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Neuroscience and Biobehavioral Reviews Jun 2020MRI has enhanced our capacity to understand variations in brain structure and function conferred by the genome. We identified 60 studies that report associations between... (Review)
Review
MRI has enhanced our capacity to understand variations in brain structure and function conferred by the genome. We identified 60 studies that report associations between DNA methylation (DNAm) and human brain structure/function. Forty-three studies measured candidate loci DNAm; seventeen measured epigenome-wide DNAm. MRI features included region-of-interest and whole-brain structural, diffusion and functional imaging features. The studies report DNAm-MRI associations for: neurodevelopment and neurodevelopmental disorders; major depression and suicidality; alcohol use disorder; schizophrenia and psychosis; ageing, stroke, ataxia and neurodegeneration; post-traumatic stress disorder; and socio-emotional processing. Consistency between MRI features and differential DNAm is modest. Sources of bias: variable inclusion of comparator groups; different surrogate tissues used; variation in DNAm measurement methods; lack of control for genotype and cell-type composition; and variations in image processing. Knowledge of MRI features associated with differential DNAm may improve understanding of the role of DNAm in brain health and disease, but caution is required because conventions for linking DNAm and MRI data are not established, and clinical and methodological heterogeneity in existing literature is substantial.
Topics: Brain; DNA Methylation; Emotions; Epigenesis, Genetic; Epigenome; Genotype; Humans
PubMed: 32151655
DOI: 10.1016/j.neubiorev.2020.03.007 -
The Cochrane Database of Systematic... Apr 2023Neonates are an extremely vulnerable patient population, with 6% to 9% admitted to the neonatal intensive care unit (NICU) following birth. Neonates admitted to the NICU... (Review)
Review
BACKGROUND
Neonates are an extremely vulnerable patient population, with 6% to 9% admitted to the neonatal intensive care unit (NICU) following birth. Neonates admitted to the NICU will undergo multiple painful procedures per day throughout their stay. There is increasing evidence that frequent and repetitive exposure to painful stimuli is associated with poorer outcomes later in life. To date, a wide variety of pain control mechanisms have been developed and implemented to address procedural pain in neonates. This review focused on non-opioid analgesics, specifically non-steroidal anti-inflammatory drugs (NSAIDs) and N-methyl-D-aspartate (NMDA) receptor antagonists, which alleviate pain through inhibiting cellular pathways to achieve analgesia. The analgesics considered in this review show potential for pain relief in clinical practice; however, an evidence summation compiling the individual drugs they comprise and outlining the benefits and harms of their administration is lacking. We therefore sought to summarize the evidence on the level of pain experienced by neonates both during and following procedures; relevant drug-related adverse events, namely episodes of apnea, desaturation, bradycardia, and hypotension; and the effects of combinations of drugs. As the field of neonatal procedural pain management is constantly evolving, this review aimed to ascertain the scope of non-opioid analgesics for neonatal procedural pain to provide an overview of the options available to better inform evidence-based clinical practice. OBJECTIVES: To determine the effects of non-opioid analgesics in neonates (term or preterm) exposed to procedural pain compared to placebo or no drug, non-pharmacological intervention, other analgesics, or different routes of administration.
SEARCH METHODS
We searched the Cochrane Library (CENTRAL), PubMed, Embase, and two trial registries in June 2022. We screened the reference lists of included studies for studies not identified by the database searches.
SELECTION CRITERIA
We included all randomized controlled trials (RCTs), quasi-RCTs, and cluster-RCTs in neonates (term or preterm) undergoing painful procedures comparing NSAIDs and NMDA receptor antagonists to placebo or no drug, non-pharmacological intervention, other analgesics, or different routes of administration. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our main outcomes were pain assessed during the procedure and up to 10 minutes after the procedure with a validated scale; episodes of bradycardia; episodes of apnea; and hypotension requiring medical therapy.
MAIN RESULTS
We included two RCTs involving a total of 269 neonates conducted in Nigeria and India. NMDA receptor antagonists versus no treatment, placebo, oral sweet solution, or non-pharmacological intervention One RCT evaluated using oral ketamine (10 mg/kg body weight) versus sugar syrup (66.7% w/w at 1 mL/kg body weight) for neonatal circumcision. The evidence is very uncertain about the effect of ketamine on pain score during the procedure, assessed with the Neonatal Infant Pain Scale (NIPS), compared with placebo (mean difference (MD) -0.95, 95% confidence interval (CI) -1.32 to -0.58; 1 RCT; 145 participants; very low-certainty evidence). No other outcomes of interest were reported on. Head-to-head comparison of different analgesics One RCT evaluated using intravenous fentanyl versus intravenous ketamine during laser photocoagulation for retinopathy of prematurity. Neonates receiving ketamine followed an initial regimen (0.5 mg/kg bolus 1 minute before procedure) or a revised regimen (additional intermittent bolus doses of 0.5 mg/kg every 10 minutes up to a maximum of 2 mg/kg), while those receiving fentanyl followed either an initial regimen (2 μg/kg over 5 minutes, 15 minutes before the procedure, followed by 1 μg/kg/hour as a continuous infusion) or a revised regimen (titration of 0.5 μg/kg/hour every 15 minutes to a maximum of 3 μg/kg/hour). The evidence is very uncertain about the effect of ketamine compared with fentanyl on pain score assessed with the Premature Infant Pain Profile-Revised (PIPP-R) scores during the procedure (MD 0.98, 95% CI 0.75 to 1.20; 1 RCT; 124 participants; very low-certainty evidence); on episodes of apnea occurring during the procedure (risk ratio (RR) 0.31, 95% CI 0.08 to 1.18; risk difference (RD) -0.09, 95% CI -0.19 to 0.00; 1 study; 124 infants; very low-certainty evidence); and on hypotension requiring medical therapy occurring during the procedure (RR 5.53, 95% CI 0.27 to 112.30; RD 0.03, 95% CI -0.03 to 0.10; 1 study; 124 infants; very low-certainty evidence). The included study did not report pain score assessed up to 10 minutes after the procedure or episodes of bradycardia occurring during the procedure. We did not identify any studies comparing NSAIDs versus no treatment, placebo, oral sweet solution, or non-pharmacological intervention or different routes of administration of the same analgesics. We identified three studies awaiting classification. AUTHORS' CONCLUSIONS: The two small included studies comparing ketamine versus either placebo or fentanyl, with very low-certainty evidence, rendered us unable to draw meaningful conclusions. The evidence is very uncertain about the effect of ketamine on pain score during the procedure compared with placebo or fentanyl. We found no evidence on NSAIDs or studies comparing different routes of administration. Future research should prioritize large studies evaluating non-opioid analgesics in this population. As the studies included in this review suggest potential positive effects of ketamine administration, studies evaluating ketamine are of interest. Furthermore, as we identified no studies on NSAIDs, which are widely used in older infants, or comparing different routes of administration, such studies should be a priority going forward.
Topics: Aged; Humans; Infant, Newborn; Male; Analgesics; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Apnea; Body Weight; Bradycardia; Fentanyl; Ketamine; Pain; Pain, Procedural; Receptors, N-Methyl-D-Aspartate
PubMed: 37014033
DOI: 10.1002/14651858.CD015179.pub2 -
Clinical and Experimental Allergy :... Mar 2023The aim of this study was to systematically review the evidence across studies that assessed DNA methylome variations in association with food allergy (FA). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The aim of this study was to systematically review the evidence across studies that assessed DNA methylome variations in association with food allergy (FA).
DESIGN
A systematic review of the literature and meta-analysis were carried out within several databases. However, the risk of bias in the included articles was not evaluated.
DATA SOURCES
PubMed, Cochrane Database of Systematic Reviews, and Web of Science were used to search up to July 2022.
ELIGIBILITY CRITERIA
We included targeted and epigenome-wide association studies (EWASs) that assessed DNA methylome alterations in association with FA in adult or paediatric populations.
RESULTS
Among 366 publications, only 16 were retained, which were mainly focused on FA in children. Seven candidate gene-targeted studies found associations in Th1/Th2 imbalance (IL4, IL5, IL10, INFG, IL2 and IL12B genes), regulatory T cell function (FOXP3 gene), Toll-like receptors pathway (TLR2, CD14 genes) and digestive barrier integrity (FLG gene). Nine EWAS assessed the association with peanut allergy (n = 3), cow's milk allergy (n = 2) or various food allergens (n = 4). They highlighted 11 differentially methylated loci in at least two studies (RPS6KA2, CAMTA1, CTBP2, RYR2, TRAPPC9, DOCK1, GALNTL4, HDAC4, UMODL1, ZAK and TNS3 genes). Among them, CAMTA1 and RPS6KA2, and CTBP2 are involved in regulatory T cell function and Th2 cell differentiation, respectively. Gene-functional analysis revealed two enriched gene clusters involved in immune responses and protein phosphorylation. ChIP-X Enrichment Analysis 3 showed eight significant transcription factors (RXRA, ZBTB7A, ESR1, TCF3, MYOD1, CTCF, GATA3 and CBX2). Ingenuity Pathway Analysis identified canonical pathways involved, among other, in B cell development, pathogen-induced cytokine storm signalling pathway and dendritic cell maturation.
CONCLUSION
This review highlights the involvement of epigenomic alterations of loci in Th1/Th2 and regulatory T cell differentiation in both candidate gene studies and EWAS. These alterations provide a better insight into the mechanistic aspects in FA pathogenesis and may guide the development of epigenome-based biomarkers for FA.
Topics: Female; Animals; Cattle; Epigenome; Cell Line, Tumor; Transcription Factors; DNA-Binding Proteins; Food Hypersensitivity; Milk Hypersensitivity
PubMed: 36756739
DOI: 10.1111/cea.14277 -
European Journal of Neurology May 2023Non-(acute disseminated encephalomyelitis) (non-ADEM) encephalitis and/or fluid attenuated inversion recovery hyperintense lesions in... (Review)
Review
BACKGROUND AND PURPOSE
Non-(acute disseminated encephalomyelitis) (non-ADEM) encephalitis and/or fluid attenuated inversion recovery hyperintense lesions in anti-myelin-oligodendrocyte-glycoprotein-associated encephalitis with seizures (FLAMES) are rarely described in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies (Abs). The aim was (i) to describe the clinical features and disease course of children and adults with non-ADEM encephalitis and/or FLAMES associated with MOG Abs and (ii) to describe their association with other central nervous system autoantibodies.
METHODS
This was a systematic review following the PRISMA guidelines. Patients fulfilled criteria for non-ADEM encephalitis and/or FLAMES, and all were MOG Ab positive.
RESULTS
In total, 83 (79%) patients with non-ADEM encephalitis (48 also had FLAMES) and 22 (21%) with isolated FLAMES were included. At the first episode, children (n = 45) had more infections (11/45, 24.4%; p = 0.017) and more of the phenotype consisting of non-ADEM encephalitis (42/45, 93.3%; p = 0.014) than adults (n = 38). Children had more episodes consistent with working memory deficits (25/54, 46.3%; p = 0.014) but fewer psychiatric symptoms (16/54, 29.6%; p = 0.002). Twenty-eight (40.6%) of 69 patients had N-methyl-d-aspartate receptor (NMDAR) Abs in cerebrospinal fluid (CSF), being more frequent in adults (19/29, 65.5%; p < 0.001). Compared to negatives, positive CSF NMDAR Abs had more relapses (14/20, 70%; p = 0.050), required ventilatory support more frequently (8/34, 23.5%; p = 0.009) and had more psychiatric episodes (28/34, 82%; p < 0.001) or abnormal movements (14/34, 41.2%; p = 0.008). Apart from an older age in FLAMES, positive and negative CSF NMDAR Ab groups shared similar features.
CONCLUSION
Non-ADEM encephalitis patients with MOG Abs show specific clinical and radiological features, depending on the age at first episode. The presence of MOG Abs in non-ADEM encephalitis patients should not rule out to test other autoantibodies, especially concomitant NMDAR Abs in patients with suggestive symptoms such as behavioural or movement alterations.
Topics: Humans; Myelin-Oligodendrocyte Glycoprotein; Encephalitis; Encephalomyelitis, Acute Disseminated; Disease Progression; Autoantibodies
PubMed: 36704861
DOI: 10.1111/ene.15684 -
International Journal of Molecular... Aug 2023The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical...
The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical development are addressed in this review. A systematic literature search was conducted in three electronic databases (Medline, Web of Science, Scopus) and in the ClinicalTrials.gov register from 1 January 2016 to 1 June 2023 to identify Phase II, III and IV clinical trials evaluating drugs for the treatment of PHN. A total of 18 clinical trials were selected evaluating 15 molecules with pharmacological actions on nine different molecular targets: Angiotensin Type 2 Receptor (AT2R) antagonism (olodanrigan), Voltage-Gated Calcium Channel (VGCC) α2δ subunit inhibition (crisugabalin, mirogabalin and pregabalin), Voltage-Gated Sodium Channel (VGSC) blockade (funapide and lidocaine), Cyclooxygenase-1 (COX-1) inhibition (TRK-700), Adaptor-Associated Kinase 1 (AAK1) inhibition (LX9211), Lanthionine Synthetase C-Like Protein (LANCL) activation (LAT8881), N-Methyl-D-Aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone and hydromorphone) and Nerve Growth Factor (NGF) inhibition (fulranumab). In brief, there are several drugs in advanced clinical development for treating PHN with some of them reporting promising results. AT2R antagonism, AAK1 inhibition, LANCL activation and NGF inhibition are considered first-in-class analgesics. Hopefully, these trials will result in a better clinical management of PHN.
Topics: Humans; Drugs, Investigational; Nerve Growth Factor; Neuralgia, Postherpetic; Pregabalin; Randomized Controlled Trials as Topic
PubMed: 37629168
DOI: 10.3390/ijms241612987 -
The Cochrane Database of Systematic... Sep 2023Lumbar puncture (LP) is a common invasive procedure, most frequently performed to diagnose infection. Physicians perform LP in newborn infants with the help of an... (Review)
Review
BACKGROUND
Lumbar puncture (LP) is a common invasive procedure, most frequently performed to diagnose infection. Physicians perform LP in newborn infants with the help of an assistant using a strict aseptic technique; it is important to monitor the infant during all the steps of the procedure. Without adequate analgesia, LP can cause considerable pain and discomfort. As newborns have increased sensitivity to pain, it is crucial to adequately manage the procedural pain of LP in this population.
OBJECTIVES
To assess the benefits and harms, including pain, discomfort, and success rate, of any pharmacological intervention during lumbar puncture in newborn infants, compared to placebo, no intervention, non-pharmacological interventions, or other pharmacological interventions.
SEARCH METHODS
We searched CENTRAL, PubMed, Embase, and three trial registries in December 2022. We also screened the reference lists of included studies and related systematic reviews for studies not identified by the database searches.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) and quasi-RCTs comparing drugs used for pain management, sedation, or both, during LP. We considered the following drugs suitable for inclusion. • Topical anesthetics (e.g. eutectic mixture of local anesthetics [EMLA], lidocaine) • Opioids (e.g. morphine, fentanyl) • Alpha-2 agonists (e.g. clonidine, dexmedetomidine) • N-Methyl-D-aspartate (NMDA) receptor antagonists (e.g. ketamine) • Other analgesics (e.g. paracetamol) • Sedatives (e.g. benzodiazepines such as midazolam) DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We used the fixed-effect model with risk ratio (RR) for dichotomous data and mean difference (MD) or standardized mean difference (SMD) for continuous data, with their 95% confidence intervals (CIs). Our main outcomes were successful LP on first attempt, total number of LP attempts, episodes of bradycardia, pain assessed with validated scales, episodes of desaturation, number of episodes of apnea, and number of infants with one or more episodes of apnea. We used the GRADE approach to evaluate the certainty of the evidence.
MAIN RESULTS
We included three studies (two RCTs and one quasi-RCT) that enrolled 206 newborns. One study included only term infants. All studies assessed topical treatment versus placebo or no intervention. The topical anesthetics were lidocaine 4%, lidocaine 1%, and EMLA. We identified no completed studies on opioids, non-steroidal anti-inflammatory drugs, alpha-2 agonists, NMDA receptor antagonists, other analgesics, sedatives, or head-to-head comparisons (drug A versus drug B). Based on very low-certainty evidence from one quasi-RCT of 100 LPs in 76 infants, we are unsure if topical anesthetics (lidocaine), compared to no anesthesia, has an effect on the following outcomes. • Successful LP on first attempt (first-attempts success in 48% of LPs in the lidocaine group and 42% of LPs in the control group) • Number of attempts per LP (mean 1.9 attempts, [standard error of the mean 0.2] in the lidocaine group, and mean 2.1 attempts [standard error of the mean 2.1] in the control group) • Episodes of bradycardia (0% of LPs in the lidocaine group and 4% of LPs in the control group) • Episodes of desaturation (0% of LPs in the lidocaine group and 8% of LPs in the control group) • Occurrence of apnea (RR 3.24, 95% CI 0.14 to 77.79; risk difference [RD] 0.02, 95% CI -0.03 to 0.08). Topical anesthetics compared to placebo may reduce pain assessed with the Neonatal Facial Coding System (NFCS) score (SMD -1.00 standard deviation (SD), 95% CI -1.47 to -0.53; I² = 98%; 2 RCTs, 112 infants; low-certainty evidence). No studies in this comparison reported total number of episodes of apnea. We identified three ongoing studies, which will assess the effects of EMLA, lidocaine, and fentanyl. Three studies are awaiting classification.
AUTHORS' CONCLUSIONS
The evidence is very uncertain about the effect of topical anesthetics (lidocaine) compared to no anesthesia on successful lumbar puncture on first attempt, the number of attempts per lumbar puncture, episodes of bradycardia, episodes of desaturation, and occurrence of apnea. Compared to placebo, topical anesthetics (lidocaine or EMLA) may reduce pain assessed with the NFCS score. One ongoing study will assess the effects of systemic treatment.
Topics: Humans; Infant, Newborn; Analgesics; Anesthetics, Local; Apnea; Bradycardia; Fentanyl; Hypnotics and Sedatives; Lidocaine; Lidocaine, Prilocaine Drug Combination; Pain; Spinal Puncture
PubMed: 37767875
DOI: 10.1002/14651858.CD015594.pub2 -
Neuroscience and Biobehavioral Reviews Sep 2022Memory and motor deficits are commonly identified in Parkinson's disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is transformed to MPP+ via monoamine... (Meta-Analysis)
Meta-Analysis Review
Memory and motor deficits are commonly identified in Parkinson's disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is transformed to MPP+ via monoamine oxidase B (MAOB), which causes oxidative stress and destroys dopaminergic (DA) neurons in substantia nigra pars compacta (SNc) and is widely used to create animal models of PD. However, to-date, a comprehensive analysis of the MPTP effects on various aspects of PD does not exist. Here, we provide a systematic review and meta-analysis on the MPTP effects on memory and motor functions by analyzing 51 studies on more than one thousand animals mainly including rats and mice. The results showed that in addition to motor functions such as coordination, balance and locomotor activity, MPTP significantly affects various mnemonic processes including spatial memory, working memory, recognition memory, and associative memory compared with the control group with some differences between systemic and intra-nigral injections on spatial memory, familiar object recognition, and anxiety-like behaviors. Nevertheless, our analysis failed to find systematic relationship between MPTP injection protocol parameters reported and the extent of the induced PD symptoms that can be a cause of concern for replicability of MPTP studies.
Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Cognition; Disease Models, Animal; Mice; Parkinson Disease; Pyrrolidines; Rats; Rodentia
PubMed: 35872230
DOI: 10.1016/j.neubiorev.2022.104792 -
Gene Feb 2023Developmental dysplasia of the hip (DDH) is a complex developmental deformity whose pathogenesis and susceptibility-related genes have yet to be elucidated. This... (Review)
Review
BACKGROUND
Developmental dysplasia of the hip (DDH) is a complex developmental deformity whose pathogenesis and susceptibility-related genes have yet to be elucidated. This systematic review summarizes the current literature on DDH-related gene mutations, animal model experiments, and epigenetic changes in DDH.
METHODS
We performed a comprehensive search of relevant documents in the Medline, Scopus, Cochrane, and ScienceDirect databases covering the period from October 1991 to October 2021. We analyzed basic information on the included studies and summarized the DDH-related mutation sites, animal model experiments, and epigenetic changes associated with DDH.
RESULTS
A total of 63 studies were included in the analysis, of which 54 dealt with the detection of gene mutations, 7 presented details of animal experiments, and 6 were epigenetic studies. No genetic mutations were clearly related to the pathogenesis of DDH, including the most frequently studied genes on chromosomes 1, 17, and 20. Most gene-related studies were performed in Han Chinese or North American populations, and the quality of these studies was medium or low. GDF5 was examined in the greatest number of studies, and mutation sites with odds ratios > 10 were located on chromosomes 3, 9, and 13. Six mutations were found in animal experiments (i.e., CX3CR1, GDF5, PAPPA2, TENM3, UFSP2, and WISP3). Epigenetics research on DDH has focused on GDF5 promoter methylation, three microRNAs (miRNAs), and long noncoding RNAs. In addition, there was also a genetic test for miRNA and mRNA sequencing.
CONCLUSIONS
DDH is a complex joint deformity with a considerable genetic component whose early diagnosis is significant for preventing disease. At present, no genes clearly involved in the pathogenesis of DDH have been identified. Research on mutations associated with this condition is progressing in the direction of in vivo experiments in animal models to identify DDH susceptibility genes and epigenetics analyses to provide novel insights into its pathogenesis. In the future, genetic profiling may improve matters.
Topics: Humans; Animals; Developmental Dysplasia of the Hip; Hip Dislocation, Congenital; Epigenesis, Genetic; Mutation; Asian People; Membrane Proteins; Nerve Tissue Proteins
PubMed: 36435507
DOI: 10.1016/j.gene.2022.147067 -
Cancer May 2022H3G34-mutant diffuse hemispheric glioma (DHG) is recognized as a new, distinct entity in the latest World Health Organization classification for central nervous system... (Review)
Review
BACKGROUND
H3G34-mutant diffuse hemispheric glioma (DHG) is recognized as a new, distinct entity in the latest World Health Organization classification for central nervous system tumors and is associated with a particularly aggressive course. The authors performed a systematic review and pooled analysis to investigate the frequency of genetic events in these tumors and to determine whether these events were associated with survival trends.
METHODS
Two electronic databases were accessed to search for relevant data. Included criteria were studies that had individual patient data on H3.3 G34-mutant gliomas. To analyze the impact of genetic events on overall survival, Kaplan-Meier analysis and Cox regression models were used, and corresponding hazard ratios and 95% confidence intervals were computed.
RESULTS
In total, 20 studies with 257 H3G34-mutant DHGs were included for integrated analyses. The H3 glycine-to-valine (H3G34V) mutation showed a significantly worse prognosis than the glycine-to-arginine (H3G34R) mutation (median overall survival, 9.9 vs 14.8 months; hazard ratio, 3.040; 95% confidence interval, 1.208-7.651; P = .018), and this result remained statistically significant in the multivariate Cox regression model. Among H3G34 DHGs, TP53 mutation was the most common genetic alteration (94.9%), followed by ATRX alterations (87.5%), MGMT methylation (79.5%), and PDGFRA alterations (33.2%). The presence of PDGFRA amplification or EGFR amplification conferred poor survival. After adjusting for age and sex, these alterations were still independent indicators for adverse outcomes.
CONCLUSIONS
The authors highlight the important role of molecular stratification of H3G34 DHGs, which may help refine our understanding of the natural history of this group of malignant tumors.
Topics: Brain Neoplasms; Genotype; Glioma; Glycine; Humans; Prognosis
PubMed: 35195909
DOI: 10.1002/cncr.34156 -
Schizophrenia Bulletin Jul 2017Kynurenic acid (KYNA) is an endogenous antagonist of N-methyl-D-aspartate and α7 nicotinic acetylcholine receptors that is derived from astrocytes as part of the... (Meta-Analysis)
Meta-Analysis Review
Kynurenic acid (KYNA) is an endogenous antagonist of N-methyl-D-aspartate and α7 nicotinic acetylcholine receptors that is derived from astrocytes as part of the kynurenine pathway of tryptophan degradation. Evidence suggests that abnormal KYNA levels are involved in the pathophysiology of schizophrenia. However, this has never been assessed through a meta-analysis. A literature search was conducted through Ovid using Embase, Medline, and PsycINFO databases (last search: December 2016) with the search terms: (kynuren* or KYNA) and (schizophreni* or psychosis). English language studies measuring KYNA levels using any method in patients with schizophrenia and healthy controls (HCs) were identified. Standardized mean differences (SMDs) were calculated to determine differences in KYNA levels between groups. Subgroup analyses were separately performed for nonoverlapping participant samples, KYNA measurement techniques, and KYNA sample source. The influences of patients' age, antipsychotic status (%medicated), and sex (%male) on study SMDs were assessed through a meta-regression. Thirteen studies were deemed eligible for inclusion in the meta-analysis. In the main analysis, KYNA levels were elevated in the patient group. Subgroup analyses demonstrated that KYNA levels were increased in nonoverlapping participant samples, and centrally (cerebrospinal fluid and brain tissue) but not peripherally. Patients' age, %medicated, and %male were each positively associated with study SMDs. Overall, KYNA levels are increased in patients with schizophrenia, specifically within the central nervous system. An improved understanding of KYNA in patients with schizophrenia may contribute to the development of novel diagnostic approaches and therapeutic strategies.
Topics: Adult; Female; Humans; Kynurenic Acid; Male; Schizophrenia
PubMed: 28187219
DOI: 10.1093/schbul/sbw221