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Journal of Affective Disorders Jan 2016Serotonin transporter-linked polymorphic region (5-HTTLPR) variants have been extensively studied in psychiatric disorders. Although gender effects have been reported,... (Review)
Review
BACKGROUND
Serotonin transporter-linked polymorphic region (5-HTTLPR) variants have been extensively studied in psychiatric disorders. Although gender effects have been reported, they have not been comprehensively reviewed. The aim of our study was to summarize literature findings on 5-HTTLPR and gender differences in affective disorders.
METHODS
A systematic search of PubMed, ISI Web of Knowledge, and PsycINFO databases was performed for dates until January 2015. The included articles (n=78) analyzed the association between 5-HTTLPR and affective spectrum disorders, taking into account gender. The quality of each study was assessed through STROBE and CONSORT.
RESULTS
5-HTTLPR modulation of affective disorders varied by gender. The S allele (or SS genotype) seemed to be differently associated with an increased risk of depression, depressive symptoms, anxiety traits and symptoms, and symptoms of internalizing behavior among women and an increased risk of aggressiveness, conduct disorder and symptom counts of externalizing behavior among men. Moreover, the presence of stressful life events reinforced the association. Interestingly, these differences seemed to begin with adolescence and were not consistent among the elderly, suggesting a plausible role of hormonal fluctuations.
LIMITATIONS
The review is limited by the small number of included papers, due to the paucity of information in the literature regarding 5-HTTLPR and gender.
CONCLUSIONS
5-HTTLPR variants may exert a differential modulation on a number of features depending on gender. Further studies are needed to more deeply investigate the effect of 5-HTTLPR×gender on the modulation of affective disorders.
Topics: Adolescent; Adult; Aged; Depression; Female; Genotype; Humans; Male; Middle Aged; Mood Disorders; Serotonin Plasma Membrane Transport Proteins; Sex Characteristics; Young Adult
PubMed: 26519640
DOI: 10.1016/j.jad.2015.09.027 -
Journal of Psychopharmacology (Oxford,... Nov 2023Major depressive disorder (MDD) is a leading cause of global disability. Several lines of evidence implicate the dopamine system in its pathophysiology. However, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Major depressive disorder (MDD) is a leading cause of global disability. Several lines of evidence implicate the dopamine system in its pathophysiology. However, the magnitude and consistency of the findings are unknown. We address this by systematically reviewing in vivo imaging evidence for dopamine measures in MDD and meta-analysing these where there are sufficient studies.
METHODS
Studies investigating the dopaminergic system using positron emission tomography or single photon emission computed tomography in MDD and a control group were included. Demographic, clinical and imaging measures were extracted from each study, and meta-analyses and sensitivity analyses were conducted.
RESULTS
We identified 43 studies including 662 patients and 801 controls. Meta-analysis of 38 studies showed no difference in mean or mean variability of striatal D receptor availability ( = 0.06, = 0.620), or combined dopamine synthesis and release capacity ( = 0.19, = 0.309). Dopamine transporter (DAT) availability was lower in the MDD group in studies using DAT selective tracers ( = -0.56, = 0.006), but not when tracers with an affinity for serotonin transporters were included ( = -0.21, = 0.420). Subgroup analysis showed greater dopamine release ( = 0.49, = 0.030), but no difference in dopamine synthesis capacity ( = -0.21, = 0.434) in the MDD group. Striatal D receptor availability was lower in patients with MDD in two studies.
CONCLUSIONS
The meta-analysis indicates striatal DAT availability is lower, but D receptor availability is not altered in people with MDD compared to healthy controls. There may be greater dopamine release and lower striatal D receptors in MDD, although further studies are warranted. We discuss factors associated with these findings, discrepancies with preclinical literature and implications for future research.
Topics: Humans; Dopamine; Depressive Disorder, Major; Tomography, Emission-Computed, Single-Photon; Positron-Emission Tomography; Receptors, Dopamine D2; Dopamine Plasma Membrane Transport Proteins
PubMed: 37811803
DOI: 10.1177/02698811231200881 -
Pediatric Neurology Jul 2022Hereditary hyperekplexia (HPX) is a genetic neurodevelopmental disorder recently defined by the triad of (1) neonatal hypertonia, (2) excessive startle reflexes, and (3)... (Review)
Review
Hereditary hyperekplexia (HPX) is a genetic neurodevelopmental disorder recently defined by the triad of (1) neonatal hypertonia, (2) excessive startle reflexes, and (3) generalized stiffness following the startle. Defects in GLRA1 are the most common cause of HPX, inherited both in an autosomal dominant and autosomal recessive manner. GLRA1 mutations can also cause milder phenotypes in the startle syndromes spectrum, but the prevalence is uncertain and no clear genotype-phenotype correlation has emerged yet. Moreover, the prevalence of neurodevelopmental outcomes has not been clearly defined. Here we report a new family of patients with a typical HPX phenotype, linked to a novel GLRA1 mutation, inherited with a recessive pattern. We then perform a systematic review of the literature of GLRA1-related HPX, describing the main epidemiological features of 210 patients. We found that GLRA1-related phenotypes do not necessarily fulfill the current criteria for HPX, including also milder and later-onset phenotypes. Among clinical features of the disease, neurodevelopmental issues were reported in a third of the sample; interestingly, we found that these problems, particularly when severe, were more common in homozygous than in heterozygous patients. Additional clinical and preclinical studies are needed to define predictors of adverse neurodevelopmental outcomes and underlying mechanisms.
Topics: Humans; Muscle Rigidity; Phenotype; Receptors, Glycine; Reflex, Startle; Stiff-Person Syndrome
PubMed: 35636282
DOI: 10.1016/j.pediatrneurol.2022.05.002 -
Oncotarget Jun 2017Increased glycolysis is one of the hallmarks of cancer. The abnormal expression of glucose transporter 1 (GLUT1) was reported to be associated with resistance to current... (Meta-Analysis)
Meta-Analysis Review
Increased glycolysis is one of the hallmarks of cancer. The abnormal expression of glucose transporter 1 (GLUT1) was reported to be associated with resistance to current therapy and poor prognosis. Numerous studies have investigated the correlation between GLUT1 expression and prognosis in cancers, but the conclusions are still controversial. Here, we conducted a meta-analysis to explore the association between GLUT1 and survival in human cancers. PubMed, Springer, Medline, and Cochrane Library were searched carefully to identify eligible studies evaluating prognostic value of GLUT1 in cancers. Twenty-seven studies with 4079 patients were included in the present study. Our pooled results identified that increased expression of GLUT1 was associated with unfavorable overall survival (HR = 1.780, 95% CI = 1.574-.013, p < 0.001)) and poorer disease-free survival (HR = 1.95, 95% CI = 1.229-3.095, p = 0.003). Furthermore, overexpression of GLUT1 linked with poor differentiated tumors (RR = 1.380, 95% CI = 1.086-1.755, p = 0.009; I2 = 72.0%, p < 0.001), positive lymph node metastasis (RR = 1.395, 95% CI = 1.082-1.799, p = 0.010; I2 = 70.8%, p = 0.002) and larger tumor size (RR = 1.405, 95% CI = 1.231-1.603, p < 0.001; I2 = 37.3%, p = 0.093). This systematic review and meta-analysis indicated that the GLUT1 may serve as an ideal prognostic biomarker in various cancers.
Topics: Biomarkers, Tumor; Glucose Transporter Type 1; Humans; Neoplasm Grading; Neoplasm Staging; Neoplasms; Prognosis; Proportional Hazards Models; Publication Bias
PubMed: 28498810
DOI: 10.18632/oncotarget.17445 -
BMJ Clinical Evidence Dec 2007Mortality from paracetamol overdose is now about 0.4%, although severe liver damage occurs without treatment in at least half of people with blood paracetamol levels... (Review)
Review
INTRODUCTION
Mortality from paracetamol overdose is now about 0.4%, although severe liver damage occurs without treatment in at least half of people with blood paracetamol levels above the UK standard treatment line. In adults, ingestion of less than 125 mg/kg is unlikely to lead to hepatotoxicity; even higher doses may be tolerated by children without causing liver damage.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute paracetamol poisoning? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2006 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 24 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: activated charcoal (single or multiple dose), gastric lavage, ipecacuanha, liver transplant, methionine, N-acetylcysteine.
Topics: Acetaminophen; Administration, Oral; Analgesics, Non-Narcotic; Benzodiazepines; Charcoal; Drug Overdose; Humans; Receptors, N-Methyl-D-Aspartate
PubMed: 19450343
DOI: No ID Found -
Journal of Integrative Neuroscience Feb 2024Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist with Connective Tissue Diseases (CTD) in patients with a high susceptibility to autoimmune conditions. However, the relationship between NMOSD and rheumatologic diseases deserves further investigations to clarify all clinical aspects of this coexistence. We designed a systematic review and a proportional meta-analysis to estimate the association between CTD and MNOSD, with the aim of helping to plan the best strategy to achieve the most significant public health benefit for these conditions.
METHODS
We conducted a systematic review of the literature published until February 2023, searching in four databases: PubMed, Web of Science, EmBase, and OVID. Then, we conducted a random-effects proportional meta-analysis and assessed the risk of bias of the included studies using the Joanna Briggs Institute checklist.
RESULTS
The literature search yielded an overall result of 3176 publications (272 from PubMed, 880 from Web of Science, 634 from EmBase and 1390 from OVID). Of these, 29 were included in this systematic review. Analyzing studies that recruited unselected patients with Systemic Lupus Erythematosus (SLE) and Sjogren Syndrome (SjS), the pooled percentages of NMOSD overlapping were 0.6% (95% Confidence Interval [95% CI]: 0.1%-1.4%,) and 6.5% (95% CI: 4.7-8.6), respectively. Studies enrolling rheumatologic patients with nervous system symptoms involvement reported higher percentage of NMOSD (i.e., among SjS patients, a pooled percentage of 26.5%, 95% CI: 5.5-54.6%, was found). Similarly, recruiting patients with NMOSD, we found pooled percentages of SjS or SLE respectively of 7.0% and 3.5%.
CONCLUSIONS
Our research found that the coexistence of these two disorders was more frequent in female rheumatologic patients with a SjS diagnosis with neurological manifestations and in neurologic patients for whom a SjS diagnosis was suspected. Similarly, NMOSD are less frequently found in SLE and very rarely incident in Mixed Connective Tissue Disease (MCTD) patients. These considerations should be taken into account in clinical experience of rheumatologists and neurologists, since early diagnosis of both conditions may influence the timing of immunosuppressive therapy and the prevention of systemic disabilities.
Topics: Humans; Female; Neuromyelitis Optica; Aquaporin 4; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid
PubMed: 38419451
DOI: 10.31083/j.jin2302035 -
PloS One 20145-Hydroxytryptamine receptor (5-HTR) and 5-hydroxytryptamine transporter (5-HTT) gene polymorphisms have been reported to be associated with susceptibility to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
5-Hydroxytryptamine receptor (5-HTR) and 5-hydroxytryptamine transporter (5-HTT) gene polymorphisms have been reported to be associated with susceptibility to obstructive sleep apnea syndrome (OSAS). The associations, derived from sporadic, inconsistent, small-sample-size studies, need to be evaluated further in a meta-analysis.
METHODS
Relevant studies were identified by searching PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu. Eligible data were extracted from each included study. Odds ratios (ORs) were calculated using a fixed-effects or a random-effects model. The ORs and 95% confidence interval (CI) were used to assess the strength of the association between serotonergic gene polymorphisms and OSAS in the dominant and recessive models, as well as alleles. The Q statistic was used to evaluate homogeneity and Begg's test was used to assess publication bias.
RESULTS
Eight studies were finally included in the meta-analysis of the association between 5-HTR2A gene variants (including 102T/C and 1438G/A), 5-HTT gene polymorphisms (including 5-HTT gene-linked promoter region (5-HTTLRP), and serotonin transporter intron 2 variable number tandem repeat (STin2VNTR) and OSAS risk. The G allele of 5-HTR2A 1438G/A, long 5-HTTLPR, and 10-tandem-repeats STin2VNTR were shown to increase OSAS susceptibility, with ORs of 2.33 (A vs. G, 95% CI 1.48-3.66), 1.24 (L vs. S, 95% CI: 1.04-1.49), and 2.87 (10 vs. 12, 95% CI: 1.38-5.97), respectively. These significant differences were determined in both dominant and recessive models. Of the 5-HTR2A 1438G/A gene polymorphism, the AA genotype increased the OSAS risk, with an OR of 4.21 (95% CI: 2.83-6.25) in a recessive model in male OSAS patients, but no significant association was found in females.
CONCLUSIONS
Our meta-analysis demonstrated that polymorphisms in the 5-HTR2A 1438G/A and 5-HTT genes contributed to susceptibility to OSAS. The A allele of the 1438G/A gene polymorphism is predominantly distributed in males and increased the OSAS risk significantly.
Topics: Female; Genetic Association Studies; Humans; Male; Receptor, Serotonin, 5-HT2A; Serotonin Plasma Membrane Transport Proteins; Sex Factors; Sleep Apnea, Obstructive
PubMed: 24475124
DOI: 10.1371/journal.pone.0086460 -
Neurogenetics May 2021Dravet syndrome (DS) is a rare and severe epileptic syndrome of childhood with prevalence between 1/22,000 and 1/49,900 of live births. Approximately 80% of patients... (Comparative Study)
Comparative Study
Dravet syndrome (DS) is a rare and severe epileptic syndrome of childhood with prevalence between 1/22,000 and 1/49,900 of live births. Approximately 80% of patients with this syndrome present SCN1A pathogenic variants, which encodes an alpha subunit of a neural voltage-dependent sodium channel. There is a correlation between PCDH19 pathogenic variants, encodes the protocadherin 19, and a similar disease to DS known as DS-like phenotype. The present review aims to clarify the differences between DS and DS-like phenotype according to the SCN1A and PCDH19 variants. A systematic review was conducted in PubMed and Virtual Health Library (VHL) databases, using "Dravet Syndrome" and "Severe Myoclonic Epilepsy in Infancy (SMEI)" search words, selecting cohort of studies published in journal with impact factor of two or greater. The systematic review was according to the Preferred Reporting Items for Systematic Review and Meta-Analysis recommendations. Nineteen studies were included in the present review, and a significant proportion of patients with DS-carrying SCN1A was greater than patients with DS-like phenotype-harboring PCDH19 variants (76.6% versus 23.4%). When clinical and genetic data were correlated, autism was predominantly observed in patients with DS-like-carrying PCDH19 variants compared to SCN1A variant carriers (62.5% versus 37.5%, respectively, P-value = 0.044, P-value corrected = 0.198). In addition, it was noticed a significant predisposition to hyperthermia during epilepsy crisis in individuals carrying PCDH19 variants (P-value = 0.003; P-value corrected = 0.027). The present review is the first to point out differences between the DS and DS-like phenotype according to the SCN1A and PCDH19 variants.
Topics: Autistic Disorder; Epilepsies, Myoclonic; Genetic Heterogeneity; Humans; Hyperthermia; Mutation; NAV1.1 Voltage-Gated Sodium Channel; Observational Studies as Topic; Phenotype; Protocadherins; Seizures, Febrile; Syndrome
PubMed: 33937968
DOI: 10.1007/s10048-021-00644-7 -
Rheumatology International Feb 2012The aim of this study was to explore whether the candidate gene polymorphisms contribute to fibromyalgia susceptibility. The authors conducted a meta-analysis on... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to explore whether the candidate gene polymorphisms contribute to fibromyalgia susceptibility. The authors conducted a meta-analysis on associations between serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) S/L allele, catechol-O-methltransferase (COMT) val158Met, and serotonin 2A (5-HT2A) receptor 102T/C polymorphisms and fibromyalgia susceptibility as determined using the following: (1) allele contrast, (2) recessive, (3) dominant models, and (4) contrast of homozygotes. We also performed a systematic review with available data of the candidate genes. A total of 21 separate comparisons were considered in this systematic review and meta-analysis. Seventeen candidate genes and over 35 different polymorphisms were identified in studies on fibromyalgia susceptibility. Meta-analysis of the 5-HTTLPR S/L allele and COMT val158Met failed to reveal any association with fibromyalgia. However, meta-analysis of the C allele, CC + CT genotype, and CC versus TT genotype of the 5-HT2A receptor 102T/C polymorphism showed significant association with fibromyalgia. The overall OR of the association between the C allele and fibromyalgia was 1.333 (95% CI = 1.053-1.688, P = 0.017). The ORs for the CC + CT genotype, and CC versus TT genotype showed the same pattern as that observed for the C allele (OR = 1.541, 95% CI = 1.032-2.303, P = 0.035; OR = 1.838, 95% CI = 1.151-2.936, P = 0.011). This meta-analysis demonstrates that the 5-HT2A receptor 102T/C polymorphism confers susceptibility to fibromyalgia. In contrast, no association was found between the 5-HTTLPR S/L allele, COMT val158Met, and susceptibility to fibromyalgia.
Topics: Alleles; Catechol O-Methyltransferase; Fibromyalgia; Genes, Dominant; Genes, Recessive; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Receptor, Serotonin, 5-HT2A; Receptors, Neurotransmitter; Serotonin Plasma Membrane Transport Proteins
PubMed: 21120487
DOI: 10.1007/s00296-010-1678-9 -
European Journal of Pain (London,... Aug 2019N-methyl-D-aspartate (NMDA) receptors are involved in pain signalling and neuroplasticity. Memantine has been shown to have analgesic properties in pre-clinical and... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
N-methyl-D-aspartate (NMDA) receptors are involved in pain signalling and neuroplasticity. Memantine has been shown to have analgesic properties in pre-clinical and small clinical studies. We conducted a systematic review and meta-analysis to assess the efficacy of memantine to prevent or reduce chronic pain.
DATABASES AND DATA TREATMENT
MEDLINE, EMBASE and CENTRAL databases were searched for comparative trials using memantine, either against placebo or active medications, for chronic pain in adults. Pain relief was considered our primary outcome. Meta-analyses were conducted if outcomes were reported in two or more studies. Outcomes were reported as mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI). Quality was assessed using the GRADE approach.
RESULTS
Among 454 citations, 15 studies were included with populations predominantly consisting of neuropathic conditions and fibromyalgia. Overall, we observed unclear reporting of randomization and allocation methods, apart from potential for publication bias. Among the 11 studies looking at chronic pain treatment, the difference in end pain score with memantine was not significant: MD = -0.58 units (95% CI -1.31, 0.14); I = 82% (low quality). In two surgical studies using memantine for pain prevention, memantine decreased pain intensity: MD = -1.02 units (95% CI -1.38, -0.66); I = 0%. Dizziness was significantly more common with memantine: RR = 4.90 (95% CI 1.26, 18.99); I = 52% (moderate quality).
CONCLUSION
The current evidence regarding the use of memantine for chronic pain is limited and uncertain. Despite its potential, pain relief achieved in clinical studies is small and is associated with an increase in dizziness.
SIGNIFICANCE
Despite a sound rationale, the benefit of using memantine for chronic pain is unclear. Our systematic review and meta-analysis show that memantine may have the potential to decrease pain. However, it can also increase common adverse effects. Considering the small number of studies with potential for bias and inconclusive evidence, there was low to very low certainty. Hence, no clear recommendations can be made about its routine clinical use until larger and more definitive studies are conducted.
Topics: Adult; Analgesics; Chronic Pain; Fibromyalgia; Humans; Memantine; Receptors, N-Methyl-D-Aspartate
PubMed: 30848504
DOI: 10.1002/ejp.1393