Thelma Beatriz González-Castro

The role of brain‐derived neurotrophic factor (BDNF) Val66Met genetic polymorphism in bipolar disorder: a case–control study, comorbidities, and meta‐analysis of 16,786 subjects

The aim of this study was to evaluate the association of Val66Met brain‐derived neurotrophic factor (BDNF) polymorphism with bipolar disorder in (i) a meta‐analysis and (ii) a case–control study in a Mexican population. We also investigated the possible association of this polymorphism with clinical features.

Association of the 5HTR2A gene with suicidal behavior: CASE-control study and updated meta-analysis

BackgroundThe polymorphism rs6313 (T102C) has been associated with suicidal behavior in case–control and meta-analysis studies, but results and conclusions remain controversial. The aim of the present study was to examine the association between T102C with suicidal behavior in a case–control study and, to assess the combined evidence – this case–control study and available data from other related studies – we carried out a meta-analysis.MethodsWe conducted a case–control study that included 161 patients with suicide attempts and 244 controls; we then performed a meta-analysis. The following models were evaluated in the meta-analysis: A) C allele vs T allele; B) T allele vs C allele; C) Caucasian population, D) Asian population, and E) suicide attempters with schizophrenia.ResultsWe found an association between attempted suicide and control participants for genotype (χ2=6.28, p=0.04, df=2) and allele (χ2=6.17, p=0.01, df=1, OR 1.48 95% IC: 1.08-2.03) frequencies in the case–control study. The meta-analysis, comprising 23 association studies (including the present one), showed that the rs6313 polymorphism is not associated with suicidal behavior for the following comparisons:T allele vs C allele (OR: 1.03; 95% CI 0.93-1.13; p(Z)=0.44); C allele vs T allele: (OR:0.99; 95% CI: 0.90-1.08; p(Z)=0.22); Caucasians (OR:1.09; 95% CI: 0.96-1.23), and Asians (OR:0.96; 95% CI: 0.84-1.09).ConclusionOur results showed association between the rs6313 (T102C) polymorphism and suicidal behavior in the case–control study. However, the meta-analysis showed no evidence of association. Therefore, more studies are necessary to determine conclusively an association between T102C and suicidal behavior.

Association of 5HTR1A gene variants with suicidal behavior: Case-control study and updated meta-analysis

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.

Increase in Suicide Rates by Hanging in the Population of Tabasco, Mexico between 2003 and 2012

Background: Worldwide, the suicide rate is decreasing. To examine changes in the rates of completed suicide in the Mexican population from 2003 to 2012, we analyzed these changes according to: (i) the method of suicide; (ii) age group and (iii) gender. Methods: The data analyzed were obtained from governmental organizations from the State of Tabasco, Mexico. The data provided 1836 cases of subjects born and residing in Tabasco, who completed suicide in this state. Results: Suicide by hanging was a common choice of suicide method for Mexicans. The rate of suicide by hanging increased from 5.80 to 6.49 per 100,000 persons between 2003 and 2012, a rate percentage increase of 11.89%. Conclusions: Hanging was found to be the most common choice of suicide in the Mexican population, probably because the materials required are easily available and the method does not require complicated techniques, especially in the 55–64 age group. Strategies for prevention and intervention should be developed for the Mexican population considering suicide rates by age group and gender.

Study on genes of the serotonergic system and suicidal behavior: protocol for a case-control study in Mexican population.

BackgroundSuicidal behavior is a leading cause of injury and death worldwide. Several studies have provided a possible relationship between genetic factors and suicidal behavior. Also, these studies have shown evidence for altered serotonergic neural transmission in the pathogenesis of suicidal behavior. In addition, genes pertaining to the serotonergic system have been proposed as candidates to establish biological correlates between suicidal behavior and the serotonergic system. The most studied genes are SCL6A4, HTR2A, HTR2C, HTR1A, HTR1B, TPH-1, and TPH-2. To get a comprehensive understanding of the association with suicidal behavior we will conduct genotype assays studies in a Mexican population.Methods/DesignWe will conduct a case–control study. The population sample will comprise adolescent and adult patients admitted for attempted of suicide and diagnosed by a psychiatrist. A peripheral blood sample will be taken from all the subjects (cases and controls). Genomic DNA from the leukocytes blood sample will be extracted. The genotypes of interest are distributed in the following genes: SCL6A4, HTR2A, HTR1A, HTR1B, HTR2C, TPH-2 and TPH-1. All the samples will be analyzed using a polymerase chain reaction (PCR) end-point method. We will evaluate the Hardy-Weinberg Equilibrium. The chi-squared test or Fisher’s exact test will be used to compare genotype and allele frequencies between control and case groups. The Quanto 1.2 software will measure the sample size of the association. For all the association analyses the level of significance will be set at p = 0.05 and the confidence interval at 95%.DiscussionSuicidal behavior has been increase in Mexico, principally in young population. Our study will demonstrate the association between serotoninergic genes and suicide behavior in Mexican population.

Distribution of the Val108/158Met polymorphism of the COMT gene in healthy Mexican population☆

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.

No association between ApoE and schizophrenia: Evidence of systematic review and updated meta-analysis

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) ε4 vs ε3, B) ε4 vs ε2, C) ε4 vs ε3+ε2, 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 ε3 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 ε3 and schizophrenia in the Asian population.

The role of C957T, TaqI and Ser311Cys polymorphisms of the DRD2 gene in schizophrenia: systematic review and meta-analysis

BackgroundThe association between the dopamine D2 receptor (DRD2) gene and schizophrenia has been studied though no conclusive outcomes have been attained. The aim of this study was to perform a systematic review and meta-analysis to explore the relation between three polymorphisms of the DRD2 gene (C957T, TaqI and Ser311Cys) and schizophrenia.MethodsThe search was made in PubMed and EBSCO databases (up to February 2016). The systematic review included 34 case–control association studies (34 for C957T, 16 for TaqI and 36 for Ser311Cys). The association analysis comprised the allelic, additive, dominant, and recessive genetic models. The meta-analysis was performed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement.ResultsThe meta-analysis showed that TaqI (additive model: OR 0.57, 95% CI 0.30–1.14) and C957T (additive model: OR 0.75, 95% OR 0.58–0.97, recessive model: OR 0.79, 95% CI 0.64–0.98) exert a protective effect against developing schizophrenia. However, the sub-analysis for the C957T variant showed that this polymorphism exhibits a risk factor effect on Chinese individuals (allelic model: OR 1.33, 95% CI 1.04–1.70).ConclusionOur meta-analysis suggests an association of the DRD2 gene and the risk for schizophrenia, given that TaqI and C957T polymorphisms presented a protective effect against schizophrenia, and in the sub-analyses the C957T variant increased the risk for this disorder in the Chinese population.

Gender differences in socio-demographic, clinical characteristics and psychiatric diagnosis in/of suicide attempters in a Mexican population

Objective The aim of the present study was to analyse demographic and clinical characteristics, as well as psychiatric diagnoses to identify gender differences in patients with attempted suicide in a Mexican population. Methods Between September 2010 and September 2012, 140 suicide attempts were documented in the Department of Psychiatry at the General Hospital of Comalcalco (Hospital General de Comalcalco in Spanish) in Tabasco, Mexico. Diagnoses were established using the DSM-IV questionnaire in which Axis I and II were considered. The Suicide Intent Scale was also applied. Results In our sample, 63.6% were females and 36.4% males. With regard to socio-demographic characteristics, the predominant marital status in males was single, and in females married (χ2=5.93, df=2, p=0.05). In occupation the male group was mainly unemployed and housewife in females (χ2=55.51, df=4, p<0.001). Male subjects were more likely to consume alcohol (χ2=20.40, df=1, p≤0.001), cannabis (χ2=16.62, df=1, p≤0.001) or tobacco. The prevalence of psychiatric diagnosis was significantly different because, the male group was mainly diagnosed with substance-related disorders, whereas female participants showed a prevalence of stress-related disorders (χ2=34.17, gl=4, p=0.0001). Conclusion Our results provide evidence that the characteristics of suicide attempt are different by gender in the Mexican population. Interventions are necessary for the development of prevention strategies that may lead to a reduction in suicidal behaviour. These preventive activities should consider the occupation for the female group and consumption of alcohol, cannabis or tobacco in the male group.

Association analysis of TPH-1 and TPH-2 genes with suicidal behavior in patients with attempted suicide in Mexican population

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.