ANA GABRIELA HOUNIE
Projetos de Pesquisa
Unidades Organizacionais
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
9 resultados
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Agora exibindo 1 - 9 de 9
- Association study between functional polymorphisms in the TNF-alpha gene and obsessive-compulsive disorder(2012) CAPPI, Carolina; MUNIZ, Renan Kawano; SAMPAIO, Aline Santos; CORDEIRO, Quirino; BRENTANI, Helena; PALACIOS, Selma A.; MARQUES, Andrea H.; VALLADA, Homero; MIGUEL, Euripedes Constantino; GUILHERME, Luiza; HOUNIE, Ana GabrielaObsessive-compulsive disorder (OCD) is a prevalent psychiatric disorder of unknown etiology. However, there is some evidence that the immune system may play an important role in its pathogenesis. In the present study, two polymorphisms (rs1800795 and rs361525) in the promoter region of the cytokine tumor necrosis factor-alpha (TNFA) gene were genotyped in 183 OCD patients and in 249 healthy controls. The statistical tests were performed using the PLINK (R) software. We found that the A allele of the TNFA rs361525 polymorphism was significantly associated with OCD subjects, according to the allelic x association test (p=0.007). The presence of genetic markers, such as inflammatory cytokines genes linked to OCD, may represent additional evidence supporting the rote of the immune system in its pathogenesis.
article 8 Citação(ões) na Scopus The role of the VNTR functional polymorphism of the promoter region of the MAOA gene on psychiatric disorders(2011) NISHIOKA, Silvia A.; PERIN, Eduardo Aliende; SAMPAIO, Aline Santos; CORDEIRO, Quirino; CAPPI, Carolina; MASTROROSA, Rosana Savio; MORAIS, Ivanil A.; REIS, Viviane Neri de Souza; ROSARIO, Maria Conceicao do; HOUNIE, Ana GabrielaIntroduction: A functional variable number of tandem repeats (VNTR) polymorphism of the promoter region of the monoamine oxidase A (MAOA) gene has been described and many studies have investigated the association of this polymorphism with human behaviors, as well as with several psychiatric disorders. Objective: This study aimed to review the literature on the role of the VNTR functional polymorphism of the promoter region of the MAOA gene on the modulation of human behavior for the development of psychiatric disorders. Method: Searches on the Medline, Embase, Web of Science and PsycInfo databases were performed including works from January 1998 to June 2009. The words used were: ""MAOA and human behavior"" and ""MAOA and psychiatry"". Results: Several studies were found (N = 3,873). After the selection process, 109 papers were included in the review. There was found an association of MAOA low activity alleles with antisocial personality disorder, conduct disorder, ADHD, pathological gambling, and substance abuse. High activity alleles were associated with neuroticism, anorexia nervosa and depression and anxiety disorders. There was no association between the MAOA polymorphisms and bipolar disorder and schizophrenia. Discussion: The main findings, summarized in this paper, support a role of MAOA VNTR polymorphism in some psychiatric disorders although some divergences were found due to methodological difficulties in genetic studies. In general, the studies associated the low activity alleles with impulsivity and aggressive behavior (""hyperactive behaviors""), and the high activity alleles of the gene with ""hypoactive behaviors"", such as depression and anxiety, which demonstrates a modulation of the MAOA enzyme in ""hyperactive"" and ""hypoactive"" disorders.- Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations in immunological and neurodevelopmental pathways(2016) CAPPI, C.; BRENTANI, H.; LIMA, L.; SANDERS, S. J.; ZAI, G.; DINIZ, B. J.; REIS, V. N. S.; HOUNIE, A. G.; ROSARIO, M. Conceicao do; MARIANI, D.; REQUENA, G. L.; PUGA, R.; SOUZA-DURAN, F. L.; SHAVITT, R. G.; PAULS, D. L.; MIGUEL, E. C.; FERNANDEZ, T. V.Studies of rare genetic variation have identified molecular pathways conferring risk for developmental neuropsychiatric disorders. To date, no published whole-exome sequencing studies have been reported in obsessive-compulsive disorder (OCD). We sequenced all the genome coding regions in 20 sporadic OCD cases and their unaffected parents to identify rare de novo (DN) single-nucleotide variants (SNVs). The primary aim of this pilot study was to determine whether DN variation contributes to OCD risk. To this aim, we evaluated whether there is an elevated rate of DN mutations in OCD, which would justify this approach toward gene discovery in larger studies of the disorder. Furthermore, to explore functional molecular correlations among genes with nonsynonymous DN SNVs in OCD probands, a protein-protein interaction (PPI) network was generated based on databases of direct molecular interactions. We applied Degree-Aware Disease Gene Prioritization (DADA) to rank the PPI network genes based on their relatedness to a set of OCD candidate genes from two OCD genome-wide association studies (Stewart et al., 2013; Mattheisen et al., 2014). In addition, we performed a pathway analysis with genes from the PPI network. The rate of DN SNVs in OCD was 2.51 x 10(-8) per base per generation, significantly higher than a previous estimated rate in unaffected subjects using the same sequencing platform and analytic pipeline. Several genes harboring DN SNVs in OCD were highly interconnected in the PPI network and ranked high in the DADA analysis. Nearly all the DN SNVs in this study are in genes expressed in the human brain, and a pathway analysis revealed enrichment in immunological and central nervous system functioning and development. The results of this pilot study indicate that further investigation of DN variation in larger OCD cohorts is warranted to identify specific risk genes and to confirm our preliminary finding with regard to PPI network enrichment for particular biological pathways and functions.
- COMT and MAO-A Polymorphisms and Obsessive-Compulsive Disorder: A Family-Based Association Study(2015) SAMPAIO, Aline Santos; HOUNIE, Ana Gabriela; PETRIBU, Katia; CAPPI, Carolina; MORAIS, Ivanil; VALLADA, Homero; ROSARIO, Maria Conceicao do; STEWART, S. Evelyn; FARGENESS, Jesen; MATHEWS, Carol; ARNOLD, Paul; HANNA, Gregory L.; RICHTER, Margaret; KENNEDY, James; FONTENELLE, Leonardo; PEREIRA, Carlos Alberto de Braganca; PAULS, David L.; MIGUEL, Euripedes ConstantinoObjective Obsessive-compulsive disorder (OCD) is a common and debilitating psychiatric illness. Although a genetic component contributes to its etiology, no single gene or mechanism has been identified to the OCD susceptibility. The catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A) genes have been investigated in previous OCD studies, but the results are still unclear. More recently, Taylor (2013) in a comprehensive meta-analysis of genetic association studies has identified COMT and MAO-A polymorphisms involved with OCD. In an effort to clarify the role of these two genes in OCD vulnerability, a family-based association investigation was performed as an alternative strategy to the classical case-control design. Methods Transmission disequilibrium analyses were performed after genotyping 13 single-nucleotide polymorphisms (eight in COMT and five in MAO-A) in 783 OCD trios (probands and their parents). Four different OCD phenotypes (from narrow to broad OCD definitions) and a SNP x SNP epistasis were also analyzed. Results OCD, broad and narrow phenotypes, were not associated with any of the investigated COMT and MAO-A polymorphisms. In addition, the analyses of gene-gene interaction did not show significant epistatic influences on phenotype between COMT and MAO-A. Conclusions The findings do not support an association between DSM-IV OCD and the variants of COMT or MAO-A. However, results from this study cannot exclude the contribution of these genes in the manifestation of OCD. The evaluation of broader spectrum phenotypes could help to understand the role of these and other genes in the pathophysiology of OCD and its spectrum disorders.
- An Inherited Small Microdeletion at 15q13.3 in a Patient with Early- Onset Obsessive-Compulsive Disorder(2014) CAPPI, Carolina; HOUNIE, Ana Gabriela; MARIANI, Daniel B.; DINIZ, Juliana Belo; SILVA, Aderbal R. T.; REIS, Viviane N. S.; BUSSO, Ariane F.; SILVA, Amanda Goncalves; FIDALGO, Felipe; ROGATTO, Silvia Regina; MIGUEL, Euripedes C.; KREPISCHI, Ana C.; BRENTANI, HelenaCopy number variations (CNVs) have been previously associated with several different neurodevelopmen al psychiatric disorders, such as autism, schizophrenia, and attention deficit hyperactivity disorder (ADHD). The present study consisted of pilot genorne-wide screen for CNVs in a cohort of 16 patients with early-onset obsessive-compulsive disorder (OCD) and 2 mentally healthy individuals, using array-based comparative enomic hybridization (aCGH) on 44K arrays. A small rare nal inherited microdeletion (-64 kb) was identified in chromosome 15q13.3 of one male patient with very early onset have OCD. The deletion encompassed part of the FA/IN1 gene, which is involved with the glutamatergic system This finding supports the hypothesis of a complex network of several genes expressed in the brain cant ibuting for h genetic risk of OCD, and also supports the glutamatergic involvement in OCD, which has been previsously reported in the literature.
article 116 Citação(ões) na Scopus Gender differences in obsessive-compulsive disorder: a literature review(2011) MATHIS, Maria Alice de; ALVARENGA, Pedro de; FUNARO, Guilherme; TORRESAN, Ricardo Cezar; MORAES, Ivanil; TORRES, Albina Rodrigues; ZILBERMAN, Monica L.; HOUNIE, Ana GabrielaIntroduction: Obsessive-compulsive disorder (OCD) is a heterogeneous condition, in which subtypes have been proposed. Previous studies suggested that gender plays a relevant role in OCD phenotypic expression. This study aimed to review the literature on gender differences in clinical, genetic or familial aspects of OCD. Method: A conventional review was conducted, including all papers that investigated demographic, clinical, and genetic aspects of OCD according to gender. The search was based on data available in Medline and PsycINFO databases in the last 20 years, using as keywords: obsessive-compulsive disorder; and: gender, sex, male, female, demographic characteristics, clinical features, clinical characteristics, genetic, genes, genetics gender OCD, genes OCD, genes OCD males, genes OCD females. Results: Sixty three of 487 phenotypical and genetics studies were selected. Most studies indicate that male patients are more likely than females to be single, present early onset of symptoms and chronic course of the disorder, greater social impairment, more sexual-religious and aggressive symptoms, and greater comorbidity with tic and substance use disorders. Female patients present more contamination/cleaning symptoms and greater comorbidity with eating and impulse-control disorders. Genetic and family studies are inconclusive, but suggest that gender may play a role in the disease expression. Conclusions: Gender is a relevant factor that should be taken into account when evaluating OCD patients. More studies are necessary to determine whether in fact it defines a homogeneous and particular group in OCD.- Testing allele homogeneity: the problem of nested hypotheses(2012) IZBICKI, Rafael; FOSSALUZA, Victor; HOUNIE, Ana Gabriela; NAKANO, Eduardo Yoshio; PEREIRA, Carlos Alberto de BragancaBackground: The evaluation of associations between genotypes and diseases in a case-control framework plays an important role in genetic epidemiology. This paper focuses on the evaluation of the homogeneity of both genotypic and allelic frequencies. The traditional test that is used to check allelic homogeneity is known to be valid only under Hardy-Weinberg equilibrium, a property that may not hold in practice. Results: We first describe the flaws of the traditional (chi-squared) tests for both allelic and genotypic homogeneity. Besides the known problem of the allelic procedure, we show that whenever these tests are used, an incoherence may arise: sometimes the genotypic homogeneity hypothesis is not rejected, but the allelic hypothesis is. As we argue, this is logically impossible. Some methods that were recently proposed implicitly rely on the idea that this does not happen. In an attempt to correct this incoherence, we describe an alternative frequentist approach that is appropriate even when Hardy-Weinberg equilibrium does not hold. It is then shown that the problem remains and is intrinsic of frequentist procedures. Finally, we introduce the Full Bayesian Significance Test to test both hypotheses and prove that the incoherence cannot happen with these new tests. To illustrate this, all five tests are applied to real and simulated datasets. Using the celebrated power analysis, we show that the Bayesian method is comparable to the frequentist one and has the advantage of being coherent. Conclusions: Contrary to more traditional approaches, the Full Bayesian Significance Test for association studies provides a simple, coherent and powerful tool for detecting associations.
- Estudos de associação genética no transtorno obsessivo-compulsivo(2013) SAMPAIO, Aline Santos; LINS, Rita Marcia Pacheco; DALTRO-OLIVEIRA, Renato; QUARANTINI, Lucas de Castro; ROSARIO, Maria Conceicao do; MIGUEL, Euripedes Constantino; HOUNIE, Ana GabrielaBackground: Obsessive-compulsive disorder (OCD) segregates in families. It follows a complex model of genetic transmission, which involves the influence of several small effect genes interacting with the environment. Methods: A systematic review of genetic association studies in OCD was performed. Articles published until 2012 were searched in the databases PubMed, Embase and SciELO using the terms of MeSH and its associates or synonyms for ""obsessive-compulsive disorder"", ""gene"" and ""genetic association studies"". Results: We selected 105 papers and described their main results grouped as genes related to: serotonin, dopamine, glutamate, GABA, white matter, immune system, hormones and other genes. Conclusion: There is high variability between findings of association studies among the several candidate genes studied in OCD. Glutamate-related genes are promising candidates for OCD, but there is no conclusive association between any of the candidate genes studied and OCD. Association studies with large sample size, evaluation of more homogeneous subgroups of phenotype and meta-analyses are still needed.
- Brain derived neurotrophic factor mediated learning, fear acquisition and extinction as targets for developing novel treatments for anxiety(2016) OLIVEIRA, Karina Soares de; HOUNIE, Ana Gabriela; CAPPI, Carolina; DINIZ, Juliana BeloABSTRACT Anxiety and obsessive-compulsive related disorders are highly prevalent and disabling disorders for which there are still treatment gaps to be explored. Fear is a core symptom of these disorders and its learning is highly dependent on the activity of the neurotrophin brain-derived neurotrophic factor (BDNF). Should BDNF-mediated fear learning be considered a target for the development of novel treatments for anxiety and obsessive-compulsive related disorders? We review the evidence that suggests that BDNF expression is necessary for the acquisition of conditioned fear, as well as for the recall of its extinction. We describe the findings related to fear learning and genetic/epigenetic manipulation of Bdnf expression in animals and BDNF allelic variants in humans. Later, we discuss how manipulation of BDNF levels represents a promising potential treatment target that may increase the benefits of therapies that extinguish previously conditioned fear.