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Schizophrenia (SZ) is a mental disorder characterized by neurocognitive dysfunctions and a reduction in occupational and social functioning. Several studies have provided evidence for mitochondrial dysfunction in the pathophysiology of SZ. In this sense, it is known that the addition of genetic variations in mitochondrial DNA (mtDNA) impairs oxidative phosphorylation of enzymatic complexes in mitochondria, resulting in ATP depletion and subsequent enhancement of reactive oxygen species; this is associated with cellular degeneration and apoptosis observed in some neuropsychiatric disorders. As a consequence of mitochondrial dysfunction, an increase in circulating cell-free mtDNA fragments can occur, which has been observed in individuals with SZ. Moreover, due to the bacterial origin of mitochondria, these cell-free mtDNA fragments in blood plasma may induce inflammatory and immunogenic responses, especially when their release is enhanced in specific disease conditions. However, the exact mechanism by which mtDNA could be released into blood plasma is not yet clear. Therefore, the aims of this review article were to discuss the participation of mtDNA genetic variations in physiopathologic mechanisms of SZ, and to determine the status of the disease and the possible ensuing changes over time by using circulating cell-free mtDNA fragments as a biomarker.

Suicidal behavior is result of the interaction of several contributors, including genetic and environmental factors. The integration of approaches considering the polygenic component of suicidal behavior, such as polygenic risk scores (PRS) and DNA methylation is promising for improving our understanding of the complex interplay between genetic and environmental factors in this behavior. The aim of this study was the evaluation of DNA methylation differences between individuals with high and low genetic burden for suicidality. The present study was divided into two phases. In the first phase, genotyping with the Psycharray chip was performed in a discovery sample of 568 Mexican individuals, of which 149 had suicidal behavior (64 individuals with suicidal ideation, 50 with suicide attempt and 35 with completed suicide). Then, a PRS analysis based on summary statistics from the Psychiatric Genomic Consortium was performed in the discovery sample. In a second phase, we evaluated DNA methylation differences between individuals with high and low genetic burden for suicidality in a sub-sample of the discovery sample (target sample) of 94 subjects. We identified 153 differentially methylated sites between individuals with low and high-PRS. Among genes mapped to differentially methylated sites, we found genes involved in neurodevelopment (CHD7, RFX4, KCNA1, PLCB1, PITX1, NUMBL) and ATP binding (KIF7, NUBP2, KIF6, ATP8B1, ATP11A, CLCN7, MYLK, MAP2K5). Our results suggest that genetic variants might increase the predisposition to epigenetic variations in genes involved in neurodevelopment. This study highlights the possible implication of polygenic burden in the alteration of epigenetic changes in suicidal behavior.

Psychiatric disorders are complex polygenic diseases that show common genetic vulnerability. Several studies have investigated the association of polymorphisms of FK506 binding protein 51 (FKBP5) gene and depressive disorders or suicidal behavior, however, the results have been controversial and ambiguous. The aim of our study was to explore the role of the FKBP5 gene variants (rs1360780, rs3800373 and rs4713916), in depressive disorders or suicidal behavior through a systematic review and a meta-analysis. The protocol number of the study is PROSPERO CRD42018089295. The meta-analysis included 12 studies. Odds ratios with 95% confidence intervals were used to evaluate the association and the publication bias was tested by Egger's test and funnel plot; heterogeneity was assessed by the Cochran's chi-square-based Q statistic test and the inconsistency index. Our results showed that the rs3800373 and rs4713916 were associated with an increased risk of depressive disorders when using the heterozygous and dominant models. In the stratified analysis by ethnicity, a significantly increased risk of depressive disorders was also observed for rs3800373 and rs4713916 in Caucasians. When we analyzed suicidal behavior, we found a significant association with the rs1360780 of FKBP5 and suicidal behavior risk in the overall population and rs3800373 in completed suicide subgroup. Existing evidence indicates that the polymorphisms of FKBP5 gene are associated with risk of depressive disorders and suicidal behavior. Future studies with larger sample sizes will be necessary to confirm the present results.

Resumen Introduccion y objetivo Multiples estudios han encontrado una relacion directa entre las concentraciones de leptina y la actividad de la enfermedad en artritis reumatoide. Pacientes y metodos Se estudiaron 77 pacientes con artritis reumatoide, la determinacion de la leptina fue a traves de inmunoanalisis enzimatico. Se evaluo la actividad de la enfermedad mediante el DAS-28 PCR. Se realizo un modelo de regresion logistica multivariante para determinar la asociacion entre las variables significativas y las concentraciones de leptina. Resultados El 40,3% de los pacientes estaban en remision, el 41,6% actividad leve, el 11,7% actividad moderada y el 6,5% actividad grave. Se encontro una relacion independiente entre mayores concentraciones de leptina y la actividad de la enfermedad (RR 1,7; IC al 95%: 1,4-3,2; p = 0,03), el numero de articulacion tumefactas (RR 4,6; IC al 95%: 1,7-8,3; p = 0,000), el numero de articulaciones dolorosas (RR 3,4; IC al 95%: 1,6-4,6; p = 0,000) y a presencia de sindrome metabolico (RR 1,3; IC al 95%: 1,2-1,9; p = 0,045). Conclusiones Los datos obtenidos sugieren que la leptina serica esta elevada en pacientes con AR activa.

Suicide is a serious worldwide health problem of critical consequences. Nowadays genetic factors are considered to be an important cause of suicide. The association between Val66Met (rs6265) polymorphism of the BDNF gene and suicide behavior has been increasingly studied. The aim of this study was to perform a meta-analysis in order to unravel the possible association between BDNF gene Val66Met polymorphism and suicide behavior. These meta-analysis and systematic review were performed using 23 articles that searched for a genetic association between Val66Met and suicide behavior, including 4532 cases and 5364 control subjects. The association was analyzed following the models: allelic, homozygous, heterozygous, dominant and recessive. Also, analyses by ethnicity (Caucasian and Asian populations) were done following the same four models. When the overall population was evaluated, we found no evidence of association between the polymorphism Val66Met of BDNF (rs6265) and suicide behavior (Met vs. Val: OR: 1.01; 95% CI = 0.92–1.10). However, a significant increased risk was found in the subgroup analysis by ethnicity in Caucasian populations (Met-Met vs. Met-Val + Val-Val: OR: 1.96; 95% CI = 1.58–2.43) and Asian populations (Val-Val vs. Val-Met + Met: OR: 1.36; 95% CI = 1.04–1.78). Our results suggest there is no association between the BDNF gene Val66Met (rs6265) and suicide behavior in the overall population. However, ethnic differences can be observed and the BDNF Val66Met might increase the risk for suicide behavior in Asian and Caucasian populations. Further studies with larger samples are necessary in order to have conclusive outcomes.

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

Objective Using the method of psychological autopsy, we identified differences by gender in socio-demographic aspects, signs and symptoms, and suicide characteristics in a population of the state of Tabasco. Mexico. Methods Between the years 2007–2014, 182 psychological autopsies were documented by the Secretary of Health of the State of Tabasco, Mexico. A structured questionnaire was used to obtain information on socio-demographic aspects and suicide characteristics. Results The sample was mainly formed by males (78%). 84% of the sample used hanging as suicide method. However, in comparison with the male group, females were older on the average (p = 0.002); they were mostly housewives (37.5%) and had more years of schooling (p = 0.004). Other significant differences predominantly present in the male group were: the use of alcohol at the time of suicide (52.1%), job retirement, and increases in apathy (50.7%) and aggressiveness (36.6%) (p Conclusion Our results suggest that there are differences by gender between subjects with completed suicide. Factors such as alcohol consumption, job retirement, aggressiveness and isolation/social apathy certainly render men more vulnerable to suicide in the Mexican population.

Introduction Schizophrenia affects between 0.3% and 2% of the worldwide population. A genetic contribution has been postulated in the development of this disorder. Genes such as ApoE have been implicated in the neurodevelopment associated with schizophrenia in case–control and meta-analysis studies, but the results remain inconclusive. Due to this, the aim of the present study was to explore the association between ApoE and schizophrenia through a meta-analysis. Material and methods We collected all relevant studies by searching PubMed and EBSCO databases. The pooled odds ratios with 95% confidence intervals were calculated to estimate the association. The following models were evaluated: A) e4 vs e3, B) e4 vs e2, C) e4 vs e3 + e2, D) Caucasian population and E) Asian population. Statistical analyses were performed using EPIDAT 3.1 software. Results The meta-analyses comprised 28 association studies, which included 4703 controls and 3452 subjects with schizophrenia. A significant protective effect was found for allele e3 in the Asian population (OR = 0.73, 95% CI = 0.54–0.98). No significant associations were observed in the other models and populations analyzed. Conclusions Our meta-analysis suggests a protective association between ApoE allele e3 and schizophrenia in the Asian population.

Cortisol can be considered as one biomarker for diagnosis of suicide; nevertheless, several studies have shown conflicting results. This study aimed to evaluate the levels of cortisol in individuals with suicide behavior and controls (healthy or with other psychiatric disorders). Published articles were searched on online databases (PubMed, Scopus and EBSCO). Standardized mean differences (SMD), heterogeneity, publication bias and sensitivity were assessed using the Comprehensive Meta-Analysis (CMA) statistical software. The meta-analysis comprised 30 studies that provided 1775 cases, and 2162 controls (696 healthy individuals and 1465 individuals with other psychiatric diagnoses). The pooled results revealed that cortisol levels were higher in individuals with suicide behavior (SMD = 0.92, 95%CI = 0.26; 1.57, P = 0.006; I2 = 88%, Q

Background Suicidal behavior is a worldwide health problem. Tryptophan hydroxylase (TPH) is a rate limiting enzyme in the biosynthesis of serotonergic neurotransmission. TPH-1 and TPH-2 genes encode for TPH isoforms and have been implicated as candidate genes for suicidal behavior. The aim of this study was to evaluate the association between the genetic variants of the TPH-1 (rs21102 and 1607395) and TPH-2 (rs4290270, rs7305115 and rs1007023) genes and suicidal behavior in a Mexican population. Methods We conducted a case-control study including 200 cases with suicide attempt and 263 controls. Patients were evaluated by a trained psychiatrist or clinical psychologists. Five polymorphisms were genotyped and assessed for allele, genotype and haplotype association with suicide attempt. Results The rs7305115 polymorphism of the TPH-2 gene was associated with suicidal behavior in a Mexican population in genotype ( χ 2 =6.02, df =2, p =0.04) and allele (OR=1.39, 95%IC=1.06–1.81, p =0.01) frequencies. The THP-2 haplotypes GTA ( χ 2 =5.68, p =0.01) and ATT ( χ 2 =5.0, p =0.02) were associated with risk for suicide attempt. Conclusion Our results provide evidence for an association between the rs7305115 polymorphism of the TPH-2 gene and suicidal behavior in a Mexican population. However, more studies are necessary to replicate these results using larger samples.

Nephrolithiasis is a complex disease in which its pathophysiology is strongly influenced by genetics. Polymorphisms of the vitamin D receptor (VDR) gene have been reported to be associated with the development of kidney stones which in most cases are composed predominantly of calcium salts. For the purpose of this study, we performed a systematic review and meta-analysis to analyze the association of BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236) and FokI (rs2228570) polymorphisms with nephrolithiasis. A systematic search was performed up to June 2018 using PubMed, Embase and ISI Web of Knowledge databases. The keywords used for the search were “vitamin D receptor or VDR” and “polymorphisms or SNPs” combined with “urolithiasis or nephrolithiasis”. A meta-analysis was performed with the results of the selected and included studies. After analyzing 23 publications, we observed that BsmI polymorphism (rs1544410) has a protective association against nephrolithiasis (Allelic model: OR = 0.84, CI 95% 0.73–0.96, Z p-value 0.015; homozygous model: OR = 0.72, CI 95% 0.54–0.97, Z p-value 0.033). Furthermore, we observed that FokI polymorphism (rs2228570) has a decreased risk of nephrolithiasis in the heterozygous model in the presence of heterogeneity (OR = 0.69, CI 95% 0.48–0.99, Z p-value 0.044), as well as in the absence of heterogeneity (OR = 0.81, CI 95% 0.66–0.99, Z p-value 0.045). Additionally, TaqI polymorphism (rs731236) was associated with a decreased risk of nephrolithiasis in the heterozygous model (OR = 0.77, CI 95% 0.63–0.94, Z p-value 0.010), and no overall association was observed with ApaI polymorphism (rs7975232). This meta-analysis provided comprehensive evidence that VDR polymorphisms are associated with upper urinary tract stones incidence and the genetic variants we studied provide protection against nephrolithiasis.

Introduction The gene encoding the serotonin 1A receptor (5HTR1A) has been a candidate gene associated with suicidal behavior in case-control and meta-analysis studies. We carried out a meta-analysis and a case-control study on the 5HTR1A gene to examine the association of this gene with suicidal behavior. Methods We performed a systematic search in electronic databases to study meta-analytically the association of 5HTR1A gene with suicidal behavior; we found 9 published genetic association studies concerning the rs6295 polymorphism. To get a comprehensive knowledge of this association we conducted a case-control study on the following polymorphisms: rs1423691, rs6295, and rs878567 in a Mexican population; the sample was composed of 152 suicide attempters and 264 healthy subjects. Results The meta-analysis revealed that the rs6295 polymorphism is not associated with suicidal behavior. Similarly, no significant association for polymorphisms rs6295 and rs878567 was found in the case-control study. The polymorphism rs1423691 was excluded of the association analysis because cases and control groups were in Hardy–Weinberg disequilibrium. Conclusion The meta-analysis of functional rs6295 polymorphisms produced no association. Likewise, the analysis in our case-control study in a Mexican population resulted in lack of association of polymorphisms rs6295 and rs878567 with suicidal behavior. However, further studies assessing different populations, as well as larger samples are necessary to obtain conclusive outcomes.

Catechol-O-methyltransferase (COMT) inactivates the catecholamines adrenaline, noradrenaline and dopamine. On the other hand, some studies have reported that the enzymatic activity of COMT is partly genetically determined. With regard to the COMT gene, the most studied polymorphism is the functional variant Val108/158Met (rs4680), which results in substantial three- to four-fold variations in enzyme activity. To date, the rs4680 polymorphism of COMT has been associated with a number of disorders. In addition, this polymorphism has been found to have important differences in frequency according to the studied population. Therefore, the aim of the present study was to evaluate the frequency of a common single nucleotide polymorphism (SNP) Val108/158Met of the COMT gene in the Mexican population. Accordingly, we recruited 431 healthy volunteers. Our sample consisted of 111 healthy individuals from Mexico City and 320 individuals from the state of Tabasco, Mexico. We observed that Met was the most common allele, ranging from 57% (Tabasco) to 85% (Mexico City). In addition, we analyzed the frequency of Val108/158Met polymorphism of Caucasian (54% Met allele), Asian (29% Met allele) and African (34% Met allele) populations separately and also in comparison with Mexican (63% Met allele) population. In conclusion, the distribution of the Val108/158Met polymorphism distinguishes the Mexican population studied from other populations, but it is necessary to increase the size of the sample to get more conclusive results.

The purpose of this study was to assess the effect of the non-selective cholecystokinin receptor antagonist proglumide on the antinociceptive activity of ketorolac and meloxicam in non-diabetic and diabetic rats. Streptozotocin (60 mg/kg) injection caused hyperglycemia which was maintained for 2 weeks. Formalin-evoked flinching was increased in diabetic rats as compared to non-diabetic rats. Local peripheral ipsilateral, but not contralateral, administration of ketorolac and meloxicam produced antinociception in non-diabetic and diabetic rats. However, the antinociceptive effect of both drugs was significantly reduced in diabetic animals. Proglumide was ineffective by itself and it did not affect the antinociception induced by the cyclooxygenase inhibitors in non-diabetic rats. Contrariwise, proglumide reduced formalin-induced nociception and it increased ketorolac- or meloxicam-induced antinociception in diabetic rats. These results suggest that peripheral cholecystokinin plays an important role in diabetes-induced sensitization as well as in the reduction of the antinociceptive effects of ketorolac and meloxicam in diabetic rats. The combination of cholecystokinin receptor antagonists and ketorolac or meloxicam may be a useful strategy to reduce nociception in diabetic patients.