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The relationship between the gut-brain-microbiome axis has gained great importance in the study of psychiatric disorders, as it may represent a new target for their treatment. To date, the available literature suggests that the microbiota may influence the pathophysiology of several diseases, including psychosis. The aim of this review is to summarize the clinical and preclinical studies that have evaluated the differences in microbiota as well as the metabolic consequences related to psychosis. Current data suggest that the genera Lactobacillus and Megasphaera are increased in schizophrenia (SZ), as well as alterations in the glutamate-glutamine-GABA cycle, serum levels of tryptophan, kynurenic acid (KYNA), and short-chain fatty acids (SCFAs). There are still very few studies on early-onset psychosis, thus more studies are needed to be able to propose targeted therapies for a point when the disease has just started or has not yet progressed.
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INTRODUCTION: Obsessive-compulsive disorder (OCD) is characterized by a range of phenotypic expressions. Gender may be a relevant factor in mediating the disorder's heterogeneity. The aim of the present report was to explore a large multisite clinical sample of OCD patients, hypothesizing existing demographic, geographical and clinical differences between male and female patients with OCD. METHODS: Socio-demographic and clinical variables of 491 adult OCD outpatients recruited in the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network were investigated with a retrospective analysis on a previously gathered set of data from eleven countries worldwide. Patients were assessed through structured clinical interviews, the Yale- Brown Obsessive-Compulsive Scale (Y-BOCS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Self-rating Depression Scale (SDS). RESULTS: Among females, adult onset (>18 years old) was significantly over-represented (67% vs. 33%, p < 0.005), and females showed a significantly older age at illness onset compared with males (20.85 ± 10.76 vs. 17.71 ± 8.96 years, p < 0.005). Females also had a significantly lower education level than males (13.09 ± 4.02 vs. 13.98 ± 3.85 years; p < 0.05), a significantly higher rate of being married (50.8% vs. 33.5%; p < 0.001) and a higher rate of living with a partner (47.5% vs. 37.6%; p < 0.001) than males. Nonetheless, no significant gender differences emerged in terms of the severity of OCD symptoms nor in the severity of comorbid depressive symptoms. No predictive effect of gender was found for Y-BOCS, MADRS and SDS severity. DISCUSSION/CONCLUSIONS: Our findings showed significant differences between genders in OCD. A sexually dimorphic pattern of genetic susceptibility may have a crucial role to OCD clinical heterogeneity, potentially requiring different specific therapeutic strategies. Further research is warranted to validate gender as an important determinant of the heterogeneity in OCD.
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Transtorno da Personalidade Compulsiva , Transtorno Obsessivo-Compulsivo , Adolescente , Adulto , Comorbidade , Escolaridade , Feminino , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno Obsessivo-Compulsivo/terapia , Estudos RetrospectivosRESUMO
Objective: Individuals with schizophrenia and substance use disorders have a poor prognosis and increased psychiatric symptoms. The present study aimed to explore the association of 106 genes in individuals with schizophrenia and comorbid substance use through a next-generation sequencing (NGS) analysis and different in silico algorithms. Methods: We included 105 individuals diagnosed with schizophrenia and a family history of schizophrenia, of whom 49 (46.67%) presented comorbid substance use. Using NGS, we sequenced 106 genes previously associated with schizophrenia. Logistic regression models were used to assess differences in allele frequencies, and a generalized gene-set analysis was performed at the gene level. Functional annotations were performed using different algorithms and databases. Results: We identified a total of 3,109 variants, of which 25 were associated with schizophrenia and comorbid substance use and were located in regulatory and coding regions. We found low-frequency variants in COMT p.Ala72Ser, independently of p.Val158Met, that were associated with substance use. The endocannabinoid functional variant FAAH p.Pro129Thr was also associated with substance use. Conclusions: Genetic variants of genes related to dopaminergic and cannabinoid neurotransmitter systems were associated with comorbid substance use in schizophrenia. Nevertheless, more studies with larger sample sizes are needed to confirm our findings.
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OBJECTIVE: Individuals with schizophrenia and substance use disorders have a poor prognosis and increased psychiatric symptoms. The present study aimed to explore the association of 106 genes in individuals with schizophrenia and comorbid substance use through a next-generation sequencing (NGS) analysis and different in silico algorithms. METHODS: We included 105 individuals diagnosed with schizophrenia and a family history of schizophrenia, of whom 49 (46.67%) presented comorbid substance use. Using NGS, we sequenced 106 genes previously associated with schizophrenia. Logistic regression models were used to assess differences in allele frequencies, and a generalized gene-set analysis was performed at the gene level. Functional annotations were performed using different algorithms and databases. RESULTS: We identified a total of 3,109 variants, of which 25 were associated with schizophrenia and comorbid substance use and were located in regulatory and coding regions. We found low-frequency variants in COMT p.Ala72Ser, independently of p.Val158Met, that were associated with substance use. The endocannabinoid functional variant FAAH p.Pro129Thr was also associated with substance use. CONCLUSIONS: Genetic variants of genes related to dopaminergic and cannabinoid neurotransmitter systems were associated with comorbid substance use in schizophrenia. Nevertheless, more studies with larger sample sizes are needed to confirm our findings.
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Amidoidrolases , Catecol O-Metiltransferase , Esquizofrenia , Transtornos Relacionados ao Uso de Substâncias , Amidoidrolases/genética , Catecol O-Metiltransferase/genética , Frequência do Gene/genética , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Esquizofrenia/epidemiologia , Esquizofrenia/genética , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/genética , Transtornos Relacionados ao Uso de Substâncias/psicologiaRESUMO
BACKGROUND: The acceleration of the epigenetic clock has been associated with a reduction in life expectancy. Individuals diagnosed with a psychiatric disorder have a reduction in life expectancy, and some studies have correlated it with accelerated aging. OBJECTIVE: The present study aims to explore whether the presence of any psychiatric disorder could accelerate the epigenetic clock in monozygotic twins. METHODS: A total of 15 pairs of monozygotic twins were included. Epigenetic age in peripheral blood cells was estimated by previously published algorithms, using the 450K Beadchip microarray. RESULTS: We found that in twins with a diagnosis of a psychiatric disorder, the epigenetic clock could increase compared to their twin without a psychiatric disorder. DISCUSSION AND CONCLUSION: The presence of some psychiatric disorder could accelerate the epigenetic clock in homozygous twins, but studies with larger samples are required to clarify this relationship.
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Transtornos Mentais , Gêmeos Monozigóticos , Envelhecimento , Metilação de DNA , Epigênese Genética , Humanos , Transtornos Mentais/diagnóstico , Transtornos Mentais/genéticaRESUMO
INTRODUCTION: Obsessive-compulsive disorder (OCD), characterized by repetitive anxiety-inducing intrusive thoughts and compulsive behaviors, is associated with higher suicide ideation and suicide attempts than the general population. This study investigates the prevalence and the correlates of current suicide risk in adult outpatients in an international multisite cross-sectional sample of OCD outpatients. METHODS: Data were derived from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network's cross-sectional data set (N = 409). Current suicide risk (assessed by Item C of the MINI) and diagnoses of psychiatric disorders were based on DSM-IV. Chi-squared test for categorical variables and t-test for continuous variables were used to make statistical inferences about main features associated with current suicide risk. P < .05 was considered as statistically significant. RESULTS: The prevalence of current suicidal risk was 15.9%, with equal likelihood in sociodemographic variables, including age and gender. Increased rates of major depression and generalized anxiety disorder were associated to higher current suicide risk. Current suicide risk was also associated with higher severity of OCD, depressive comorbidity, and higher levels of disability. There were no significant differences in treatment correlates-including type of treatment and psychiatric hospitalizations-between the groups of individuals with and without current suicide risk. CONCLUSION: Our findings suggest that current suicide risk is common in patients with OCD and associated with various forms of pathology. Our work also provides further empirical data to support what is already known clinically: a worse clinical picture characterized by a high severity of OCD, high distress related to obsessions and compulsions, and the presence of comorbidities such as major depression and generalized anxiety disorder should be considered as relevant risk factors for suicide risk.
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Transtorno Obsessivo-Compulsivo , Adulto , Comorbidade , Transtorno da Personalidade Compulsiva , Estudos Transversais , Humanos , Transtorno Obsessivo-Compulsivo/epidemiologia , Prevalência , Tentativa de SuicídioRESUMO
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 analysis (polygenic risk scoring) of a subsample of 3,521 individuals. Obsessive symptomatology had a prevalence of 7.2% and compulsive symptomatology a prevalence of 8.6%. The proportion of individuals with OCS who had ever used cannabis was 23.4%, and of those with cannabis dependency was 2.7%, the latter figure higher than that in individuals with other psychiatric symptoms (hypomania, 2.6%; anxiety, 2.8%; depression, 2.3%), except psychosis (5.9%). Individuals with OCS who reported using cannabis had an increased genetic risk for cannabis dependence but not for OCD. We thus cannot know how the increased genetic risk of cannabis dependence in people with OCD is influenced by their pharmacological response to derivatives of THC. The results, however, suggest paths for future studies.
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Abstract Introduction It has been hypothesized that pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) etiology results from an abnormal immune response to streptococcal infection. There is evidence that the serotonergic system is involved in both obsessive-compulsive disorder (OCD) physiopathology and immunological processes. In the 5' promoter region of 5-HTT, gene encoding for the serotonin transporter we can find the 5-HTTLPR polymorphism that has been associated with OCD. Being PANDAS a disorder with OCD symptoms and likely immune abnormalities, 5-HTT polymorphisms may be particularly relevant for this disorder. Objective This study aimed to test the association between the 5-HT genotypes and the presence of serum antibodies in patients with PANDAS. Method We compared the genotype frequencies and serum anti-streptococcal, anti-neural, and anti-enolase antibodies titers between 56 patients with PANDAS and 20 healthy controls from Mexico and Cuba. Results Antibody titers were higher (anti-enolase, anti-streptococcal) in PANDAS patients compared to healthy controls. No differences in anti-neural antibody levels between both groups were detected. The anti-enolase and anti-neural antibody titer increased according to the polymorphism of the PANDAS patients as follows: LL >SL >SS. Discussion and conclusion This is the first study evaluating the association between the 5-HTTLPR genotypes and antibody titers in PANDAS patients. Associations between polymorphisms in serotonergic genes and immune response could provide valuable information about the interaction between both systems. Our results suggest an association between the S allele and elevated antibody levels in PANDAS patients.
Resumen Introducción Se ha hipotetizado que el trastorno pediátrico neuropsiquiátrico autoinmune asociado a estreptococo (PANDAS) es resultado de una respuesta inmune anormal a una infección estreptocócica. Existe evidencia de que el sistema serotoninérgico está involucrado tanto en la fisiopatología del trastorno obsesivo compulsivo (TOC) como en procesos inmunológicos. En la región promotora de 5-HTT, gen que codifica el transportador de serotonina, podemos encontrar el polimorfismo 5-HTTLPR que se ha asociado con el TOC. Siendo PANDAS un trastorno con síntomas de TOC y probables anormalidades inmunes, los polimorfismos de 5-HTT pueden ser relevantes en este trastorno. Objetivo Evaluar la asociación entre los genotipos de 5-HT y la presencia de anticuerpos séricos en pacientes con PANDAS. Método Comparamos la frecuencia de genotipos de 5-HT y los títulos de anticuerpos anti-estreptococo, antineurales y antienolasa en suero de 56 pacientes con PANDAS y 20 controles sanos de México y Cuba. Resultados Los títulos de anticuerpos antienolasa y antiestreptococo fueron mayores en pacientes con PANDAS en comparación con los controles. El título de anticuerpos antienolasa y antineural aumentó de acuerdo con el polimorfismo de los pacientes con PANDAS de la siguiente manera: LL >SL >SS. Discusión y conclusión Éste es el primer estudio que evalúa la asociación entre los genotipos de 5-HTTLPR y anticuerpos en pacientes con PANDAS. Las asociaciones entre polimorfismos de genes serotoninérgicos y la respuesta inmune podrían proporcionar información sobre la interacción entre ambos sistemas. Nuestros resultados sugieren una asociación entre el alelo S y niveles altos de anticuerpos en pacientes con PANDAS.
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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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Transtorno Bipolar/genética , Variações do Número de Cópias de DNA/genética , Predisposição Genética para Doença/genética , Esquizofrenia/genética , Irmãos , Adulto , Transtorno Bipolar/epidemiologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/epidemiologiaRESUMO
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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Metilação de DNA , Herança Multifatorial , Ideação Suicida , Tentativa de Suicídio , Epigênese Genética , HumanosRESUMO
INTRODUCTION: Bipolar disorder (BD) and obsessive compulsive disorder (OCD) are prevalent, comorbid, and disabling conditions, often characterized by early onset and chronic course. When comorbid, OCD and BD can determine a more pernicious course of illness, posing therapeutic challenges for clinicians. Available reports on prevalence and clinical characteristics of comorbidity between BD and OCD showed mixed results, likely depending on the primary diagnosis of analyzed samples. METHODS: We assessed prevalence and clinical characteristics of BD comorbidity in a large international sample of patients with primary OCD (n = 401), through the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) snapshot database, by comparing OCD subjects with vs without BD comorbidity. RESULTS: Among primary OCD patients, 6.2% showed comorbidity with BD. OCD patients with vs without BD comorbidity more frequently had a previous hospitalization (p < 0.001) and current augmentation therapies (p < 0.001). They also showed greater severity of OCD (p < 0.001), as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). CONCLUSION: These findings from a large international sample indicate that approximately 1 out of 16 patients with primary OCD may additionally have BD comorbidity along with other specific clinical characteristics, including more frequent previous hospitalizations, more complex therapeutic regimens, and a greater severity of OCD. Prospective international studies are needed to confirm our findings.
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Transtorno Bipolar/epidemiologia , Transtorno Obsessivo-Compulsivo/epidemiologia , Adulto , Comorbidade , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Sociedades MédicasRESUMO
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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Transtorno Bipolar/epidemiologia , Transtornos Mentais/epidemiologia , Esquizofrenia/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto , Transtorno Bipolar/genética , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/genética , Diagnóstico Duplo (Psiquiatria) , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Transtornos Mentais/genética , México , Pessoa de Meia-Idade , Esquizofrenia/genética , Transtornos Relacionados ao Uso de Substâncias/genética , Adulto JovemRESUMO
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 , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Esquizofrenia/epidemiologia , Transtorno Bipolar/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Mentais/epidemiologia , Esquizofrenia/genética , Transtorno Bipolar/genética , Diagnóstico Duplo (Psiquiatria) , Transtornos Relacionados ao Uso de Substâncias/genética , Predisposição Genética para Doença , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/epidemiologia , Estudo de Associação Genômica Ampla , Transtornos Mentais/genética , MéxicoRESUMO
BACKGROUND: Schizophrenia (SCZ) and dementia, often related, are two of the most common neuropsychiatric diseases; epidemiological studies have shown that SCZ patients present a 2-fold increased risk for dementia compared to non-schizophrenic individuals. We explored the presence of rare and novel damaging gene variants in patients diagnosed with late-onset dementia of Alzheimer's type (DAT) or SCZ. METHODS: We included 7 DAT and 12 SCZ patients and performed high-depth targeted sequencing of 184 genes. RESULTS: We found novel and rare damaging variants in 18 genes in these Mexican patients. Carriers of these variants showed extreme phenotypes, including, treatment-resistant SCZ or cognitive decline. Furthermore, we found a variation on ABCC1 as a possible link between psychosis and cognitive impairment. DISCUSSION: As an exploratory analysis, we report some interesting variations that should be corroborated in larger sample size studies.
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Doença de Alzheimer/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Demência/fisiopatologia , Esquizofrenia/fisiopatologia , Doença de Alzheimer/genética , Disfunção Cognitiva/genética , Demência/genética , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , México , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Fenótipo , Esquizofrenia/genéticaRESUMO
Abstract Background Schizophrenia (SCZ) and dementia, often related, are two of the most common neuropsychiatric diseases; epidemiological studies have shown that SCZ patients present a 2-fold increased risk for dementia compared to non-schizophrenic individuals. We explored the presence of rare and novel damaging gene variants in patients diagnosed with late-onset dementia of Alzheimers type (DAT) or SCZ. Methods We included 7 DAT and 12 SCZ patients and performed high-depth targeted sequencing of 184 genes. Results We found novel and rare damaging variants in 18 genes in these Mexican patients. Carriers of these variants showed extreme phenotypes, including, treatment-resistant SCZ or cognitive decline. Furthermore, we found a variation on ABCC1 as a possible link between psychosis and cognitive impairment. Discussion As an exploratory analysis, we report some interesting variations that should be corroborated in larger sample size studies.
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Humanos , Esquizofrenia/fisiopatologia , Demência/fisiopatologia , Doença de Alzheimer/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Fenótipo , Esquizofrenia/genética , Variação Genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Demência/genética , Sequenciamento de Nucleotídeos em Larga Escala , Doença de Alzheimer/genética , Disfunção Cognitiva/genética , MéxicoRESUMO
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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Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Transtorno Bipolar/genética , Simulação por Computador , Predisposição Genética para Doença/genética , Obesidade/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Índice de Massa Corporal , Feminino , Humanos , Masculino , MéxicoRESUMO
OBJECTIVE: An obsessive-compulsive disorder (OCD) subtype has been associated with streptococcal infections and is called pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS). The neuroanatomical characterization of subjects with this disorder is crucial for the better understanding of its pathophysiology; also, evaluation of these features as classifiers between patients and controls is relevant to determine potential biomarkers and useful in clinical diagnosis. This was the first multivariate pattern analysis (MVPA) study on an early-onset OCD subtype. METHODS: Fourteen pediatric patients with PANDAS were paired with 14 healthy subjects and were scanned to obtain structural magnetic resonance images (MRI). We identified neuroanatomical differences between subjects with PANDAS and healthy controls using voxel-based morphometry, diffusion tensor imaging (DTI), and surface analysis. We investigated the usefulness of these neuroanatomical differences to classify patients with PANDAS using MVPA. RESULTS: The pattern for the gray and white matter was significantly different between subjects with PANDAS and controls. Alterations emerged in the cortex, subcortex, and cerebellum. There were no significant group differences in DTI measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) or cortical features (thickness, sulci, volume, curvature, and gyrification). The overall accuracy of 75% was achieved using the gray matter features to classify patients with PANDAS and healthy controls. CONCLUSION: The results of this integrative study allow a better understanding of the neural substrates in this OCD subtype, suggesting that the anatomical gray matter characteristics could have an immune origin that might be helpful in patient classification.
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Doenças Autoimunes/classificação , Imagem de Tensor de Difusão/normas , Transtorno Obsessivo-Compulsivo/classificação , Infecções Estreptocócicas/classificação , Adolescente , Doenças Autoimunes/diagnóstico por imagem , Doenças Autoimunes/patologia , Criança , Interpretação Estatística de Dados , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Masculino , Análise Multivariada , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/patologia , Infecções Estreptocócicas/diagnóstico por imagem , Infecções Estreptocócicas/patologiaRESUMO
INTRODUCTION: In Mexico, the prevalence of neurocognitive disorders (NCDs) has increased in parallel with the increase in life expectancy. The E4 allele of the gene that encodes apolipoprotein E (APOE) is the main genetic risk factor for cognitive impairment. OBJECTIVE: To replicate the association of APOE-E4 allele with neurocognitive impairment in a Mexican population, as well as to implement a genetic risk-detection program with the APOE-E4 allele. METHOD: A program was structured for the detection of APOE-E4 allele risk in different recruiting centers from the central zone of the Mexican Republic, with three stages: recruitment and selection of candidates for the detection of the risk-allele, genetic risk analysis and delivery of results. RESULTS: In the genetic-association study to replicate the association with neurocognitive disorders by means of multivariate logistic models, the APOE-E4 allele increased the risk for cognitive impairment in the Mexican populations by approximately 6 % (OR: 5.83, p = 0.0025). In addition, 367 genetic risk results were delivered. CONCLUSIONS: The present program is the first one to be implemented in Mexico with the purpose to inform on a genetic risk factor for neurocognitive disorders in several centers of the country.
INTRODUCCIÓN: En México, la prevalencia de los trastornos neurocognitivos (TNC) han aumentado a la par del incremento en la esperanza de vida. El alelo E4 del gen que codifica la apolipoproteína E (APOE) es el principal factor de riesgo genético para deterioro neurocognitivo. OBJETIVO: Reproducir la asociación en población mexicana entre APOE-E4 y el deterioro neurocognitivo, así como implementar un programa de detección de riesgo genético con el alelo APOE-E4. MÉTODO: Se estructuró un programa de detección de riesgo basado en APO-EA en diferentes centros de reclutamiento en la zona centro de la República Mexicana, con tres etapas: reclutamiento y selección de los candidatos para la detección del alelo de riesgo, análisis del riesgo genético y entrega del resultado. RESULTADOS: El análisis de asociación genética para replicar la asociación con trastornos neurocognitivos mediante modelos logísticos multivariados mostró que el alelo E4 de APOE incrementó aproximadamente 6 % el riesgo en población mexicana (RM = 5.83, p = 0.0025). Se entregaron 367 resultados de riesgo genético. CONCLUSIONES: El presente programa es el primero en México implementado para dar a conocer un factor de riesgo genético para trastornos neurocognitivos en varios centros del país.
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Apolipoproteína E4/genética , Transtornos Cognitivos/genética , Disfunção Cognitiva/genética , Predisposição Genética para Doença , Alelos , Transtornos Cognitivos/epidemiologia , Disfunção Cognitiva/epidemiologia , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Abstract: Introduction: The study of autistic spectrum disorders (ASD) at the genetic level is extremely important to understand their origin. In Mexico, there are few works addressed from this perspective. Objective: We investigated the role of the Brain Derived Neurotrophic Factor (BDNF) gene variant rs6265 G/A for single nucleotide polymorphism analysis in Mexican children with ASD using a case-control association design. Method: We made a pilot study by case-control analysis adjusting by gender, age, and ancestry. Results: Our study found no association between the BDNF rs6265 gene polymorphism and ASD [p = .419, OR = 1.597 (.514, 4.967)] Discussion and conclusion: Worldwide, the results of case-control association studies with the rs6265 of BDNF are controversial and do not always replicate. This may be due to the ethnicity of our population and additional factors not studied in the present work. Our study suggests that the SNP rs6265 is not contributing for ASD susceptibility in Mexican population.
Resumen: Introducción: El estudio de los trastornos del espectro autista a nivel genético es de suma importancia para entender su origen. En México existen pocos trabajos abordados desde esta perspectiva. Objetivo: Investigamos el papel de la variante del gen rs6265 G/A del factor neurotrófico derivado del cerebro (BDNF) para el análisis del polimorfismo de un solo nucleótido en niños mexicanos con TEA por medio de un diseño de asociación de casos y controles. Método: Realizamos un estudio piloto mediante un análisis de casos y controles ajustando por género, edad y ancestría. Resultados: Nuestro estudio no encontró asociación entre el polimorfismo del gen BDNF rs6265 y TEA [p = .419, OR = 1.597 (.514, 4.967)]. Discusión y conclusión: A nivel mundial, los resultados de estudios de asociación caso-control con el rs6265 de BDNF son controvertidos y no siempre se replican. Esto puede deberse a la etnicidad de nuestra población y a otros factores no estudiados en el presente trabajo. El estudio sugiere que el SNP rs6265 no contribuye a la susceptibilidad al TEA en población mexicana.
RESUMO
OBJECTIVE: Obsessive-compulsive disorder (OCD) is associated with variable risk of suicide and prevalence of suicide attempt (SA). The present study aimed to assess the prevalence of SA and associated sociodemographic and clinical features in a large international sample of OCD patients. METHODS: A total of 425 OCD outpatients, recruited through the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network, were assessed and categorized in groups with or without a history of SA, and their sociodemographic and clinical features compared through Pearson's chi-squared and t tests. Logistic regression was performed to assess the impact of the collected data on the SA variable. RESULTS: 14.6% of our sample reported at least one SA during their lifetime. Patients with an SA had significantly higher rates of comorbid psychiatric disorders (60 vs. 17%, p<0.001; particularly tic disorder), medical disorders (51 vs. 15%, p<0.001), and previous hospitalizations (62 vs. 11%, p<0.001) than patients with no history of SA. With respect to geographical differences, European and South African patients showed significantly higher rates of SA history (40 and 39%, respectively) compared to North American and Middle-Eastern individuals (13 and 8%, respectively) (χ2=11.4, p<0.001). The logistic regression did not show any statistically significant predictor of SA among selected independent variables. CONCLUSIONS: Our international study found a history of SA prevalence of ~15% in OCD patients, with higher rates of psychiatric and medical comorbidities and previous hospitalizations in patients with a previous SA. Along with potential geographical influences, the presence of the abovementioned features should recommend additional caution in the assessment of suicide risk in OCD patients.