Beatriz Elena Camarena - Academia.edu (original) (raw)
Papers by Beatriz Elena Camarena
Psychiatric Genetics, 1998
CNS spectrums, May 1, 1999
Genetic study holds potential for understanding the etiology of a number of serious psychiatric d... more Genetic study holds potential for understanding the etiology of a number of serious psychiatric disorders. In the case of obsessive-compulsive disorder (OCD), many investigators agree that there is a strong genetic component to its development. In this article, we review the scientific evidence gleaned from different types of studies that has led to a better understanding of the nature of the inherited factors in OCD.
International Journal of Environmental Research and Public Health
There is little recent information about the prevalence of symptomatology of mental health disord... more There is little recent information about the prevalence of symptomatology of mental health disorders in representative population samples in Mexico. To determine the prevalence of mental health symptoms in Mexico and its comorbidity with tobacco, alcohol, and drug use disorder (SUD), we used the 2016–17 National Survey of Drug, Alcohol, and Tobacco Use (Encuesta Nacional de Consumo de Drogas, Alcohol y Tabaco, ENCODAT 2016–2017). The data were collected from households using a cross-sectional, stratified, multistage design, with a confidence level of 90% and a response rate of 73.6%. The final sample included 56,877 completed interviews of individuals aged 12–65, with a subsample of 13,130 who answered the section on mental health. Symptoms of mania and hypomania (7.9%), depression (6.4%), and post-traumatic stress (5.7%) were the three main problems reported. Of this subsample, 56.7% reported using a legal or illegal drug without SUD, 5.4% reported SUD at one time on alcohol, 0.8% ...
Frontiers in Psychiatry
Recent studies suggest that the endocannabinoid system could play an important role in the physio... more Recent studies suggest that the endocannabinoid system could play an important role in the physiopathology of obsessive-compulsive disorder (OCD). There are reports of effective treatment with derivatives of tetrahydrocannabinol (THC). The study of the genetic factor associated with psychiatric disorders has made possible an exploration of its contribution to the pharmacological response. However, very little is known about the genetic factor or the prevalence of cannabis use in the Mexican population with OCD. The objective of this study is to compare the prevalence of use and dependence on cannabis in individuals with obsessive-compulsive symptomatology (OCS) with that of individuals with other psychiatric symptoms (psychosis, depression, and anxiety), and to explore the association between genetic risk and use. The study includes a total of 13,130 individuals evaluated in the second stage of the 2016 National Survey of Drug, Alcohol, and Tobacco Use (Encodat 2016), with genetic a...
RESUMEN. En este estudio de asociacion de las variantes geneticas del transportador para serotoni... more RESUMEN. En este estudio de asociacion de las variantes geneticas del transportador para serotonina, los rasgos de la personalidad, la agresion explicita y el nivel de impulsividad en pacientes con antecedentes de intentos suicidas y de sus familiares de 1er grado, se incluyeron pacientes que acudieron al Servicio de Consulta Externa, preconsulta y hospitalizacion del INPRF con antecedentes de intentos suicidas y que ademas contaron en eje I con el diagnostico psiquiatrico de algun trastorno afectivo sin comorbilidad, encontrando una asociacion entre las alteraciones del sistema serotoninergico, los rasgos de personalidad, la agresividad y el nivel de impulsividad, con la manifestacion de comportamientos suicidas, debera aclararse el significado de dicha asociacion. Palabras clave: Suicidio, agresividad, sistema serotoninergico.
Gene, 2021
BACKGROUND Neurocognitive disorders (NCDs) are characterized by cognitive decline. Most genetic s... more BACKGROUND Neurocognitive disorders (NCDs) are characterized by cognitive decline. Most genetic studies of NCDs have been focused on single-nucleotide polymorphism; other genetic variations, such as copy number variants (CNV), have been less explored. The aim of the present study was to explore CNVs associated with NCDs in a small sample of Mexican individuals and search for the frequency in a larger replication sample of individuals at high risk for or diagnosed with NCDs. METHOD The exploratory analysis analyzed whole-genome CNVs associated with NCDs in 1335 individuals, of whom 35 were diagnosed with NCDs and 1300 were population-based controls. Whole-genome CNVs were derived from PsychArray and the PennCNV algorithm. The frequency of associated CNVs in a sample of 277 individuals diagnosed with NCDs and 70 high-risk individuals was then determined using RT-PCR. RESULTS The exploratory analysis identified one deletion associated with NCDs (p = 0.007) affecting the gene MGAT4C (Mannosyl (Alpha-1,3-)-Glycoprotein Beta-1,4-N-Acetylglucosaminyltransferase, Isozyme C). In the replication sample, a frequency of 3.97% was found in individuals diagnosed with NCDs and 1.43% in high-risk individuals. CONCLUSIONS An association between a rare CNV on MGAT4C and cognitive impairment was found in this sample of the Mexican population. Nevertheless, studies with larger sample sizes are needed in order to further explore the association.
Frontiers in Pharmacology, 2020
the lowest allele frequency of Group 1. The reduction in these alleles reduces the risk of toxici... more the lowest allele frequency of Group 1. The reduction in these alleles reduces the risk of toxicity from anticancer and antihypercholesterolemic drugs. Our analysis identified different admixture patterns and described how they could be used to refine the practice of pharmacogenetic counseling for this admixed population.
Molecular Psychiatry, 2017
Two obsessive-compulsive disorder (OCD) genome-wide association studies (GWASs) have been publish... more Two obsessive-compulsive disorder (OCD) genome-wide association studies (GWASs) have been published by independent OCD consortia, the International Obsessive-Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and the OCD Collaborative Genetics Association Study (OCGAS), but many of the top-ranked signals were supported in only one study. We therefore conducted a meta-analysis from the two consortia, investigating a total of 2688 individuals of European ancestry with OCD and 7037 genomically matched controls. No single-nucleotide polymorphisms (SNPs) reached genome-wide significance. However, in comparison with the two individual GWASs, the distribution of P-values shifted toward significance. The top haplotypic blocks were tagged with rs4733767 (
European Neuropsychopharmacology, 2017
Background The efficacy of antipsychotics treatment in schizophrenia patients has long been estab... more Background The efficacy of antipsychotics treatment in schizophrenia patients has long been established; however, clinical response to these drugs is not the same in all patients. Genetic variability has been proposed as the main reason for the different outcomes.The dopaminergic pathways, the principal mechanism of action of the antipsychotics, have been the main focus of pharmacogenetic studies in schizophrenia. Some functional single nucleotide polymorphisms (SNPs) have been associated with dopamine disposition or dopamine receptor expression, modifying the response to treatment. The aim of the study was to analyze the association between two response phenotypes (patients with response and resistant) and COMT (Val58Met), DRD2 (A-241G, C/G exon 8, C939T, Taq1A) and DRD3 (Ser9Gly) gene polymorphisms. Methods Treatment response was retrospectively/prospectively assessed. First, we gathered all reliable antipsychotics assays from medical files and through interviews with attending physicians. If these data were not conclusive, a mandatory follow-up period was added with regularly scheduled ratings (using the Positive and Negative Symptom Scale PANSS and the Functional Assessment Scale for Comprehensive Treatment of Schizophrenia FACT-Sz).Treatment response was defined on a ≥ 30% decrease on the total PANSS score (with an antipsychotic different from clozapine). The sample was classified in two main phenotypes: 95 patients on response to treatment group and 81 on resistant-to-treatment group. The genotyping of the COMT (Val58Met), DRD2 (A-241G, C/G exon 8, C939T, Taq1A), and DRD3 (Ser9Gly) gene polymorphisms was performed with allelic discrimination, using TaqMan assays. Differences in genotypes and allele frequencies between the phenotypes of patients were calculated using the X2 test. Also, we performed a logistic regression analysis to predict the likelihood of the resistance-to-treatment phenotype. Results Analysis of Val158Met/COMT showed differences between the response and the resistance groups. The GG genotype (Val/Val) was more frequent in the response group than the resistance group (47% vs. 33%, X2=6.26, 2 df , p=0.04). We also found allele differences between groups (X2=6.65, 1 df, p<0.01). The Val allele was more frequent in the response group (65%) than the resistance. There were no significant associations of DRD2 (A-241G, C/G exon 8, C939T, Taq1A) or the DRD3 (Ser9Gly) SNPs with any of the phenotypes. The logistic regression model showed that the COMT/Val158Met (Met/Met) and DRD3 Ser9Gly (CT) genotypes were predictive for the resistant-to-treatment phenotype, classifying correctly 66% of them (β Exp=1.99, 1.086-3.66 CI 95%, p=0.02). Discussion The COMT/Val158Met SNP (Val/Val) was associated with the response to treatment phenotype. This finding is consistent with the antipsychotics proposed mechanism of action. The antipsychotic efficay on lowering the hyperdopaminergic state would be greater in those patients with the high-activity COMT genotype. The DRD2 SNPs analysis, the main target of several studies, did not show any significant association with the phenotypes. The COMT and DRD3 gene analyses
Salud mental, 2016
Resumen Introducción. La obesidad es la acumulación excesiva de grasa corporal, lo que condiciona... more Resumen Introducción. La obesidad es la acumulación excesiva de grasa corporal, lo que condiciona una alta comorbilidad. El consumo descontrolado de alimentos hipercalóricos es causa de su desarrollo; ésta es una conducta de características similares a la de pacientes con adicción a sustancias. La escala de adicción a los alimentos, YFAS (Yale Food Addiction Scale), permite identificar a sujetos con conducta adictiva a los alimentos. Objetivo. Validar la escala YFAS en español en una muestra de población mexicana adulta. Método. La muestra de participantes (160) respondió a la encuesta en dos ocasiones, con un período de tres semanas entre cada aplicación. La pertinencia de un modelo factorial se corroboró con las pruebas de esfericidad de Bartlett y la medición del parámetro de Kaiser-Meyer-Olkin. Resultados. El α de Cronbach = 0.7963 corroboró la consistencia interna de la escala. Para la confiabilidad se obtuvo el coeficiente de Spearman por la metodología test-retest, de r = 0.5...
Journal of the American Academy of Child & Adolescent Psychiatry, 2016
The inclusion of disruptive mood dysregulation disorder (DMDD) in the DSM-5 has generated a chang... more The inclusion of disruptive mood dysregulation disorder (DMDD) in the DSM-5 has generated a change in the paradigm of the study of chronic irritability in particular in relation to the ODD. Working groups of the ICD-11 have associated chronic irritability with dimension (or subtype) of ODD. The construct of ODD has been described with the presence of two factors with different projections to the future: the factor "irritable" and the factor "headstrong". The aim of the research was to determine the possible association between attachment styles and gene polymorphisms of the serotonin transporter with factors of ODD. Methods: The sample consists in 100 adolescent patients of the National Institute of Psychiatry in Mexico City. Patients who met criteria for ODD were invited. The parent answered the affective reactivity index (IRA) version for parents to measure chronic irritability and the Composite International Diagnostic Interview (CIDI) for ODD symptoms. The patient answered the experience in close relationship Rating Scale (ECR-RS) to measure "avoidance" and "anxiety" in relationships with parents and best friend, IRA version for subject and the CIDI. The best clinical estimate was determined for IRA and CIDI. It was taken a sample of buccal cell for genotyping the gene HTTLPR-5, which it was performed by real-time PCR. Results: 56 percent was female, mean age 15.27, 65 percent showed mixed symptoms of ODD, 24 percent showed "headstrong" symptoms and 11 percent showed "irritable" symptoms. 27 percent of the sample showed secure attachment style, 40 percent were preoccupied, 18 percent avoidant and 15 percent fearful attachment. 34 percent of the sample presents the genotypic variation (SS), 48 percent was (SL) and 14 percent (LL). No significant differences were found between subtypes of ODD and allelic gene frequencies or with attachment styles. Association was found between fearful attachment (x2¼7.8; p ¼ 0.05); heterozygote SL (x2 ¼ 06.0; p ¼ 0.03); mixed symptomatic dominance ODD (p ¼ 0.001); and comorbid diagnoses of PTSD (p ¼ 0.02) in patients with highest score of chronic irritability. Conclusions: Patients with ODD have a higher proportion of insecure attachment styles when compared to the general population. Patients with fearful attachment style were those with higher irritability while they were in the "irritable" and "mixed" category of ODD. A high prevalence of polymorphism S in the sample of patients with ODD was found.
Salud Mental, 2014
Suicide is a common cause of death in adolescents, being mainly associated with depression. In ad... more Suicide is a common cause of death in adolescents, being mainly associated with depression. In addition, the "SS" genotype and the "S" allele of 5-HTTLPR polymorphism of SLC6A4 gene of serotonin transporter have been associated with suicidal behavior. The aims of the present study were to compare the frequency of the polymorphism of SLC6A4 gene in depressed adolescents with and without history of suicidal attempt and to determine if the "SS" genotype was associated with specific clinical features. Method The study examined 53 adolescents who were evaluated with the Diagnostic Interview Schedule for Affective Disorders and Schizophrenia for school-aged children-present and lifetime version (K-SADS-PL). A DNA sample was obtained and 5HTTLPR polymorphisms of SLC6A4 gene were analyzed. Results There were no differences in the frequency of genotype and allele frequencies between groups. However, patients with the "SS" genotype reported a higher frequency of hopelessness and a greater number of suicide attempts. Conclusions The frequency of "SS" genotype did not differ between patients with and without suicidal behavior, but patients with this genotype exhibited differences in clinical features of depression which need further study.
RESUMEN Los estudios de asociación alélica en esquizofrenia se han enfocado en diversas regiones ... more RESUMEN Los estudios de asociación alélica en esquizofrenia se han enfocado en diversas regiones cromosómicas, las cuales contienen genes que codifican para receptores dopaminérgicos. Dentro de éstas, los polimorfismos del gen del receptor de dopamina D4 (DRD4) han sido ampliamente relacionados con la sintomatología psiquiátrica. Existen algunos reportes de asociaciones entre el polimorfismo 48-bp-VNTR en el exón III y la esquizofrenia, aunque esta relación aún es controvertida. La mayoría de los estudios han utilizado pacientes compara-dos contra controles o familias tipo tríos. Sin embargo, no se han presentado estudios con este polimorfismo usando familias con varios afectados. En este estudio se analizó este polimorfismo VNTR del exón III del DRD4 en 60 familias con al menos un par de hermanos afectados. Los datos se analizaron con el programa SIBPAL (software S.A.G.E). La estimación promedio de alelos compartidos fue de 0.54 (p=0.014) y la proporción estimada de parejas de herm...
Molecular psychiatry, 1996
We performed an association analysis of the DRD2, DRD3 and 5HT2A genes polymorphisms in 67 Obsess... more We performed an association analysis of the DRD2, DRD3 and 5HT2A genes polymorphisms in 67 Obsessive-Compulsive Disorder (OCD) patients and 54 healthy controls. There were no statistically significant differences in genotype or allele frequencies for any of the polymorphisms studied between OCD subjects and controls. For the subgrouped analysis, no results were significant after correction for multiple testing, although homozygosity of DRD2/A2A2 in subjects displaying vocal or motor tics approached significance compared to controls (Fisher exact test, P = 0.008). Our results may follow the notion that OCD patients with tics represent a different genetic subtype of the disease.
Revista de investigación clínica; organo del Hospital de Enfermedades de la Nutrición
This investigation reports an association study with alleles of the dopaminergic system genes (ty... more This investigation reports an association study with alleles of the dopaminergic system genes (tyrosine hydroxylase (TH), D2 and D4 receptors) in schizophrenic patients and non-schizophrenic subjects. The genotypes were typed using a polymerase chain reactions PCR-based CA repeat polymorphisms. There were no significant associations between the studied alleles and schizophrenia. Also, a linkage analysis was performed using the same genes (TH, D2 and D4) in two multiple affected schizophrenic families. There was no linkage among any of three genes and schizophrenia. The maximum lod score (Z = 0.43, theta = 0.10 penetrance 100%) was for the tyrosine hydroxylase gene. Linkage analysis significantly excluded the D2 receptor gene (Z = 5.6, theta = 0.01), assuming an autosomal dominant pattern and complete penetrance, However, when the lod scores were calculated with other penetrance values, they lost significance.
Actas españolas de psiquiatría
The aim of the present study was to assess the association between the serotonin transporter gene... more The aim of the present study was to assess the association between the serotonin transporter gene and the Temperament and Character Inventory (TCI) personality dimensions in subjects without psychopathology. Fifty seven individuals without psychiatric symptoms were assessed with the SCL-90, and the TCI. In all subjects a peripheral blood sample was taken to determine their genotypes, after informed consent. Three groups were formed according to the 5-HTT genotype: SS, SL and LL, and the TCI results were compared. There was no association among the 5-HTT genotypes and any of the TCI subscales. There were also no statistical differences among any of the three groups divided by genotype only according to the TCI scores, as well as when compared with historical controls. These results are consistent with other studies that have not found associations among the different measurements of personality and 5-HTT genotypes. Likewise, our data suggest that our sample can be useful as a source ...
Salud Mental, 1998
Resumen En este trabajo se reportan los resultados de un estudio paralelo al proyecto de eficacia... more Resumen En este trabajo se reportan los resultados de un estudio paralelo al proyecto de eficacia y seguridad de la f luvoxamina vs imipramina en el tratamiento de la depresión mayor, El estudio fue doble ciego, controlado y multicéntrico, y se ana-
Molecular Psychiatry, 2013
European Neuropsychopharmacology, 2013
Obsessive-compulsive disorder (OCD) is a psychiatric disorder whose etiology is not yet known. We... more Obsessive-compulsive disorder (OCD) is a psychiatric disorder whose etiology is not yet known. We investigate the role of three variants of the BDNF gene (rs6265, rs1519480 and rs7124442) by single SNP and haplotype analysis in OCD Mexican patients using a case-control and family-based association design. BDNF gene variants were genotyped in 283 control subjects, 232 OCD patients and first degree relatives of 111 OCD subjects. Single SNP analysis in case-control study showed an association between rs6265 and OCD with a high frequency of Val/Val genotype and Val allele (p=0.0001 and p=0.0001, respectively). Also, genotype and allele analysis of rs1519480 showed significant differences (p=0.0001, p=0.0001; respectively) between OCD and control groups. Haplotype analysis showed a high frequency of A-T (rs6265-rs1519480) in OCD patients compared with the control group (OR=2.06 [1.18-3.59], p=0.0093) and a low frequency of haplotype A-C in the OCD patients (OR=0.04 [0.01-0.16], p=0.000002). The family-based association study showed no significant differences in the transmission of any variant. Our study replicated the association between BDNF Val66Met gene polymorphism and OCD. Also, we found a significant association of rs1519480 in OCD patients compared with a control group, region that has never been analyzed in OCD. In conclusion, our findings suggest that BDNF gene could be related to the development of OCD.
Psychiatric Genetics, 1998
CNS spectrums, May 1, 1999
Genetic study holds potential for understanding the etiology of a number of serious psychiatric d... more Genetic study holds potential for understanding the etiology of a number of serious psychiatric disorders. In the case of obsessive-compulsive disorder (OCD), many investigators agree that there is a strong genetic component to its development. In this article, we review the scientific evidence gleaned from different types of studies that has led to a better understanding of the nature of the inherited factors in OCD.
International Journal of Environmental Research and Public Health
There is little recent information about the prevalence of symptomatology of mental health disord... more There is little recent information about the prevalence of symptomatology of mental health disorders in representative population samples in Mexico. To determine the prevalence of mental health symptoms in Mexico and its comorbidity with tobacco, alcohol, and drug use disorder (SUD), we used the 2016–17 National Survey of Drug, Alcohol, and Tobacco Use (Encuesta Nacional de Consumo de Drogas, Alcohol y Tabaco, ENCODAT 2016–2017). The data were collected from households using a cross-sectional, stratified, multistage design, with a confidence level of 90% and a response rate of 73.6%. The final sample included 56,877 completed interviews of individuals aged 12–65, with a subsample of 13,130 who answered the section on mental health. Symptoms of mania and hypomania (7.9%), depression (6.4%), and post-traumatic stress (5.7%) were the three main problems reported. Of this subsample, 56.7% reported using a legal or illegal drug without SUD, 5.4% reported SUD at one time on alcohol, 0.8% ...
Frontiers in Psychiatry
Recent studies suggest that the endocannabinoid system could play an important role in the physio... more Recent studies suggest that the endocannabinoid system could play an important role in the physiopathology of obsessive-compulsive disorder (OCD). There are reports of effective treatment with derivatives of tetrahydrocannabinol (THC). The study of the genetic factor associated with psychiatric disorders has made possible an exploration of its contribution to the pharmacological response. However, very little is known about the genetic factor or the prevalence of cannabis use in the Mexican population with OCD. The objective of this study is to compare the prevalence of use and dependence on cannabis in individuals with obsessive-compulsive symptomatology (OCS) with that of individuals with other psychiatric symptoms (psychosis, depression, and anxiety), and to explore the association between genetic risk and use. The study includes a total of 13,130 individuals evaluated in the second stage of the 2016 National Survey of Drug, Alcohol, and Tobacco Use (Encodat 2016), with genetic a...
RESUMEN. En este estudio de asociacion de las variantes geneticas del transportador para serotoni... more RESUMEN. En este estudio de asociacion de las variantes geneticas del transportador para serotonina, los rasgos de la personalidad, la agresion explicita y el nivel de impulsividad en pacientes con antecedentes de intentos suicidas y de sus familiares de 1er grado, se incluyeron pacientes que acudieron al Servicio de Consulta Externa, preconsulta y hospitalizacion del INPRF con antecedentes de intentos suicidas y que ademas contaron en eje I con el diagnostico psiquiatrico de algun trastorno afectivo sin comorbilidad, encontrando una asociacion entre las alteraciones del sistema serotoninergico, los rasgos de personalidad, la agresividad y el nivel de impulsividad, con la manifestacion de comportamientos suicidas, debera aclararse el significado de dicha asociacion. Palabras clave: Suicidio, agresividad, sistema serotoninergico.
Gene, 2021
BACKGROUND Neurocognitive disorders (NCDs) are characterized by cognitive decline. Most genetic s... more BACKGROUND Neurocognitive disorders (NCDs) are characterized by cognitive decline. Most genetic studies of NCDs have been focused on single-nucleotide polymorphism; other genetic variations, such as copy number variants (CNV), have been less explored. The aim of the present study was to explore CNVs associated with NCDs in a small sample of Mexican individuals and search for the frequency in a larger replication sample of individuals at high risk for or diagnosed with NCDs. METHOD The exploratory analysis analyzed whole-genome CNVs associated with NCDs in 1335 individuals, of whom 35 were diagnosed with NCDs and 1300 were population-based controls. Whole-genome CNVs were derived from PsychArray and the PennCNV algorithm. The frequency of associated CNVs in a sample of 277 individuals diagnosed with NCDs and 70 high-risk individuals was then determined using RT-PCR. RESULTS The exploratory analysis identified one deletion associated with NCDs (p = 0.007) affecting the gene MGAT4C (Mannosyl (Alpha-1,3-)-Glycoprotein Beta-1,4-N-Acetylglucosaminyltransferase, Isozyme C). In the replication sample, a frequency of 3.97% was found in individuals diagnosed with NCDs and 1.43% in high-risk individuals. CONCLUSIONS An association between a rare CNV on MGAT4C and cognitive impairment was found in this sample of the Mexican population. Nevertheless, studies with larger sample sizes are needed in order to further explore the association.
Frontiers in Pharmacology, 2020
the lowest allele frequency of Group 1. The reduction in these alleles reduces the risk of toxici... more the lowest allele frequency of Group 1. The reduction in these alleles reduces the risk of toxicity from anticancer and antihypercholesterolemic drugs. Our analysis identified different admixture patterns and described how they could be used to refine the practice of pharmacogenetic counseling for this admixed population.
Molecular Psychiatry, 2017
Two obsessive-compulsive disorder (OCD) genome-wide association studies (GWASs) have been publish... more Two obsessive-compulsive disorder (OCD) genome-wide association studies (GWASs) have been published by independent OCD consortia, the International Obsessive-Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and the OCD Collaborative Genetics Association Study (OCGAS), but many of the top-ranked signals were supported in only one study. We therefore conducted a meta-analysis from the two consortia, investigating a total of 2688 individuals of European ancestry with OCD and 7037 genomically matched controls. No single-nucleotide polymorphisms (SNPs) reached genome-wide significance. However, in comparison with the two individual GWASs, the distribution of P-values shifted toward significance. The top haplotypic blocks were tagged with rs4733767 (
European Neuropsychopharmacology, 2017
Background The efficacy of antipsychotics treatment in schizophrenia patients has long been estab... more Background The efficacy of antipsychotics treatment in schizophrenia patients has long been established; however, clinical response to these drugs is not the same in all patients. Genetic variability has been proposed as the main reason for the different outcomes.The dopaminergic pathways, the principal mechanism of action of the antipsychotics, have been the main focus of pharmacogenetic studies in schizophrenia. Some functional single nucleotide polymorphisms (SNPs) have been associated with dopamine disposition or dopamine receptor expression, modifying the response to treatment. The aim of the study was to analyze the association between two response phenotypes (patients with response and resistant) and COMT (Val58Met), DRD2 (A-241G, C/G exon 8, C939T, Taq1A) and DRD3 (Ser9Gly) gene polymorphisms. Methods Treatment response was retrospectively/prospectively assessed. First, we gathered all reliable antipsychotics assays from medical files and through interviews with attending physicians. If these data were not conclusive, a mandatory follow-up period was added with regularly scheduled ratings (using the Positive and Negative Symptom Scale PANSS and the Functional Assessment Scale for Comprehensive Treatment of Schizophrenia FACT-Sz).Treatment response was defined on a ≥ 30% decrease on the total PANSS score (with an antipsychotic different from clozapine). The sample was classified in two main phenotypes: 95 patients on response to treatment group and 81 on resistant-to-treatment group. The genotyping of the COMT (Val58Met), DRD2 (A-241G, C/G exon 8, C939T, Taq1A), and DRD3 (Ser9Gly) gene polymorphisms was performed with allelic discrimination, using TaqMan assays. Differences in genotypes and allele frequencies between the phenotypes of patients were calculated using the X2 test. Also, we performed a logistic regression analysis to predict the likelihood of the resistance-to-treatment phenotype. Results Analysis of Val158Met/COMT showed differences between the response and the resistance groups. The GG genotype (Val/Val) was more frequent in the response group than the resistance group (47% vs. 33%, X2=6.26, 2 df , p=0.04). We also found allele differences between groups (X2=6.65, 1 df, p<0.01). The Val allele was more frequent in the response group (65%) than the resistance. There were no significant associations of DRD2 (A-241G, C/G exon 8, C939T, Taq1A) or the DRD3 (Ser9Gly) SNPs with any of the phenotypes. The logistic regression model showed that the COMT/Val158Met (Met/Met) and DRD3 Ser9Gly (CT) genotypes were predictive for the resistant-to-treatment phenotype, classifying correctly 66% of them (β Exp=1.99, 1.086-3.66 CI 95%, p=0.02). Discussion The COMT/Val158Met SNP (Val/Val) was associated with the response to treatment phenotype. This finding is consistent with the antipsychotics proposed mechanism of action. The antipsychotic efficay on lowering the hyperdopaminergic state would be greater in those patients with the high-activity COMT genotype. The DRD2 SNPs analysis, the main target of several studies, did not show any significant association with the phenotypes. The COMT and DRD3 gene analyses
Salud mental, 2016
Resumen Introducción. La obesidad es la acumulación excesiva de grasa corporal, lo que condiciona... more Resumen Introducción. La obesidad es la acumulación excesiva de grasa corporal, lo que condiciona una alta comorbilidad. El consumo descontrolado de alimentos hipercalóricos es causa de su desarrollo; ésta es una conducta de características similares a la de pacientes con adicción a sustancias. La escala de adicción a los alimentos, YFAS (Yale Food Addiction Scale), permite identificar a sujetos con conducta adictiva a los alimentos. Objetivo. Validar la escala YFAS en español en una muestra de población mexicana adulta. Método. La muestra de participantes (160) respondió a la encuesta en dos ocasiones, con un período de tres semanas entre cada aplicación. La pertinencia de un modelo factorial se corroboró con las pruebas de esfericidad de Bartlett y la medición del parámetro de Kaiser-Meyer-Olkin. Resultados. El α de Cronbach = 0.7963 corroboró la consistencia interna de la escala. Para la confiabilidad se obtuvo el coeficiente de Spearman por la metodología test-retest, de r = 0.5...
Journal of the American Academy of Child & Adolescent Psychiatry, 2016
The inclusion of disruptive mood dysregulation disorder (DMDD) in the DSM-5 has generated a chang... more The inclusion of disruptive mood dysregulation disorder (DMDD) in the DSM-5 has generated a change in the paradigm of the study of chronic irritability in particular in relation to the ODD. Working groups of the ICD-11 have associated chronic irritability with dimension (or subtype) of ODD. The construct of ODD has been described with the presence of two factors with different projections to the future: the factor "irritable" and the factor "headstrong". The aim of the research was to determine the possible association between attachment styles and gene polymorphisms of the serotonin transporter with factors of ODD. Methods: The sample consists in 100 adolescent patients of the National Institute of Psychiatry in Mexico City. Patients who met criteria for ODD were invited. The parent answered the affective reactivity index (IRA) version for parents to measure chronic irritability and the Composite International Diagnostic Interview (CIDI) for ODD symptoms. The patient answered the experience in close relationship Rating Scale (ECR-RS) to measure "avoidance" and "anxiety" in relationships with parents and best friend, IRA version for subject and the CIDI. The best clinical estimate was determined for IRA and CIDI. It was taken a sample of buccal cell for genotyping the gene HTTLPR-5, which it was performed by real-time PCR. Results: 56 percent was female, mean age 15.27, 65 percent showed mixed symptoms of ODD, 24 percent showed "headstrong" symptoms and 11 percent showed "irritable" symptoms. 27 percent of the sample showed secure attachment style, 40 percent were preoccupied, 18 percent avoidant and 15 percent fearful attachment. 34 percent of the sample presents the genotypic variation (SS), 48 percent was (SL) and 14 percent (LL). No significant differences were found between subtypes of ODD and allelic gene frequencies or with attachment styles. Association was found between fearful attachment (x2¼7.8; p ¼ 0.05); heterozygote SL (x2 ¼ 06.0; p ¼ 0.03); mixed symptomatic dominance ODD (p ¼ 0.001); and comorbid diagnoses of PTSD (p ¼ 0.02) in patients with highest score of chronic irritability. Conclusions: Patients with ODD have a higher proportion of insecure attachment styles when compared to the general population. Patients with fearful attachment style were those with higher irritability while they were in the "irritable" and "mixed" category of ODD. A high prevalence of polymorphism S in the sample of patients with ODD was found.
Salud Mental, 2014
Suicide is a common cause of death in adolescents, being mainly associated with depression. In ad... more Suicide is a common cause of death in adolescents, being mainly associated with depression. In addition, the "SS" genotype and the "S" allele of 5-HTTLPR polymorphism of SLC6A4 gene of serotonin transporter have been associated with suicidal behavior. The aims of the present study were to compare the frequency of the polymorphism of SLC6A4 gene in depressed adolescents with and without history of suicidal attempt and to determine if the "SS" genotype was associated with specific clinical features. Method The study examined 53 adolescents who were evaluated with the Diagnostic Interview Schedule for Affective Disorders and Schizophrenia for school-aged children-present and lifetime version (K-SADS-PL). A DNA sample was obtained and 5HTTLPR polymorphisms of SLC6A4 gene were analyzed. Results There were no differences in the frequency of genotype and allele frequencies between groups. However, patients with the "SS" genotype reported a higher frequency of hopelessness and a greater number of suicide attempts. Conclusions The frequency of "SS" genotype did not differ between patients with and without suicidal behavior, but patients with this genotype exhibited differences in clinical features of depression which need further study.
RESUMEN Los estudios de asociación alélica en esquizofrenia se han enfocado en diversas regiones ... more RESUMEN Los estudios de asociación alélica en esquizofrenia se han enfocado en diversas regiones cromosómicas, las cuales contienen genes que codifican para receptores dopaminérgicos. Dentro de éstas, los polimorfismos del gen del receptor de dopamina D4 (DRD4) han sido ampliamente relacionados con la sintomatología psiquiátrica. Existen algunos reportes de asociaciones entre el polimorfismo 48-bp-VNTR en el exón III y la esquizofrenia, aunque esta relación aún es controvertida. La mayoría de los estudios han utilizado pacientes compara-dos contra controles o familias tipo tríos. Sin embargo, no se han presentado estudios con este polimorfismo usando familias con varios afectados. En este estudio se analizó este polimorfismo VNTR del exón III del DRD4 en 60 familias con al menos un par de hermanos afectados. Los datos se analizaron con el programa SIBPAL (software S.A.G.E). La estimación promedio de alelos compartidos fue de 0.54 (p=0.014) y la proporción estimada de parejas de herm...
Molecular psychiatry, 1996
We performed an association analysis of the DRD2, DRD3 and 5HT2A genes polymorphisms in 67 Obsess... more We performed an association analysis of the DRD2, DRD3 and 5HT2A genes polymorphisms in 67 Obsessive-Compulsive Disorder (OCD) patients and 54 healthy controls. There were no statistically significant differences in genotype or allele frequencies for any of the polymorphisms studied between OCD subjects and controls. For the subgrouped analysis, no results were significant after correction for multiple testing, although homozygosity of DRD2/A2A2 in subjects displaying vocal or motor tics approached significance compared to controls (Fisher exact test, P = 0.008). Our results may follow the notion that OCD patients with tics represent a different genetic subtype of the disease.
Revista de investigación clínica; organo del Hospital de Enfermedades de la Nutrición
This investigation reports an association study with alleles of the dopaminergic system genes (ty... more This investigation reports an association study with alleles of the dopaminergic system genes (tyrosine hydroxylase (TH), D2 and D4 receptors) in schizophrenic patients and non-schizophrenic subjects. The genotypes were typed using a polymerase chain reactions PCR-based CA repeat polymorphisms. There were no significant associations between the studied alleles and schizophrenia. Also, a linkage analysis was performed using the same genes (TH, D2 and D4) in two multiple affected schizophrenic families. There was no linkage among any of three genes and schizophrenia. The maximum lod score (Z = 0.43, theta = 0.10 penetrance 100%) was for the tyrosine hydroxylase gene. Linkage analysis significantly excluded the D2 receptor gene (Z = 5.6, theta = 0.01), assuming an autosomal dominant pattern and complete penetrance, However, when the lod scores were calculated with other penetrance values, they lost significance.
Actas españolas de psiquiatría
The aim of the present study was to assess the association between the serotonin transporter gene... more The aim of the present study was to assess the association between the serotonin transporter gene and the Temperament and Character Inventory (TCI) personality dimensions in subjects without psychopathology. Fifty seven individuals without psychiatric symptoms were assessed with the SCL-90, and the TCI. In all subjects a peripheral blood sample was taken to determine their genotypes, after informed consent. Three groups were formed according to the 5-HTT genotype: SS, SL and LL, and the TCI results were compared. There was no association among the 5-HTT genotypes and any of the TCI subscales. There were also no statistical differences among any of the three groups divided by genotype only according to the TCI scores, as well as when compared with historical controls. These results are consistent with other studies that have not found associations among the different measurements of personality and 5-HTT genotypes. Likewise, our data suggest that our sample can be useful as a source ...
Salud Mental, 1998
Resumen En este trabajo se reportan los resultados de un estudio paralelo al proyecto de eficacia... more Resumen En este trabajo se reportan los resultados de un estudio paralelo al proyecto de eficacia y seguridad de la f luvoxamina vs imipramina en el tratamiento de la depresión mayor, El estudio fue doble ciego, controlado y multicéntrico, y se ana-
Molecular Psychiatry, 2013
European Neuropsychopharmacology, 2013
Obsessive-compulsive disorder (OCD) is a psychiatric disorder whose etiology is not yet known. We... more Obsessive-compulsive disorder (OCD) is a psychiatric disorder whose etiology is not yet known. We investigate the role of three variants of the BDNF gene (rs6265, rs1519480 and rs7124442) by single SNP and haplotype analysis in OCD Mexican patients using a case-control and family-based association design. BDNF gene variants were genotyped in 283 control subjects, 232 OCD patients and first degree relatives of 111 OCD subjects. Single SNP analysis in case-control study showed an association between rs6265 and OCD with a high frequency of Val/Val genotype and Val allele (p=0.0001 and p=0.0001, respectively). Also, genotype and allele analysis of rs1519480 showed significant differences (p=0.0001, p=0.0001; respectively) between OCD and control groups. Haplotype analysis showed a high frequency of A-T (rs6265-rs1519480) in OCD patients compared with the control group (OR=2.06 [1.18-3.59], p=0.0093) and a low frequency of haplotype A-C in the OCD patients (OR=0.04 [0.01-0.16], p=0.000002). The family-based association study showed no significant differences in the transmission of any variant. Our study replicated the association between BDNF Val66Met gene polymorphism and OCD. Also, we found a significant association of rs1519480 in OCD patients compared with a control group, region that has never been analyzed in OCD. In conclusion, our findings suggest that BDNF gene could be related to the development of OCD.