy controls. Further mechanism studies and longitudinal large cohort studies are still needed to further reveal the role of leptin in the pathogenesis of MS.

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Effects of melatonin supplementation on oxidative stress: a systematic review and meta-analysis of randomized controlled trials

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2020-0030 ◽

2020 ◽

Vol 41 (4) ◽

Author(s):

Parivash Ghorbaninejad ◽

Fatemeh Sheikhhossein ◽

Farhang Djafari ◽

Aliyu Jibril Tijani ◽

Saba Mohammadpour ◽

...

Keyword(s):

Oxidative Stress ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Protein Carbonyl ◽

Considerable Effect ◽

Controlled Trials ◽

Randomized Controlled ◽

Total Antioxidant

AbstractObjectivesPrevious studies showed that melatonin supplementation may suppress oxidative stress, however, the results have not been consistent. So, we conducted this meta-analysis to assess the precise relationship between melatonin supplementation and oxidative stress.MethodsPubMed and Scopus were searched for randomized controlled trials that investigated the effect of melatonin supplementation on oxidative stress up to March 2020. Heterogeneity was assessed by Cochran’s Q test and I-square (I2) statistic. Data were pooled using the random effect model and standardized mean difference (SMD) was considered as the summary effect size. Also, standard methods were used for assessment of sensitivity analysis and publication bias.ResultsWe included 15 related articles and our findings indicated that melatonin supplementation significantly increased total antioxidant capacity (TAC) level (SMD: 1.03, 95% CI: 0.24, 1.81, p=0.011) and reduced protein carbonyl (PCO) (SMD: −1.78, 95% CI: −2.97, −0.58, p=0.004) and malondialdehyde (MDA) levels (SMD: −0.94, 95% CI: −1.48, −0.40, p=0.001). Additionally, there was considerable effect on TAC level by using ≥20 mg/d melatonin and in people under 35 years old. MDA level also decreased using dosage of below 20 mg/d and in people ≥35 years old.ConclusionsThe present study showed a promising effect of melatonin administration for reducing MDA, PCO, and increasing TAC levels. However, further studies especially with more attention to PCO level assessment are needed to confirm the findings of the present study in larger samples on different populations.

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DHEA and polycystic ovarian syndrome: Meta-analysis of case-control studies

PLoS ONE ◽

10.1371/journal.pone.0261552 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0261552

Author(s):

Jiby Jolly Benjamin ◽

MaheshKumar K. ◽

Teena Koshy ◽

Maruthy K. N. ◽

Padmavathi R.

Keyword(s):

Polycystic Ovarian Syndrome ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Case Control ◽

Healthy Controls ◽

Polycystic Ovaries ◽

Case Control Studies ◽

Mesh Terms ◽

Ovarian Syndrome

Background Polycystic ovarian syndrome is a heterogenous endocrine disorder characterized by irregular menstrual cycles, hirsuitism and polycystic ovaries. It is further complicated by metabolic syndrome, infertility and psychological stress. Although the etiopathogenesis is unclear, many studies have pointed out the role of stress in this syndrome. DHEA, being a stress marker is being used by scientists to compare the stress levels between polycystic ovarian cases and healthy controls. However, the results obtained from previous studies are equivocal. Objective To perform meta-analysis and find the association between stress and the syndrome. Data sources Relevant data till January 2021 were retrieved from PubMed, Scopus, Embase and Web of Science using MeSH terms. Study selection Case-control studies having PCOS subjects as cases and healthy women as controls were selected provided; their basal DHEA levels were mentioned in the published articles. Data extraction Two authors independently extracted the articles and qualified the final studies. Data synthesi Pooled meta-analysis was done using random effect model and showed level of DHEA statistically significant in PCOS compared to healthy controls (SMD = 1.15, 95% CI = 0.59–1.71).Heterogeneity was statistically significant as well (I2 = 95%). Conclusion Thismeta-analysis on DHEA and PCOS has helped in generating evidence regarding the involvement of stress in the pathogenesis of PCOS.

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Driving us mad: the association of Toxoplasma gondii with suicide attempts and traffic accidents – a systematic review and meta-analysis

Psychological Medicine ◽

10.1017/s0033291719000813 ◽

2019 ◽

Vol 49 (10) ◽

pp. 1608-1623 ◽

Cited By ~ 16

Author(s):

Arjen L. Sutterland ◽

Anne Kuin ◽

Bouke Kuiper ◽

Tom van Gool ◽

Marion Leboyer ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Traffic Accidents ◽

Suicide Attempts ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Population Attributable Fraction ◽

Sensitivity Analyses ◽

Statistical Adjustment ◽

Antibody Titres

AbstractUnnatural causes of death due to traffic accidents (TA) and suicide attempts (SA) constitute a major burden on global health, which remained stable in the last decade despite widespread efforts of prevention. Recently, latent infection with Toxoplasma gondii (T. gondii) has been suggested to be a biological risk factor for both TA and SA. Therefore, a systematic search concerning the relationship of T. gondii infection with TA and/or SA according to PRISMA guidelines in Medline, Pubmed and PsychInfo was conducted collecting papers up to 11 February 2019 (PROSPERO #CRD42018090206). The random-effect model was applied and sensitivity analyses were subsequently performed. Lastly, the population attributable fraction (PAF) was calculated. We found a significant association for antibodies against T. gondii with TA [odds ratio (OR) = 1.69; 95% confidence interval (CI) 1.20–2.38, p = 0.003] and SA (OR = 1.39; 95% CI 1.10–1.76, p = 0006). Indication of publication bias was found for TA, but statistical adjustment for this bias did not change the OR. Heterogeneity between studies on SA was partly explained by type of control population used (ORhealthy controls = 1.9, p < 0.001 v. ORpsychiatric controls = 1.06, p = 0.87) and whether subjects with schizophrenia only were analysed (ORschizophrenia = 0.87, p = 0.62 v. ORvarious = 1.8, p < 0.001). The association was significantly stronger with higher antibody titres in TA and in studies that did not focus on schizophrenia subjects concerning SA. PAF of a T. gondii infection was 17% for TA and 10% for SA. This indicates that preventing T. gondii infection may play a role in the prevention of TA or SA, although uncertainty remains whether infection and outcome are truly causally related.

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Association between Serum Prolactin Levels and Neurodegenerative Diseases: Systematic Review and Meta-Analysis

NeuroImmunoModulation ◽

10.1159/000519552 ◽

2021 ◽

pp. 1-12

Author(s):

Hai Duc Nguyen ◽

Ngoc Minh Hong Hoang ◽

Myeonghee Ko ◽

Dongjin Seo ◽

Shinhyun Kim ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Detection Methods ◽

Cochrane Library ◽

Serum Prolactin ◽

Healthy Controls ◽

Standard Mean Difference ◽

Significant Difference

Introduction: Prolactin (PRL) exerts inflammatory and anti-inflammatory properties and is also thought to play an important role in the pathogenesis of neurodegenerative diseases (NDs). However, serum PRL levels in patients with NDs were inconsistent in the research literature. Objective: We aimed to assess the serum PRL levels in patients with NDs. Methods: Electronic databases, including MEDLINE, Embase, Cochrane Library database, clinicaltrials.gov, Web of Science, and Google Scholar, and reference lists of articles were searched up to December 31, 2020. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effect or random-effect model analysis. Results: A total of 36 comparisons out of 29 studies (3 RCTs and 26 case controls) focusing on NDs (including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease [HD], multiple sclerosis [MS], and epilepsy) were reported. The meta-analysis showed that there was no statistically significant difference in serum PRL levels between patients with NDs and healthy controls (SMD = 0.40, 95% CI: −0.16 to 0.96, p = 0.16). Subgroup analysis showed that serum PRL levels in patients with HD and MS were higher than those of healthy controls. Furthermore, patients with NDs aged <45 years had higher serum PRL levels (SMD = 0.97, 95% CI: 0.16–1.78, p = 0.018) than healthy controls. High serum PRL levels were found in subgroups such as the microenzymatic method, Asia, and the Americas. Conclusions: Our meta-analysis showed serum PRL levels in patients with HD and MS were significantly higher than those in healthy controls. Serum PRL levels were associated with age, region, and detection method. Other larger sample studies using more uniform detection methods are necessary to confirm our results.

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Prospective biomarkers of major depressive disorder: a systematic review and meta-analysis

Molecular Psychiatry ◽

10.1038/s41380-019-0585-z ◽

2019 ◽

Vol 25 (2) ◽

pp. 321-338 ◽

Cited By ~ 17

Author(s):

Mitzy Kennis ◽

Lotte Gerritsen ◽

Marije van Dalen ◽

Alishia Williams ◽

Pim Cuijpers ◽

...

Keyword(s):

Oxidative Stress ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Major Depressive ◽

Brain Volumes ◽

Effect Model ◽

Meta Analyses

AbstractLeading biological hypotheses propose that biological changes may underlie major depressive disorder onset and relapse/recurrence. Here, we investigate if there is prospective evidence for biomarkers derived from leading theories. We focus on neuroimaging, gastrointestinal factors, immunology, neurotrophic factors, neurotransmitters, hormones, and oxidative stress. Searches were performed in Pubmed, Embase and PsychInfo for articles published up to 06/2019. References and citations of included articles were screened to identify additional articles. Inclusion criteria were having an MDD diagnosis as outcome, a biomarker as predictor, and prospective design search terms were formulated accordingly. PRISMA guidelines were applied. Meta-analyses were performed using a random effect model when three or more comparable studies were identified, using a random effect model. Our search resulted in 67,464 articles, of which 75 prospective articles were identified on: Neuroimaging (N = 24), Gastrointestinal factors (N = 1), Immunology (N = 8), Neurotrophic (N = 2), Neurotransmitters (N = 1), Hormones (N = 39), Oxidative stress (N = 1). Meta-analyses on brain volumes and immunology markers were not significant. Only cortisol (N = 19, OR = 1.294, p = 0.024) showed a predictive effect on onset/relapse/recurrence of MDD, but not on time until MDD onset/relapse/recurrence. However, this effect disappeared when studies including participants with a baseline clinical diagnosis were removed from the analyses. Other studies were too heterogeneous to compare. Thus, there is a lack of evidence for leading biological theories for onset and maintenance of depression. Only cortisol was identified as potential predictor for MDD, but results are influenced by the disease state. High-quality (prospective) studies on MDD are needed to disentangle the etiology and maintenance of MDD.

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