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Schizophrenia (SCZ) and bipolar disorder (BD) cause similar symptomatology. A correlation between these disorders has been found. We aimed to explore shared CNVs between SCZ and BD, in 35 sibpairs diagnosed with SCZ and 21 sibpairs diagnosed with BD. CNV calling was performed using data derived of Psycharray, by PennCNV. We did not find any shared CNVs between individuals diagnosed with BD and SCZ, neither with psychotic symptoms in individuals with BD. Nevertheless, we found a significant higher CNV burden in early-onset SCZ. This is one of the first's studies analyzing shared CNVs between SCZ and BD in Mexican population.
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Trastorno Bipolar/genética , Variaciones en el Número de Copia de ADN/genética , Predisposición Genética a la Enfermedad/genética , Esquizofrenia/genética , Hermanos , Adulto , Trastorno Bipolar/epidemiología , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Esquizofrenia/epidemiologíaRESUMEN
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.
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Metilación de ADN , Herencia Multifactorial , Ideación Suicida , Intento de Suicidio , Epigénesis Genética , HumanosRESUMEN
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.
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Trastorno Bipolar/epidemiología , Trastornos Mentales/epidemiología , Esquizofrenia/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Adulto , Trastorno Bipolar/genética , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/genética , Diagnóstico Dual (Psiquiatría) , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Trastornos Mentales/genética , México , Persona de Mediana Edad , Esquizofrenia/genética , Trastornos Relacionados con Sustancias/genética , Adulto JovenRESUMEN
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.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adulto Joven , Esquizofrenia/epidemiología , Trastorno Bipolar/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Mentales/epidemiología , Esquizofrenia/genética , Trastorno Bipolar/genética , Diagnóstico Dual (Psiquiatría) , Trastornos Relacionados con Sustancias/genética , Predisposición Genética a la Enfermedad , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/epidemiología , Estudio de Asociación del Genoma Completo , Trastornos Mentales/genética , MéxicoRESUMEN
INTRODUCTION: Several studies indicate that polygenic obesity is linked to fat-mass and obesity-associated (FTO) genetic variants. Nevertheless, the link between variants in FTO and mental disorders has been barely explored. The present work aims to determine whether FTO genetic variants are associated with bipolar disorder and obesity, and to perform an in silico prediction of variant-dependent functional impact on the developing brain transcriptome. METHODS: Four hundred and forty-six Mexican mestizos were included in a genetic association analysis. SNP-sequence kernel association test and linear mixed models were implemented for genetic association assessment. For functional impact prediction, we analyzed the mapping of regulatory elements, the modification of binding sites of transcription factors and the expression of transcription factors in the brain developing transcriptome, searching on different databases. RESULTS: In the set-based analysis, we found different associated regions to BD (bipolar disorder) and obesity. The promoter flanking region of FTO intron 1 was associated with differential effects on BMI, while intron 2 of RPGRIP1L and FTO upstream regions were associated with BD. The prediction analysis showed that FTO BD-associated variants disturb binding sites of SP1 and SP2; obesity-associated variants, on the other hand, disturb binding sites of FOXP1, which are transcription factors highly expressed during prenatal development stages of the brain. CONCLUSION: Our results suggest a possible effect of FTO variants on neurodevelopment in obesity and bipolar disorder, which gives new insights into the molecular mechanism underlying this association.
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Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Trastorno Bipolar/genética , Simulación por Computador , Predisposición Genética a la Enfermedad/genética , Obesidad/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Índice de Masa Corporal , Femenino , Humanos , Masculino , MéxicoRESUMEN
We previously identified bipolar disorder (BD) susceptibility loci on 8q24, 14q32, and 2q12-14 in a genome-wide nonparametric linkage screen in a Latino cohort. We now perform a fine mapping analysis using a dense map of additional SNPs to identify BD susceptibility genes within these regions. One thousand nine hundred and thirty-eight individuals with Latino ancestry (880 individuals with BD Type I or Schizoaffective, Bipolar Type) from 416 Latino pedigrees from the United States, Mexico, Costa Rica, and Guatemala were genotyped with 3,074 SNPs to provide dense coverage of the 8q24 (11.5 cM), 14q32 (7.5 cM), and 2q12-14 (6.5 cM) chromosomal loci. Single-marker association tests in the presence of linkage were performed using the LAMP software. The top linkage peak (rs7834818; LOD = 5.08, p = 3.30E - 5) and associated single marker (rs2280915, p = 2.70E - 12) were located within FBXO32 on 8q24. On chromosome 2, the top linkage peak (rs6750326; LOD = 5.06, p = 3.50E - 5) and associated single marker (rs11887088, p = 2.90E - 6) were located in intragenic regions near ACTR3 and DPP10. None of the additional markers in the region around chromosome 14q32 met significance levels for linkage or association. We identified six SNPs on 2q12-q14 and one SNP in FBXO32 on 8q24 that were significantly associated with BD in this Latino cohort.
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Trastorno Bipolar/genética , Cromosomas Humanos Par 2/genética , Trastornos Psicóticos/genética , Proteína 3 Relacionada con la Actina/genética , Proteína 3 Relacionada con la Actina/metabolismo , Adulto , Trastorno Bipolar/psicología , Mapeo Cromosómico/métodos , Costa Rica , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/genética , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/metabolismo , Femenino , Ligamiento Genético/genética , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Guatemala , Hispánicos o Latinos/genética , Humanos , Escala de Lod , Masculino , México , Persona de Mediana Edad , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Polimorfismo de Nucleótido Simple/genética , Trastornos Psicóticos/psicología , Proteínas Ligasas SKP Cullina F-box/genética , Proteínas Ligasas SKP Cullina F-box/metabolismo , Estados UnidosRESUMEN
OBJECTIVES: Recent genome-wide association studies (GWASs) have identified numerous putative genetic polymorphisms associated with bipolar disorder (BD) and/or schizophrenia (SC). We hypothesized that a portion of these polymorphisms would also be associated with BD in the Latino American population. To identify such regions, we tested previously identified genetic variants associated with BD and/or SC and ancestral haploblocks containing these single nucleotide polymorphisms (SNPs) in a sample of Latino subjects with BD. METHODS: A total of 2254 Latino individuals were genotyped for 91 SNPs identified in previous BD and/or SC GWASs, along with selected SNPs in strong linkage disequilibrium with these markers. Family-based single marker and haplotype association testing was performed using the PBAT software package. Empirical P-values were derived from 10 000 permutations. RESULTS: Associations of eight a priori GWAS SNPs with BD were replicated with nominal (P≤.05) levels of significance. These included SNPs within nuclear factor I A (NFIA), serologically defined colon cancer antigen 8 (SDCCAG8), lysosomal associated membrane protein 3 (LAMP3), nuclear factor kappa B subunit 1 (NFKB1), major histocompatibility complex, class I, B (HLA-B) and 5'-nucleotidase, cytosolic II (NT5C2) and SNPs within intragenic regions microRNA 6828 (MIR6828)-solute carrier family 7 member 14 (SLC7A14) and sonic hedgehog (SHH)-long intergenic non-protein coding RNA 1006 (LINC01006). Of the 76 ancestral haploblocks that were tested for associations with BD, our top associated haploblock was located in LAMP3; however, the association did not meet statistical thresholds of significance following Bonferroni correction. CONCLUSIONS: These results indicate that some of the gene variants found to be associated with BD or SC in other populations are also associated with BD risk in Latinos. Variants in six genes and two intragenic regions were associated with BD in our Latino sample and provide additional evidence for overlap in genetic risk between SC and BD.
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Trastorno Bipolar , Factores de Transcripción de Tipo Kruppel/genética , Proteínas de Membrana de los Lisosomas/genética , Subunidad p50 de NF-kappa B/genética , Proteínas de Neoplasias/genética , Esquizofrenia , Adulto , Trastorno Bipolar/etnología , Trastorno Bipolar/genética , Costa Rica/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Estudio de Asociación del Genoma Completo , Guatemala/epidemiología , Haplotipos , Hispánicos o Latinos/genética , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Desequilibrio de Ligamiento , Masculino , México/epidemiología , Polimorfismo de Nucleótido Simple , Esquizofrenia/etnología , Esquizofrenia/genética , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: The brain-derived neurotrophic factor (BDNF) has been considered as an important candidate gene in bipolar disorder (BD); this association has been derived from several genetic and genome-wide studies. A polymorphic variant of the BDNF (Val66Met) confers some differences in the clinical presentation of affective disorders. In this study, we evaluated a sample population from Mexico City to determine whether the BDNF (rs6265) Val66Met polymorphism is associated with the body mass index (BMI) of patients with BD. METHODS: This association study included a sample population of 357 individuals recruited in Mexico City. A total of 139 participants were diagnosed with BD and 137 were classified as psychiatrically healthy controls (all individuals were interviewed and evaluated by the Diagnostic Interview for Genetic Studies). Genomic DNA was extracted from peripheral blood leukocytes. The quantitative polymerase chain reaction (qPCR) assay was performed in 96-well plates using the TaqMan Universal Thermal Cycling Protocol. After the PCR end point was reached, fluorescence intensity was measured in a 7,500 real-time PCR system and evaluated using the SDS v2.1 software, results were analyzed with Finetti and SPSS software. Concerning BMI stratification, random groups were defined as follows: normal <25 kg/m(2), overweight (Ow) =25.1-29.9 kg/m(2), and obesity (Ob) >30 kg/m(2). RESULTS: In the present work, we report the association of a particular BMI phenotype with the presence of the Val66Met allele in patients with BD (P=0.0033 and odds ratio [95% confidence interval] =0.332 [157-0.703]), and correlated the risk for valine allele carriers with Ow and Ob in patients with BD. CONCLUSION: We found that the methionine allele confers a lower risk of developing Ow and Ob in patients with BD. We also confirmed that the G polymorphism represents a risk of developing Ow and Ob in patients with BD. In future studies, the haplotype analysis should provide additional evidence that BDNF may be associated with BD and BMI within the Mexican population.
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OBJECTIVES: Through recent genome-wide association studies (GWASs), several groups have reported significant association between variants in the calcium channel, voltage-dependent, L-type, alpha 1C subunit (CACNA1C) and bipolar disorder (BP) in European and European-American cohorts. We performed a family-based association study to determine whether CACNA1C is associated with BP in the Latino population. METHODS: This study included 913 individuals from 215 Latino pedigrees recruited from the USA, Mexico, Guatemala, and Costa Rica. The Illumina GoldenGate Genotyping Assay was used to genotype 58 single-nucleotide polymorphisms (SNPs) that spanned a 602.9-kb region encompassing the CACNA1C gene including two SNPs (rs7297582 and rs1006737) previously shown to associate with BP. Individual SNP and haplotype association analyses were performed using Family-Based Association Test (version 2.0.3) and Haploview (version 4.2) software. RESULTS: An eight-locus haplotype block that included these two markers showed significant association with BP (global marker permuted p = 0.0018) in the Latino population. For individual SNPs, this sample had insufficient power (10%) to detect associations with SNPs with minor effect (odds ratio = 1.15). CONCLUSIONS: Although we were not able to replicate findings of association between individual CACNA1C SNPs rs7297582 and rs1006737 and BP, we were able to replicate the GWAS signal reported for CACNA1C through a haplotype analysis that encompassed these previously reported significant SNPs. These results provide additional evidence that CACNA1C is associated with BP and provides the first evidence that variations in this gene might play a role in the pathogenesis of this disorder in the Latino population.
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Trastorno Bipolar/genética , Canales de Calcio/genética , Salud de la Familia , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Costa Rica , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Guatemala , Haplotipos , Hispánicos o Latinos/genética , Humanos , Masculino , México , Estados UnidosRESUMEN
We investigated the prevalence of "high" levels of depressive symptomatology and 13 health-related medical conditions in elderly Mexican American (MA) and non-Hispanic white (NHW) residents of El Paso County, Texas. We analyzed the extent to which depressive symptoms in this population are associated with these conditions. Elderly MA residents possessed a higher prevalence of current depression, a relatively unique health-related condition profile, and were more likely to experience a set of conditions that impede participation in daily life-conditions that we found to be strongly associated with high depressive symptomatology in the elderly. After adjusting for educational attainment, using multiple regression analyses, depression was not associated with ethnicity and only six of the health related conditions showed significant differences between MA and NHW subjects. We believe these results provide an important insight into the mechanism of health-related conditions and depressive symptomatology in a large sample of elderly MAs; and how conditions typically attributed to MA ethnicity may in actuality be an artifact of socioeconomic status variables such as educational-attainment.
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The population of Costa Rica has been considered valuable for locating susceptibility genes of complex disorders because of historical events and a gradual admixture process. We present an assessment of 426 unrelated individuals with a familial history of mental disorder and with ancestors born in the Central Valley, genotyped at 730 microsatellites to evaluate genetic diversity, ancestry, and substructure at the general and regional population levels using quantitative methods. Low population substructure was found. Estimated mean ancestry proportions were 54%, 32%, and 13% for European, Amerindian, and African components, respectively, with some regional variation. The F(ST) values obtained confirm the largest genetic similarity to Europeans. Subdivision of the Amerindians into individual populations revealed strong similarity to Chibchan groups. Analysis of the African ancestry showed high similarity to West and Central African populations. Gene ancestries from other African areas were also detected, probably resulting from ancestral admixture within Africa prior to colonial times. Our analyses show, in an ethnohistorical-genetic context, that gene flow and admixture are important components of Costa Rican population history. The results confirm the need to consider the particular regional genetic structure, the effects of genetic drift and the ancestry when designing and interpreting investigations of genetic traits in this population.
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Indio Americano o Nativo de Alaska/genética , Población Negra/genética , Genética de Población , Trastornos Mentales/genética , Población Blanca/genética , África , Costa Rica , Etnicidad/genética , Femenino , Flujo Génico , Frecuencia de los Genes , Variación Genética , Genotipo , Humanos , Masculino , Repeticiones de Microsatélite , Análisis de Componente Principal , ReproducciónRESUMEN
Depression and suicidal behavior are frequently observed in patients with schizophrenia. The serotonin transporter protein regulates serotonergic signaling at synapses and is encoded by a single gene (SLC6A4; Locus Link ID: 6532), located at 17q11.1-q12 with two polymorphic variants (the short and the long allele). The short allele of serotonin transporter gene has been associated with depression and suicidality in individuals who suffered negative life events and with depression in individuals with chronic psychosis.. Subjects were recruited from a genetic study of schizophrenia conducted in Costa Rica. The authors replicated their previous research, using a more narrow phenotype (only schizophrenic subjects) and a more ethnically homogenous sample (only Costa Rican schizophrenic individuals who were not included in the previous study). The authors hypothesized that subjects with at least one copy of the serotonin transporter promoter gene polymorphism (5-HTTLPR) "s" allele would have a greater history of lifetime depression and suicidability rate than those who had an "l/l" genotype. The authors analyzed 155 subjects with a DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnosis of schizophrenia (73% male, age at interview 38.3, SD = 11.23). The genotype distribution was "ss" 58 (37%), "sl" 69 (45%), and "ll" 28 (18%). In the secondary analysis, the authors explored association of the "s" allele with lifetime history of suicide behavior in 173 subjects (18 more subjects than primary analysis because schizophrenic individuals were included regardless of history of depression). The authors found that subjects carrying at least one short allele had a significant increased lifetime risk for depressive syndromes (chi(2) = 5.4, df = 1, P = 0.02; odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.15-6.3). No association was found for suicidal behavior in the same sample (chi(2) = 0.928, P = 0.629). In conclusion, the genotype at the 5-HTTLPR promoter polymorphic locus increases the risk of developing major depression but not suicidal behavior during the course of the schizophrenia in these patients. Due to the small sample size, these results should be followed by definitive replication.
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Trastorno Depresivo/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo Genético/genética , Regiones Promotoras Genéticas/genética , Esquizofrenia/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Adulto , Estudios de Cohortes , Comorbilidad , Costa Rica , Trastorno Depresivo/epidemiología , Femenino , Marcadores Genéticos/genética , Humanos , Masculino , Persona de Mediana Edad , Tamaño de la Muestra , Esquizofrenia/epidemiología , Intento de SuicidioRESUMEN
OBJECTIVES: The aims of this study were to estimate the frequency and course of substances use disorders in Latino patients with schizophrenia and to ascertain risk factors associated with substance use disorders in this population. METHOD: We studied 518 subjects with schizophrenia recruited for a genetic study from the Southwest United States, Mexico, and Central America (Costa Rica and Guatemala). Subjects were assessed using structured interviews and a best estimate consensus process. Logistic regression, chi(2), t test, Fisher's exact test, and Yates' correction, as appropriate, were performed to assess the sociodemographic variables associated with dual diagnosis. We defined substance use disorder as either alcohol or substance abuse or dependence. RESULTS: Out of 518 patients with schizophrenia, 121 (23.4%) had substance use disorders. Comorbid substance use disorders were associated with male gender, residence in the United States, immigration of Mexican men to the United States, history of depressive syndrome or episode, and being unemployed. The most frequent substance use disorder was alcohol abuse/dependence, followed by marijuana abuse/dependence, and solvent abuse/dependence. CONCLUSION: This study provides data suggesting that depressive episode or syndrome, unemployment, male gender, and immigration of Mexican men to the United States were factors associated with substance use disorder comorbidity in schizophrenia. Binary logistic regression showed that country of residence was associated with substance use disorder in schizophrenic patients. The percentage of subjects with comorbid substance use disorders was higher in the Latinos living in the United States compared with subjects living in Central America and Mexico.
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Salud de la Familia , Hispánicos o Latinos , Esquizofrenia/epidemiología , Esquizofrenia/genética , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/genética , Adulto , Edad de Inicio , Distribución de Chi-Cuadrado , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , Sudoeste de Estados Unidos/epidemiología , Trastornos Relacionados con Sustancias/clasificaciónRESUMEN
INTRODUCTION: Schizophrenia (SC) and bipolar disorder (BP) are two of the most severe and incapacitating mental disorders. It has been questioned whether these two conditions designate distinct illnesses with different etiologies or whether they represent different ends of a clinical spectrum with a common etiology. MATERIALS AND METHODS: This study compares social and clinical characteristics of 84 SC and 84 BP subjects from the Costa Rican Central Valley (CRCV) using information from the DIGS, FIGS and psychiatric records. Each of these subjects had a best estimate lifetime consensus diagnosis of either bipolar type I or SC. RESULTS: Subjects with SC differed from subjects with BP in social adjustment measures like marital and employment status, and number of children. Both groups were very similar in years of education, age of onset of their illness, history of other psychiatric co-morbidities, and treatment received. DISCUSSION: The high percentage of psychosis in the BP group (97.6%) may largely explain the similarities found between groups in their clinical characteristics. CONCLUSION: The differences in social and functional decline support the original dichotomy described by Kraepelin based on chronicity and periodicity between these two psychotic disorders.
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Trastorno Bipolar/diagnóstico , Esquizofrenia/diagnóstico , Adulto , Edad de Inicio , Trastorno Bipolar/epidemiología , Trastorno Bipolar/genética , Comorbilidad , Costa Rica/epidemiología , Diagnóstico Diferencial , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Escolaridad , Empleo , Femenino , Humanos , Masculino , Estado Civil , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/genética , Esquizofrenia/epidemiología , Esquizofrenia/genética , Ajuste SocialRESUMEN
BACKGROUND: Although genetic influences on bipolar I disorder are well established, localization of genes that predispose to the illness has been difficult. Some genes predisposing to bipolar I disorder may be transmitted without expression of the categorical clinical phenotype. One strategy to overcome this obstacle is the use of quantitative endophenotypes, as has been done for other medical disorders. METHODS: We analyzed 30 bipolar I extended families (300 subjects, average family size 10.34 members, range: 2-31) and 20 unrelated healthy controls from a Costa Rican sample. Heritability and genetic correlation of the state and trait scale from the Anxiety State and Trait Inventory was computed by using the general linear model (SOLAR package software). We also assessed variation of both scores among groups (patients, relatives and controls) and tested independence of affection status. RESULTS: Heritability for state is 0.45 (SE=0.11, p=0.0000001) and for trait is 0.89 (SE=0.06, p=6.22e-29). Genetic correlation for state and trait is 0.29, (SE=0.12, p=0.038-3.19e-8). Bipolar I patients showed the highest trait score (F=12.17 [5,24], p=0.002), (bipolar I patients>relatives with other pathologies, >healthy relatives>unrelated healthy controls) with normal distribution in healthy individuals and no difference regarding depression and mania current status, (F=0.230, df=1, p=0.632 and F=1.401, df=1, p=0.238, respectively), contrary to the state score. LIMITATIONS: Confounding factors such as comorbid disorders could affect the interaction of subclinical anxiety with mania. Due to our limited budget we were not able to re-evaluate the subjects and conduct a test retest to assess the STAI reliability and mood state independence of anxiety traits over different times. Further research is needed to evaluate if anxiety traits are specially related to bipolar I disorder in comparison with other traits such as anger, attention or response inhibition deficit, pathological impulsivity or low self-directedness. CONCLUSIONS: Anxiety state and trait are heritable and share some genetic factors but only trait showed normal distribution in healthy subjects, mood current status independence and significant liability for bipolar I disorder. A stair-step distribution of trait anxiety scores in the family members and controls based on their genetic proximity to affected individuals and diagnostic status suggests that trait anxiety could be an endophenotype in these bipolar I families.
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Afecto , Ansiedad/psicología , Trastorno Bipolar/psicología , Familia/psicología , Pacientes/psicología , Adulto , Factores de Edad , Ansiedad/epidemiología , Ansiedad/genética , Trastorno Bipolar/epidemiología , Trastorno Bipolar/genética , Costa Rica/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Linaje , Determinación de la Personalidad , Fenotipo , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
To investigate the role of the apolipoprotein E (APOE) gene in schizophrenia, the authors analyzed 60 families with this mental disorder. An association in the presence of linkage test (APL) and haplotypes analysis were undertaken using the APL v1.1 software. A global allelic transmitted was significant for APOE-epsilon3 (chi(2)=6.24, p=0.01); this allele is mainly carried by female patients (chi(2)=8.33, p=0.003), whereas APOE-219G is preferentially transmitted in males (p=0.02). Furthermore, our results show that haplotypes APOE-epsilon3/APOE-219G are associated with schizophrenia (chi(2)=11.61, p=0.01). These results provide evidence that the APOE gene may play a significant role in the etiology of schizophrenia in the Mexican population.
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Apolipoproteínas E/genética , Predisposición Genética a la Enfermedad/genética , Haplotipos/genética , Esquizofrenia/genética , Alelos , Distribución de Chi-Cuadrado , Femenino , Ligamiento Genético/genética , Genotipo , Humanos , Masculino , México , Selección de Paciente , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , HermanosRESUMEN
We determined the rates of agreement between diagnoses, using the Diagnostic Interview for Genetic Studies (DIGS) and diagnoses arrived at, using additional sources of information, to establish whether there are differences in agreement between direct interview diagnoses at US and non-US sites in comparison best estimate consensus process and to identify diagnoses that could increase diagnostic error when only the DIGS is used. DIGS diagnoses were compared with consensus diagnoses that used the same DIGS interview, plus Family Interview for Genetic Studies (FIGS) and review of medical records in 342 psychotic subjects. We found similar numbers of subjects diagnosed with schizophrenia (225 by direct interview, and 232 by consensus process). The majority of those "misdiagnosed" by direct interview had mood disorder by the consensus. Over 10% of the total subjects diagnosed by direct interview as not meeting criteria for schizophrenia had schizophrenia by consensus. There were no statistically significant differences between countries (US vs. non-US sites) in the agreement rate between direct interview diagnosis and consensus diagnosis. In conclusion, a final best-estimate process is essential to make diagnostic distinctions and to reduce diagnostic misclassifications for both research studies and in clinical practice.
Asunto(s)
Consenso , Hispánicos o Latinos/psicología , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Esquizofrenia/diagnóstico , Adulto , América Central , Comparación Transcultural , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Familia , Femenino , Humanos , Masculino , Registros Médicos , México , Trastornos del Humor/diagnóstico , Psicometría , Trastornos Psicóticos/clasificación , Trastornos Psicóticos/diagnóstico , Esquizofrenia/clasificación , Psicología del Esquizofrénico , Encuestas y Cuestionarios , Estados UnidosRESUMEN
OBJECTIVE: The present study investigated a new set of families of Latin American ancestry in order to detect the location of genes predisposing to schizophrenia and related psychotic disorders. METHOD: A genome-wide scan was performed for 175 newly recruited families with at least two siblings suffering from a psychotic disorder. Best-estimate consensus procedures were used to arrive at diagnoses, and nonparametric allele-sharing statistics were calculated to detect linkage. RESULTS: Genome-wide significant evidence for linkage for the phenotype of DSM-IV schizophrenia or schizoaffective disorder was found in a region on chromosome 17q21 (lod score, 3.33). A region on chromosome 15q22-23 showed suggestive evidence of linkage with this same phenotype (lod score, 2.11). Analyses using a broader model (any psychosis) yielded evidence of suggestive linkage for the 17q21 region only, and no region achieved genome-wide significance of linkage. CONCLUSIONS: The new set of 175 families of Mexican and Central American ancestry delineates two new loci likely to harbor predisposition genes for schizophrenia and schizoaffective disorder. The region with the strongest support for linkage in this sample, 17q21, has been implicated in meta-analyses of schizophrenia genome screens, but the authors found no previous reports of it as a locus for schizophrenia in specific population- or family-based studies, and it may represent the location of a schizophrenia predisposition gene (or genes) of special relevance in Mexican and Central American populations.
Asunto(s)
Mapeo Cromosómico , Cromosomas Humanos Par 17/genética , Hispánicos o Latinos/genética , Americanos Mexicanos/genética , Trastornos Psicóticos/genética , Esquizofrenia/genética , Ligamiento Genético/genética , Predisposición Genética a la Enfermedad/genética , Genotipo , Hispánicos o Latinos/psicología , Humanos , Escala de Lod , Americanos Mexicanos/psicología , Fenotipo , Trastornos Psicóticos/etnología , Esquizofrenia/etnología , Sudoeste de Estados UnidosRESUMEN
This study attempted to replicate evidence for association of the Epsin 4 gene (which encodes enthoprotin, a protein involved in vesicular transport) to schizophrenia in a new sample of families segregating schizophrenia drawn from the Latin American population. 1,423 subjects (767 with a history of psychosis) from 337 Latino families were genotyped using three single nucleotide polymorphisms (SNPs) spanning the Epsin 4 gene. A family based association test was utilized to test for association of these SNPs to the phenotypes of psychosis and schizophrenia. Haplotypes defined by these three SNPs showed significant association to the phenotype of psychosis in this sample (global p value=0.014, bi-allelic p value=0.047). Variation in the Epsin 4 gene is significantly associated with psychotic disorder in this Latino population. This provides additional support for the involvement of enthoprotin in the pathogenesis of schizophrenia and other psychotic disorders.