RESUMO
Contemporary research on the genomics of Attention Deficit Hyperactivity Disorder (ADHD) often underrepresents admixed populations of diverse genomic ancestries, such as Latin Americans. This study explores the relationship between admixture and genetic associations for ADHD in Colombian and Mexican cohorts. Some 546 participants in two groups, ADHD and Control, were genotyped with Infinium PsychArray®. Global ancestry levels were estimated using overall admixture proportions and principal component analysis, while local ancestry was determined using a method to estimate ancestral components along the genome. Genome-wide association analysis (GWAS) was conducted to identify significant associations. Differences between Colombia and Mexico were evaluated using appropriate statistical tests. 354 Single-nucleotide polymorphisms (SNPs) and Single-nucleotide variants (SNVs) related to some genes and intergenic regions exhibited suggestive significance (p-value < 5*10e-5) in the GWAS. None of the variants revealed genome-wide significance (p-value < 5*10e-8). The study identified a significant relationship between risk SNPs and the European component of admixture, notably observed in the LOC105379109 gene. Despite differences in risk association loci, such as FOXP2, our findings suggest a possible homogeneity in genetic variation's impact on ADHD between Colombian and Mexican populations. Current reference datasets for ADHD predominantly consist of samples with high European ancestry, underscoring the need for further research to enhance the representation of reference populations and improve the identification of ADHD risk traits in Latin Americans.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Predisposição Genética para Doença , Adolescente , Criança , Feminino , Humanos , Masculino , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estudos de Coortes , Colômbia/epidemiologia , Estudo de Associação Genômica Ampla , Genótipo , México/epidemiologia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Several association studies have indicated that the HTR1A gene is associated with suicidal behavior (SB). Thus, a systematic assessment of the association of HTR1A was performed based on a literature review and pooled analysis. Four electronic databases were comprehensively searched to find and pinpoint all case-control articles related to this study. When analyzing the genetic association with SB, data were divided into: (A) SB cases vs. healthy controls and (B) SB cases vs. psychiatric controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were assessed as measures of association. Heterogeneity among included studies was analyzed using sensitivity test and Q statistics. Publication bias was also explored by Egger and rank correlation test. Thirteen case-control studies were selected in this meta-analysis, involving 2817 SB patients, 2563 healthy controls and 545 psychiatric controls. In the overall comparison between SB cases and healthy controls, result showed that the rs6295 polymorphisms of HTR1A gene was associated with SB, but only when using the recessive model (OR = 2.21, 95% CI = 1.80-2.71, P < 0.001). In the smaller sample size comparison between SB and psychiatric controls, no significant association was detected with rs6295 in any of the five genetics models tested. The present meta-analysis suggests that rs6295 polymorphism of HTR1A gene could increase the risk for SB. Well-designed studies with more patients will be required to validate these results.
Assuntos
Polimorfismo de Nucleotídeo Único , Ideação Suicida , Humanos , Estudos de Casos e Controles , Razão de Chances , Predisposição Genética para Doença , Receptor 5-HT1A de Serotonina/genéticaRESUMO
BACKGROUND: In the TYMS gene promoter, there is a repeat polymorphism (TSER) that affects the expression level of the thymidylate synthetase (TS) enzyme involved in the response to some anticancer drugs. The G>C transversion located in the TSER*3R allele decreases the expression level of the TS enzyme avoiding the upstream stimulatory factor (USF-1) binding site. Despite the biomedical impact of the SNP G>C, only TSER has been reported in most worldwide populations. Thus, we studied both TSER and SNP G>C variants in the Mexican population. SUBJECTS AND METHODS: A population sample (n = 156) was genotyped for the TSER and G>C variants by PCR and PCR-RFLPs, respectively, followed by PAGE and silver staining. RESULTS: For TSER, the most frequent allele was 2 R (52.56%), as well as the genotype 2 R/3R (42.3%). Comparison with Latin American, European, and American (USA) populations suggest a heterogeneous worldwide distribution (FST-value = 0.01564; p-value = 0.0000). When the G>C variant was included (2RG, 3RG, and 3RC), a high frequency of low expression genotypes was observed: 2RG/2RG, 2RG/3RC, and 3RC/3RC (84.6%). CONCLUSION: The high frequency of genotypes associated with low TS enzyme expression justifies obtaining the TYMS gene variant profile in Mexican patient's candidates to pharmaceutical treatments like 5'-Fluoracil, methotrexate, and pemetrex.
Assuntos
Fluoruracila , Polimorfismo Genético , Timidilato Sintase , Humanos , Alelos , Genótipo , Polimorfismo de Fragmento de Restrição , Timidilato Sintase/genética , Timidilato Sintase/metabolismo , MéxicoRESUMO
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.
Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Risperidona/efeitos adversos , Esquizofrenia/tratamento farmacológico , Interleucina-6 , Antipsicóticos/efeitos adversosRESUMO
Background and Objectives: Poor sleep quality has been frequently observed in individuals with rheumatoid arthritis. In the present study, we analyzed the presence of poor sleep quality in a sample of Mexican individuals with rheumatoid arthritis; then, we compared sociodemographic and clinical characteristics among patients to determine risk factors for poor sleep quality. Materials and Methods: In this cross-sectional study, we included 102 individuals with rheumatoid arthritis from a hospital in Mexico. We evaluated disease activity (DAS28), quality of sleep using the Pittsburgh Sleep Quality Index, and the presence of depression and anxiety with the Hospital Anxiety and Depression Scale. We performed a Chi-square test and a t-test. Then, we performed a logistic regressions model of the associated features in a univariable analysis. Results: Poor sleep quality was observed in 41.75% of the individuals with rheumatoid arthritis. Being married was a proactive factor (OR 0.04, 95% CI 0.1-0.9, p = 0.04), whereas having one's hips affected or presenting with anxiety and depression was associated with poor sleep quality (OR 4.6, 95% CI 1.2-17.69, p = 0.02). After a multivariate analysis, having anxiety (OR 5.0, 95% CI 1.4-17.7, p < 0.01) and depression (OR 9.2, 95% CI 1.0-8.1, p < 0.01) remained associated with a higher risk of having poor sleep quality. Other clinical characteristics among patients were not significantly different. Conclusions: Our results showed that individuals with rheumatoid arthritis who also presented with depression or anxiety had a higher risk of suffering from poor sleep quality. However, more studies with larger samples are necessary to replicate these results in the Mexican population.
Assuntos
Artrite Reumatoide , Qualidade do Sono , Humanos , Estudos Transversais , Prevalência , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , SonoRESUMO
Two new umbravirus-like associated RNAs (ulaRNAs) were found, respectively, in maize and Johnsongrass samples from Ecuador. The complete sequences consist of 3,053 and 3,025 nucleotides, respectively, and contain four open reading frames (ORFs). Their genome sequences were 58% identical to each other and 28 to 60% identical to the most closely related viruses. Phylogenetic analysis using full genome sequences and amino acid sequence of the RNA-dependent-RNA polymerase (RdRp) placed both sequences in a clade sharing the most recent common ancestor with ulaRNAs from sugarcane and maize, suggesting that they belong to a monophyletic grass-infecting lineage. Their terminal regions exhibit features common to umbraviruses and ulaRNAs.
Assuntos
Sorghum , Tombusviridae , Equador , Genoma Viral , Fases de Leitura Aberta , Filogenia , RNA , RNA Viral/genética , Tombusviridae/genética , Zea maysRESUMO
BACKGROUND: MATE2-K is an efflux transporter protein of organic cation expressed mainly in the kidney and encoded by the SLC47A2 gene. Different variants of this gene have shown an impact on the pharmacokinetics of various drugs, including metformin, which represents one of the most widely used drugs in treating type 2 diabetes. The SLC47A2 gene variants have been scarcely studied in Mexican populations, especially in Native American groups. For this reason, we analyzed the distribution of the variants rs12943590, rs35263947, and rs9900497 within the SLC47A2 gene in 173 Native Americans (Tarahumara, Huichol, Maya, Puerépecha) and 182 Mestizos (admixed) individuals from Mexico. METHODS AND RESULTS: Genotypes were determined through TaqMan probes (qPCR). The Hardy-Weinberg agreement was confirmed for all three SLC47A2 gene variants in all the Mexican populations analyzed. When worldwide populations were included for comparison purposes, for alleles and genotypes a relative interpopulation homogeneity was observed for rs35263947 (T allele; range 23.3-51.1%) and rs9900497 (T allele; range 18.6-40.9%). Conversely, heterogeneity was evident for rs12943590 (A allele, range 22.1-59.1%), where the most differentiated population was the Huichol, with high frequencies of the risk genotype associated with decreased response to metformin treatment (A/A = 40.9%). CONCLUSIONS: Although the SLC47A2 gene variants allow predicting favorable response to the metformin treatment in Mexican populations, the probable high frequency of ineffectiveness should be discarded in Huichols.
Assuntos
Indígena Americano ou Nativo do Alasca/genética , Genética Populacional/métodos , Indígenas Norte-Americanos/genética , Proteínas de Transporte de Cátions Orgânicos/genética , Polimorfismo de Nucleotídeo Único , Alelos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Frequência do Gene , Haplótipos , Voluntários Saudáveis , Humanos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , México/etnologia , Plantas Medicinais , Resultado do TratamentoRESUMO
Schizophrenia is a debilitating mental illness. Levels of oxytocin have been proposed as a biomarker of schizophrenia; however, the observed levels of oxytocin in individuals with schizophrenia have been inconsistent across studies. We performed a meta-analysis to evaluate oxytocin levels in plasma, serum and cerebrospinal fluid to see if there are statistically different concentrations between individuals with schizophrenia and the comparison group. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Following the inclusion and exclusion criteria, 14 studies were included in the meta-analysis. The quality of the study was evaluated by the Newcastle-Ottawa Scale (NOS). A random-effects model was performed using the Comprehensive Meta-analysis software with the standardized mean difference (SMD) and 95% confidence intervals (CIs). Serum oxytocin levels in individuals with schizophrenia were significantly lower than that in comparison group (SMD = - 1.74, 95% CI = - 3.22 to - 0.26, p = 0.02) but cerebrospinal fluid oxytocin levels in individuals with schizophrenia were significantly higher than those in the comparison group (SMD = 0.55, 95% CI = 0.05 to 1.04, p = 0.03). Our results suggest that oxytocin levels in cerebrospinal fluid are increased in individuals with schizophrenia but decreased in serum. Therefore, the oxytocin system dysregulation may play a role in the pathophysiology of schizophrenia and it should be measured in more populations for a possible implementation as a biomarker of schizophrenia.
Assuntos
Ocitocina , Esquizofrenia , Biomarcadores , HumanosRESUMO
Objective: We conducted a meta-analysis of case-control studies to determine whether leptin levels in serum contribute to the pathogenesis of suicide behavior.Methods: PubMed, EBSCO and Science Direct databases were used to search for relevant articles published before January 2020. The systematic review included nine case-control studies that measured leptin levels. The standardized mean difference (d) and 95% confidence intervals were calculated in a fixed-effects model and a random-effects model when appropriate.Results: The results of our meta-analysis indicated that individuals with suicide behavior presented reduced levels of leptin (d: -1.80, 95% CI: -2.21 to -01.38 ng/ml, I2 = 0, p(Q) = 0.59). Sensitivity and publication bias analyses confirmed these results.Conclusions: The current meta-analysis suggests that leptin levels might be associated with an increased risk of suicide behavior. However, more studies including larger sample sizes are needed to reach conclusive result.
Assuntos
Leptina/sangue , Ideação Suicida , Suicídio/psicologia , Biomarcadores/sangue , Estudos de Casos e Controles , HumanosRESUMO
Patients with substance use disorders (SUD) are at high risk to die by suicide. So far, the neurobiology of the suicide-SUD association has not been elucidated. This study aimed to identify potential pharmacological targets among hub genes from brain gene co-expression networks of individuals with SUD in a suicidal and non-suicidal context. Post-mortem samples from the prefrontal cortex of 79 individuals were analyzed. Individuals were classified into the following groups: suicides with SUD (n = 28), suicides without SUD (n = 23), nonsuicides with SUD (n = 9), nonsuicides without SUD (n = 19). Gene expression profiles were evaluated with the Illumina HumanHT-12 v4 array. Co-expression networks were constructed in WGCNA using the differentially expressed genes found in the comparisons: (a) suicides with and without SUD and (b) nonsuicides with and without SUD. Hub genes were selected for drug-gene interaction testing in the DGIdb database. Among drugs interacting with hub genes in suicides we found MAOA inhibitors and dextromethorphan. In the nonsuicide individuals, we found interactions with eglumegad and antipsychotics (olanzapine, clozapine, loxapine). Modafinil was found to interact with genes in both suicides and nonsuicides. These drugs represent possible candidate treatments for patients with SUD with and without suicidal behavior and their study in each context is encouraged.
Assuntos
Antipsicóticos/farmacologia , Encéfalo/efeitos dos fármacos , Reposicionamento de Medicamentos/métodos , Redes Reguladoras de Genes/efeitos dos fármacos , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Prevenção do Suicídio , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/metabolismo , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Substâncias/genética , Transtornos Relacionados ao Uso de Substâncias/patologia , Transcriptoma , Adulto JovemRESUMO
Orexins-A (OrxA) and -B (OrxB) neuropeptides are synthesized by a group of neurons located in the lateral hypothalamus and adjacent perifornical area, which send their projections to the mesolimbic dopaminergic (DAergic) system including ventral tegmental area and nucleus accumbens (NAc), where orexin receptors are expressed. NAc plays a central role in reward-seeking behavior and drug abuse. NAc-neurons express dopamine-1 (D1R) and dopamine-2 (D2R) receptors. Orexins bind to their two cognate G-protein-coupled receptors, orexin-receptor type-1 (Orx1R) and type-2 (Orx2R). Orexin receptor signaling is involved in behaviors such as motivation and addiction. Orexin-containing neurons modulate DAergic activity that is key in synaptic plasticity induced by addictive drugs. However, the effect of OrxA on expression and content of DAergic receptors in NAc is unknown. The purpose of this study was to investigate whether OrxA can alter gene expression and protein levels of D1R/D2R in NAc. Gene expression was evaluated by real-time PCR analysis and protein levels by western blot in rats. The results show that intracerebroventricular (i.c.v.) injection of OrxA increases both gene transcription and protein content of D2R but fails to modify D1R. This effect was also confirmed with OrxA infusion in NAc/Shell. Our results demonstrate for the first time that OrxA induces up-regulation of gene and protein of D2R in NAc. These findings support the hypothesis that OrxA modulates the DAergic transmission and this may serve to understand how orexin signaling enhances DA responses at baseline conditions and in response to psychostimulants.
Assuntos
Neurônios Dopaminérgicos/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Orexinas/farmacologia , Receptores de Dopamina D1/genética , Receptores de Dopamina D2/genética , Animais , Neurônios Dopaminérgicos/citologia , Neurônios Dopaminérgicos/metabolismo , Regulação da Expressão Gênica , Injeções Intraventriculares , Masculino , Núcleo Accumbens/citologia , Núcleo Accumbens/metabolismo , Orexinas/metabolismo , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Transdução de Sinais , Técnicas EstereotáxicasRESUMO
Objective: Dual diagnosis (DD) is the co-occurrence of at least one substance use disorder and one or more mental disorders in a given individual. Despite this comorbidity being highly prevalent and associated with adverse clinical outcomes, its neurobiology remains unclear. Furthermore, patients with DD are at higher risk for suicidal behavior in comparison with single disorder patients. Our objective was to evaluate brain gene expression patterns in individuals with DD who died by suicide. Methods: We compared the gene expression profile in the dorsolateral prefrontal cortex of suicides with DD (n = 10) to the transcriptome of suicides with substance use disorder alone (n = 10), suicides with mood disorders (MD) alone (n = 13), and suicides without mental comorbidities (n = 5). Gene expression profiles were assessed by microarrays. In addition, we performed a brain cell type enrichment to evaluate whether the gene expression profiles could reflect differences in cell type compositions among the groups. Results: When comparing the transcriptome of suicides with DD to suicides with substance use disorder alone and suicides with MD alone, we identified 255 and 172 differentially expressed genes (DEG), respectively. The overlap of DEG between both comparisons (112 genes) highlighted the presence of common disrupted pathways in substance use disorder and MD. When comparing suicides with DD to suicides without mental comorbidities, we identified 330 DEG, mainly enriched in neurogenesis. Cell type enrichment indicated higher levels of glial markers in suicides with DD compared to the other groups. Conclusions: Suicides with DD exhibited a gene expression profile distinct from that of suicides with a single disorder, being substance use disorder or MD, and suicides without mental disorders. Our results suggest alteration in the expression of genes involved in glial specific markers, glutamatergic and GABAergic neurotransmission in suicides with DD compared to suicides with a single disorder and suicides without mental comorbidities. Alterations in the expression of synaptic genes at different levels were found in substance use disorder and MD.
Assuntos
Perfilação da Expressão Gênica , Transtornos do Humor , Córtex Pré-Frontal/metabolismo , Transtornos Relacionados ao Uso de Substâncias , Suicídio Consumado , Adolescente , Adulto , Alcoolismo/epidemiologia , Alcoolismo/genética , Alcoolismo/metabolismo , Autopsia , Causas de Morte , Comorbidade , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/metabolismo , Diagnóstico Duplo (Psiquiatria) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/epidemiologia , Transtornos do Humor/genética , Transtornos do Humor/metabolismo , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/genética , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Suicídio Consumado/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: Gene expression alterations have been implicated in suicide pathology. However, the study of the regulatory effect of DNA methylation on gene expression in the suicidal brain has been restricted to candidate genes. OBJECTIVE: The objective of the study was to identify genes whose expression levels are correlated with DNA methylation in the prefrontal cortex of suicides. METHODS: Postmortem prefrontal cortex samples from 21 suicides and six non-suicides were collected. Transcriptomic and DNA methylation profiles were evaluated with microarrays; cis correlations between gene expression and CpG methylation were screened. We then analyzed the presence of transcription factor (TF) binding sites (TFBS) at CpG sites correlated with gene expression. Gene expression of TFs involved in neurodevelopmental binding to predicted TFBS was determined in the BrainSpan database. RESULTS: We identified 22 CpG sites whose methylation levels correlated with gene expression in the prefrontal cortex of suicides. Genes annotated to identified CpG sites were involved in neurodevelopment (BBS4, NKX6-2, AXL, CTNND1, and MBP) and polyamine metabolism (polyamine oxidase [PAOX]). Such correlations were not detected in the nonsuicide group. Nine TFs (USF1, TBP, SF1, NRF1, RFX1, SP3, PKNOX1, MAZ, and POU3F2) showed differential expression in pre- and post-natal developmental periods, according to BrainSpan database. CONCLUSIONS: The integration of different omic technologies provided novel candidates for the investigation of genes whose expression is altered in the suicidal brain and their potential regulatory mechanisms.
RESUMO
Genetic factors have been implicated in suicidal behavior. It has been suggested that one of the roles of genetic factors in suicide could be represented by the effect of genetic variants on gene expression regulation. Alteration in the expression of genes participating in multiple biological systems in the suicidal brain has been demonstrated, so it is imperative to identify genetic variants that could influence gene expression or its regulatory mechanisms. In this study, we integrated DNA methylation, gene expression, and genotype data from the prefrontal cortex of suicides to identify genetic variants that could be factors in the regulation of gene expression, generally called quantitative trait locus (xQTLs). We identify 6,224 methylation quantitative trait loci and 2,239 expression quantitative trait loci (eQTLs) in the prefrontal cortex of suicide completers. The xQTLs identified influence the expression of genes involved in neurodevelopment and cell organization. Two of the eQTLs identified (rs8065311 and rs1019238) were previously associated with cannabis dependence, highlighting a candidate genetic variant for the increased suicide risk in subjects with substance use disorders. Our findings suggest that genetic variants may regulate gene expression in the prefrontal cortex of suicides through the modulation of promoter and enhancer activity, and to a lesser extent, binding transcription factors.
Assuntos
Córtex Pré-Frontal/metabolismo , Locos de Características Quantitativas/genética , Suicídio/psicologia , Adulto , Córtex Cerebral/metabolismo , Metilação de DNA/genética , Transtorno Depressivo Maior , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Predisposição Genética para Doença/genética , Humanos , Masculino , Transtornos da Personalidade , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genéticaRESUMO
OBJECTIVE: An obsessive-compulsive disorder (OCD) subtype has been associated with streptococcal infections and is called pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS). The neuroanatomical characterization of subjects with this disorder is crucial for the better understanding of its pathophysiology; also, evaluation of these features as classifiers between patients and controls is relevant to determine potential biomarkers and useful in clinical diagnosis. This was the first multivariate pattern analysis (MVPA) study on an early-onset OCD subtype. METHODS: Fourteen pediatric patients with PANDAS were paired with 14 healthy subjects and were scanned to obtain structural magnetic resonance images (MRI). We identified neuroanatomical differences between subjects with PANDAS and healthy controls using voxel-based morphometry, diffusion tensor imaging (DTI), and surface analysis. We investigated the usefulness of these neuroanatomical differences to classify patients with PANDAS using MVPA. RESULTS: The pattern for the gray and white matter was significantly different between subjects with PANDAS and controls. Alterations emerged in the cortex, subcortex, and cerebellum. There were no significant group differences in DTI measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) or cortical features (thickness, sulci, volume, curvature, and gyrification). The overall accuracy of 75% was achieved using the gray matter features to classify patients with PANDAS and healthy controls. CONCLUSION: The results of this integrative study allow a better understanding of the neural substrates in this OCD subtype, suggesting that the anatomical gray matter characteristics could have an immune origin that might be helpful in patient classification.
Assuntos
Doenças Autoimunes/classificação , Imagem de Tensor de Difusão/normas , Transtorno Obsessivo-Compulsivo/classificação , Infecções Estreptocócicas/classificação , Adolescente , Doenças Autoimunes/diagnóstico por imagem , Doenças Autoimunes/patologia , Criança , Interpretação Estatística de Dados , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Masculino , Análise Multivariada , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/patologia , Infecções Estreptocócicas/diagnóstico por imagem , Infecções Estreptocócicas/patologiaRESUMO
The enzyme nitric oxide synthase has been associated with suicide behavior. NOS1, NOS2 and NOS3 genes are implicated in the production of nitric oxide. However, the association between NOS genes and suicide behavior has not yet been established. To assess the association of Nitric Oxide Synthase (NOS) genes and suicide behavior we performed a systematic review a meta-analysis. We searched articles published in three electronic databases, PubMed, Scopus and Web of Sciences, up to February 2019. We used keywords and combinations "NOS", "NOS1", "NOS2", "NOS3" and "suicide". Only articles that met the inclusion criteria were included. To assess the association between NOS genes and suicide behavior we used allelic, dominant and recessive models, as well as homozygous and heterozygous comparisons. The pooled results showed that rs2682826 of Nitric Oxide Synthase 1 gene (NOS1) increased the risk for suicide attempt in the allelic (OR: 1.34; 95 CI: 1.00-1.78), recessive (OR: 1.45; 95 CI:1.06-1.98) and heterozygous (OR: 1.41; 95 CI: 1.09-1.81) models. We found that the rs2682826 of NOS1 could increase the risk for suicide attempt. However, these results should only be taken as exploratory; more studies are necessary to determine the association between NOS genes and suicide behavior.
Assuntos
Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo I/genética , Polimorfismo de Nucleotídeo Único , Tentativa de Suicídio , Alelos , Estudos de Associação Genética , HumanosRESUMO
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.
Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Povo Asiático/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante , Fatores de Risco , População Branca/genéticaRESUMO
BACKGROUND: Schizophrenia (SCZ) and dementia, often related, are two of the most common neuropsychiatric diseases; epidemiological studies have shown that SCZ patients present a 2-fold increased risk for dementia compared to non-schizophrenic individuals. We explored the presence of rare and novel damaging gene variants in patients diagnosed with late-onset dementia of Alzheimer's type (DAT) or SCZ. METHODS: We included 7 DAT and 12 SCZ patients and performed high-depth targeted sequencing of 184 genes. RESULTS: We found novel and rare damaging variants in 18 genes in these Mexican patients. Carriers of these variants showed extreme phenotypes, including, treatment-resistant SCZ or cognitive decline. Furthermore, we found a variation on ABCC1 as a possible link between psychosis and cognitive impairment. DISCUSSION: As an exploratory analysis, we report some interesting variations that should be corroborated in larger sample size studies.
Assuntos
Doença de Alzheimer/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Demência/fisiopatologia , Esquizofrenia/fisiopatologia , Doença de Alzheimer/genética , Disfunção Cognitiva/genética , Demência/genética , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , México , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Fenótipo , Esquizofrenia/genéticaRESUMO
BACKGROUND: Concurrence of substance use disorders (SUDs) is high in individuals with psychiatric illnesses; more importantly, individuals with both disorders (dual diagnosis) have more severe symptoms. Psychiatric disorders have been proposed to share a genetic susceptibility with SUDs. To explore this shared genetic susceptibility, we analyzed whether any of the polygenic risk scores (PRSs) for psychiatric disorders could be associated to dual diagnosis in patients with schizophrenia (SCZ) or bipolar disorder (BD). METHODS: We included 192 individuals of Mexican ancestry: 72 with SCZ, 53 with BD, and 67 unrelated controls without psychiatric disorders. We derived calculations of PRS for autism spectrum disorders, attention-deficit/hyperactive disorder, BD, major depression, and SCZ using summary genome-wide association statistics previously published. RESULTS: We found that dual diagnosis had a shared genetic susceptibility with major depressive disorder (MDD) and SCZ; furthermore, in individuals with BD, dual diagnosis could be predicted by PRS for MDD. CONCLUSIONS: Our results reinforce the notion that individuals with dual diagnosis have a higher genetic susceptibility to develop both disorders. However, analyses of larger sample sizes are required to further clarify how to predict risks through PRS within different populations.
Assuntos
Transtorno Bipolar/epidemiologia , Transtornos Mentais/epidemiologia , Esquizofrenia/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto , Transtorno Bipolar/genética , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/genética , Diagnóstico Duplo (Psiquiatria) , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Transtornos Mentais/genética , México , Pessoa de Meia-Idade , Esquizofrenia/genética , Transtornos Relacionados ao Uso de Substâncias/genética , Adulto JovemRESUMO
Multiple large-scale studies such as genome-wide association studies (GWAS) have been performed to identify genetic contributors to suicidal behaviors (SB). We aimed to summarize and analyze the information obtained in SB GWAS, to explore the biological process gene ontology (GO) of genes associated with SB from GWAS, and to determine the possible implications of the genes associated with SB in Kyoto encyclopedias of genes and genomes (KEGG) biological pathways. The articles included in the analysis were obtained from PubMed and Scopus databases. Enrichment analyses were performed in Enrichr to evaluate the KEGG pathways and GO of the genes associated with SB of GWAS. The findings of biological process GO analysis showed 924 GO involved in genes related with SB; of those, the regulation of glucose import in response to insulin stimulus, regulation of protein localization to plasma membrane, positive regulation of endopeptidase activity, heterotypic cell-cell adhesion, regulation of cardiac muscle cell contraction, positive regulation of protein localization to plasma membrane, and positive regulation of protein localization to cell periphery biological process GO showed significant statistical association. Furthermore, we obtained 130 KEGG pathways involved in genes related with SB, which Aldosterone synthesis and secretion, Rap1 signaling pathway and arrhythmogenic right ventricular cardiomyopathy pathways showed a significant statistical association. These findings give a better perspective of the biological participation of genes associated with SB, which will be important to perform adequate strategies to prevent and treat SB.