ANA GABRIELA HOUNIE

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LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina

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  • article 140 Citação(ões) na Scopus
    Sensory phenomena associated with repetitive behaviors in obsessive-compulsive disorder: An exploratory study of 1001 patients
    (2012) FERRAO, Ygor Arzeno; SHAVITT, Roseli Gedanke; PRADO, Helena; FONTENELLE, Leonardo F.; MALAVAZZI, Dante Marino; MATHIS, Maria Alice de; HOUNIE, Ana Gabriela; MIGUEL, Euripedes Constantino; ROSARIO, Maria Conceicao do
    A substantial number of patients with obsessive-compulsive disorder (OCD) report compulsions that are preceded not by obsessions but by subjective experiences known as sensory phenomena. This study aimed to investigate the frequency, severity, and age at onset of sensory phenomena in OCD, as well as to compare OCD patients with and without sensory phenomena in terms of clinical characteristics. We assessed 1,001 consecutive OCD patients, using instruments designed to evaluate the frequency/severity of OC symptoms, tics, anxiety, depression, level of insight and presence/severity of sensory phenomena. All together, 651 (65.0%) subjects reported at least one type of sensory phenomena preceding the repetitive behaviors. Considering the sensory phenomena subtypes, 371 (57.0%) patients had musculoskeletal sensations, 519 (79.7%) had externally triggered ""just-right"" perceptions, 176 (27.0%) presented internally triggered ""just right,"" 144 (22.1%) had an ""energy release,"" and 240 (36.9%) patients had an ""urge only"" phenomenon. Sensory phenomena were described as being as more severe than were obsessions by 102(15.7%) patients. Logistic regression analysis showed that the following characteristics were associated with the presence of sensory phenomena: higher frequency and greater severity of the symmetry/ordering/arranging and contamination/washing symptom dimensions; comorbid Tourette syndrome, and a family history of tic disorders. These data suggest that sensory phenomena constitute a poorly understood psychopathological aspect of OCD that merits further investigation.
  • conferenceObject
    Association between MAO-A and Obsessive-Compulsive Disorder related phenotypes
    (2013) SAMPAIO, A. S.; HOUNIE, A. G.; PETRIBU, K.; CAPPI, C.; MORAIS, I. A.; QUARANTINI, L. C.; FILHO, H. P. V.; ROSARIO, M. da Conceicao do; STEWART, S. E.; FARGENESS, J.; MATTHEWS, C.; ARNOLD, P.; RICHTER, M.; KENNEDY, J.; HANNA, G. L.; PAULS, D. L.; MIGUEL FILHO, E. C.
  • article 24 Citação(ões) na Scopus
    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 Gabriela
    Obsessive-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.
  • conferenceObject
    Does Inflammation Play a Role in Obsessive-Compulsive Disorder?
    (2013) SILVERMAN, Marni; CASSAB, Raony; MUNIZ, Renan; SHAVITT, Roseli G.; TOLEDO, Maria Cecilia; CAPPI, Carolina; THAYER, Julian; MATHIS, Maria Alice de; DINIZ, Juliana B.; HOEXTER, Marcelo Q.; D'ALCANTE, Carina C.; BORCATO, Sonia; HOUNIE, Ana G.; WHITFIELD, Jessie; BELYAVSKAYA, Elena; STERNBERG, Esther; MIGUEL, Euripedes; MARQUES, Andrea H.
  • conferenceObject
    Whole-exome Sequencing in Obsessive-compulsive Disorder Identifies Rare Mutations and Immunological Pathways
    (2014) CAPPI, Carolina; BRENTANI, Helena; LIMA, Leandro; SANDERS, Stephan J.; DINIZ, Juliana; WALKER, Michael; REIS, Viviane N. S.; HOUNIE, Ana G.; MARIANI, Daniel; OKI, Fabio H.; SHAVITT, Roseli G.; PAULS, David L.; MIGUEL, Euripedes C.; FERNANDEZ, Thomas V.
  • article 245 Citação(ões) na Scopus
    Genome-wide association study of obsessive-compulsive disorder
    (2013) STEWART, S. E.; YU, D.; SCHARF, J. M.; NEALE, B. M.; FAGERNESS, J. A.; MATHEWS, C. A.; ARNOLD, P. D.; EVANS, P. D.; GAMAZON, E. R.; OSIECKI, L.; MCGRATH, L.; HADDAD, S.; CRANE, J.; HEZEL, D.; ILLMAN, C.; MAYERFELD, C.; KONKASHBAEV, A.; LIU, C.; PLUZHNIKOV, A.; TIKHOMIROV, A.; EDLUND, C. K.; RAUCH, S. L.; MOESSNER, R.; FALKAI, P.; MAIER, W.; RUHRMANN, S.; GRABE, H-J; LENNERTZ, L.; WAGNER, M.; BELLODI, L.; CAVALLINI, M. C.; RICHTER, M. A.; COOK JR., E. H.; KENNEDY, J. L.; ROSENBERG, D.; STEIN, D. J.; HEMMINGS, S. M. J.; LOCHNER, C.; AZZAM, A.; CHAVIRA, D. A.; FOURNIER, E.; GARRIDO, H.; SHEPPARD, B.; UMANA, P.; MURPHY, D. L.; WENDLAND, J. R.; VEENSTRA-VANDERWEELE, J.; DENYS, D.; BLOM, R.; DEFORCE, D.; NIEUWERBURGH, F. Van; WESTENBERG, H. G. M.; WALITZA, S.; EGBERTS, K.; RENNER, T.; MIGUEL, E. C.; CAPPI, C.; HOUNIE, A. G.; ROSARIO, M. Conceicao do; SAMPAIO, A. S.; VALLADA, H.; NICOLINI, H.; LANZAGORTA, N.; CAMARENA, B.; DELORME, R.; LEBOYER, M.; PATO, C. N.; PATO, M. T.; VOYIAZIAKIS, E.; HEUTINK, P.; CATH, D. C.; POSTHUMA, D.; SMIT, J. H.; SAMUELS, J.; BIENVENU, O. J.; CULLEN, B.; FYER, A. J.; GRADOS, M. A.; GREENBERG, B. D.; MCCRACKEN, J. T.; RIDDLE, M. A.; WANG, Y.; CORIC, V.; LECKMAN, J. F.; BLOCH, M.; PITTENGER, C.; EAPEN, V.; BLACK, D. W.; OPHOFF, R. A.; STRENGMAN, E.; CUSI, D.; TURIEL, M.; FRAU, F.; MACCIARDI, F.; GIBBS, J. R.; COOKSON, M. R.; SINGLETON, A.; HARDY, J.; CRENSHAW, A. T.; PARKIN, M. A.; MIREL, D. B.; CONTI, D. V.; PURCELL, S.; NESTADT, G.; HANNA, G. L.; JENIKE, M. A.; KNOWLES, J. A.; COX, N.; PAULS, D. L.
    Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469 410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two P-values were located within DLGAP1 (P = 2.49 x 10(-6) and P = 3.44 x 10(-6)), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value = 3.84 x 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 x 10(-5), losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation QTLs (P < 0.001) and frontal lobe expression quantitative trait loci (eQTLs) (P = 0.001) was observed within the top-ranked SNPs (P < 0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.
  • 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 Gabriela
    Introduction: 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.
  • article 54 Citação(ões) na Scopus
    Comorbid major depression in obsessive-compulsive disorder patients
    (2011) QUARANTINI, Lucas C.; TORRES, Albina Rodrigues; SAMPAIO, Aline S.; FOSSALUZA, Victor; MATHIS, Maria Alice de; ROSARIO, Maria Conceicao do; FONTENELLE, Leonardo F.; FERRAO, Ygor A.; CORDIOLI, Aristides Volpato; PETRIBU, Katia; HOUNIE, Ana G.; MIGUEL, Euripedes C.; SHAVITT, Roseli G.; KOENEN, Karestan C.
    Although major depressive disorder (MDD) has been consistently considered the most frequent complication of obsessive-compulsive disorder (OCD), little is known about the clinical characteristics of patients with both disorders. This study assessed 815 Brazilian OCD patients using a comprehensive psychiatric evaluation. Clinical and demographic variables, including OCD symptom dimensions, were compared among OCD patients with and without MDD. Our findings showed that prevalence rates of current MDD (32%) and lifetime MDD (67.5%) were similar for both sexes in this study. In addition, patients with comorbid MDD had higher severity scores of OCD symptoms. There was no preferential association of MDD with any particular OCD symptom dimension. This study supports the notion that depressed OCD patients present more severe general psychopathology.
  • article 17 Citação(ões) na Scopus
    Clinical predictors of quality of life in a large sample of adult obsessive-compulsive disorder outpatients
    (2018) VELLOSO, Patricia; PICCINATO, Cinthia; FERRAO, Ygor; PERIN, Eduardo Aliende; CESAR, Raony; FONTENELLE, Leonardo F.; HOUNIE, Ana G.; ROSARIO, Maria Conceicao do
    Background: OCD causes impairment in different areas of the patients' quality of life (QoL), such as sociability, family relationships, and occupational performance. The literature has emphasized the relevance of assessing QoL as a critical outcome in mental health studies. Aims: The aim of this study was to investigate sociodemographic and clinical predictors of QoL, including treatment response, in a large sample of OCD subjects. Procedures: 575 adult OCD outpatients were interviewed as part of the Brazilian OCD Consortium (CTOC). A smaller number of subjects (N = 143) participated on a clinical trial conducted by one of the CTOC sites. Results: OCD patients were more impaired in their QoL when compared to the Brazilian normative data. Obsessive-compulsive symptoms (OCS) severity had significant correlations with all Medical Outcome Short Form questionnaire (SF-36) domains. Different OCS dimensions had specific correlations with each SF-36 domain. OCS, depression and anxiety severity significantly increased the impairment risk for the SF-36 domains. Suicidality increased the relative risks for impairment in the Role-Functioning and the Vitality domains by 51% and 17%, respectively. There was a significant improvement in some SF-36 dimensions after treatment. Conclusions: QoL domains are highly compromised in OCD patients. Each SF-36 domain had distinct associations with sociodemographic and clinical variables, including OCS dimensions, suicidality and treatment response. These findings emphasize the OCD heterogeneity and the need for including QoL assessment in clinical practice and research studies.
  • article 49 Citação(ões) na Scopus
    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.