ANA GABRIELA HOUNIE

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Projetos de Pesquisa
Unidades Organizacionais
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina

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Agora exibindo 1 - 10 de 17
  • article 143 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.
  • 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 248 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 55 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 50 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.
  • article 20 Citação(ões) na Scopus
    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 Constantino
    Objective 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.
  • article 60 Citação(ões) na Scopus
    Clinical features of tic-related obsessive-compulsive disorder: results from a large multicenter study
    (2012) ALVARENGA, Pedro Gomes de; MATHIS, Maria Alice de; ALVES, Anna Claudia Dominguez; ROSARIO, Maria Conceicao do; FOSSALUZA, Victor; HOUNIE, Ana Gabriela; MIGUEL, Euripedes Constantino; TORRES, Albina Rodrigues
    Objective. To evaluate the clinical features of obsessive-compulsive disorder (OCD) patients with comorbid tic disorders (TD) in a large, multicenter, clinical sample. Method. A cross-sectional study was conducted that included 813 consecutive OCD outpatients from the Brazilian OCD Research Consortium and used several instruments of assessment, including the Yale-Brown Obsessive-Compulsive Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, the Yale Global Tic Severity Scale (YGTSS), the USP Sensory Phenomena Scale, and the Structured Clinical Interview for DSM-IV Axis I Disorders. Results. The sample mean current age was 34.9 years old (SE 0.54), and the mean age at obsessive-compulsive symptoms (OCS) onset was 12.8 years old (SE 0.27). Sensory phenomena were reported by 585 individuals (72% of the sample). The general lifetime prevalence of TD was 29.0% (n=236), with 8.9% (n=72) presenting Tourette syndrome, 17.3% (n=5141) chronic motor tic disorder, and 2.8% (n=523) chronic vocal tic disorder. The mean tic severity score, according to the YGTSS, was 27.2 (SE 1.4) in the OCD1TD group. Compared to OCD patients without comorbid TD, those with TD (OCD1TD group, n=236) were more likely to be males (49.2% vs. 38.5%, p<005) and to present sensory phenomena and comorbidity with anxiety disorders in general: separation anxiety disorder, social phobia, specific phobia, generalized anxiety disorder, post-traumatic stress disorder, attention-deficit hyperactivity disorder, impulse control disorders in general, and skin picking. Also, the ""aggressive,"" ""sexual/religious,"" and ""hoarding"" symptom dimensions were more severe in the OCD+TD group. Conclusion. Tic-related OCD may constitute a particular subgroup of the disorder with specific phenotypical characteristics, but its neurobiological underpinnings remain to be fully disentangled.