ANA GABRIELA HOUNIE
Projetos de Pesquisa
Unidades Organizacionais
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
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.- 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.
- 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.
- 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 RodriguesObjective. 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.
- Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD(2015) YU, Dongmei; MATHEWS, Carol A.; SCHARF, Jeremiah M.; NEALE, Benjamin M.; DAVIS, Lea K.; GAMAZON, Eric R.; DERKS, Eske M.; EVANS, Patrick; EDLUND, Christopher K.; CRANE, Jacquelyn; OSIECKI, Lisa; RENNER, Tobias; REUS, Victor I.; RICHTER, Margaret A.; RIDDLE, Mark A.; ROBERTSON, Mary M.; ROMERO, Roxana; ROSARIO, Maria C.; ROSENBERG, David; RUHRMANN, Stephan; SABATTI, Chiara; GALLAGHER, Patience; SALVI, Erika; SAMPAIO, Aline S.; SAMUELS, Jack; SANDOR, Paul; SERVICE, Susan K.; SHEPPARD, Brooke; SINGER, Harvey S.; SMIT, Jan H.; STEIN, Dan J.; STRENGMAN, Eric; GERBER, Gloria; TISCHFIELD, Jay A.; TURIEL, Maurizio; DUARTE, Ana V. Valencia; VALLADA, Homero; VEENSTRA-VANDERWEELE, Jeremy; WALITZA, Susanne; WANG, Ying; WEALE, Mike; WEISS, Robert; WENDLAND, Jens R.; HADDAD, Stephen; WESTENBERG, Herman G. M.; SHUGART, Yin Yao; HOUNIE, Ana G.; MIGUEL, Euripedes C.; NICOLINI, Humberto; WAGNER, Michael; RUIZ-LINARES, Andres; CATH, Danielle C.; MCMAHON, William; POSTHUMA, Danielle; ILLMANN, Cornelia; OOSTRA, Ben A.; NESTADT, Gerald; ROUTEAU, Guy A.; PURCELL, Shaun; JENIKE, Michael A.; HEUTINK, Peter; HANNA, Gregory L.; CONTI, David V.; ARNOLD, Paul D.; FREIMER, Nelson B.; MCGRATH, Lauren M.; STEWART, Evelyn; KNOWLES, James A.; COX, Nancy J.; PAULS, David L.; MAYERFELD, Catherine; AREPALLI, Sampath; BARLASSINA, Cristina; BARR, Cathy L.; BELLODI, Laura; BENARROCH, Fortu; BERRIO, Gabriel Bedoya; BIENVENU, O. Joseph; BLACK, Donald W.; BLOCH, Michael H.; BRENTANI, Helena; BRUUN, Ruth D.; BUDMAN, Cathy L.; CAMARENA, Beatriz; CAMPBELL, Desmond D.; CAPPI, Carolina; SILGADO, Julio C. Cardona; CAVALLINI, Maria C.; CHAVIRA, Denise A.; CHOUINARD, Sylvain; COOK, Edwin H.; COOKSON, M. R.; CORIC, Vladimir; CULLEN, Bernadette; CUSI, Daniete; DELORME, Richard; DENYS, Damiaan; DION, Yves; EAPEN, Valsama; EGBERTS, Karin; FALKAI, Peter; FERNANDEZ, Thomas; FOURNIER, Eduardo; GARRIDO, Helena; GELLER, Daniel; GILBERT, Donald L.; GIRARD, Simon L.; GRABE, Hans J.; GRADOS, Marco A.; GREENBERG, Benjamin D.; GROSS-TSUR, Varda; GRUENBLATT, Edna; HARDY, John; HEIMAN, Gary A.; HEMMINGS, Sian M. J.; HERRERA, Luis D.; HEZEL, Dianne M.; HOEKSTRA, Pieter J.; JANKOVIC, Joseph; KENNEDY, James L.; KING, Robert A.; KONKASHBAEV, Anuar I.; KREMEYER, Barbara; KURLAN, Roger; LANZAGORTA, Nuria; LEBOYER, Marion; LECKMAN, James F.; LENNERTZ, Leonhard; LIU, Chunyu; LOCHNER, Christine; LOWE, Thomas L.; LUPOLI, Sara; MACCIARDI, Fabio; MAIER, Wolfgang; MANUNTA, Paolo; MARCONI, Maurizio; MCCRACKEN, James T.; RESTREPO, Sandra C. Mesa; MOESSNER, Rainald; MOORJANI, Priya; MORGAN, Jubel; MULLER, Heike; MURPHY, Dennis L.; NAARDEN, Allan L.; NURMI, Erika; OCHOA, William Cornejo; OPHOFF, Roel A.; PAKSTIS, Andrew J.; PATO, Michele T.; PATO, Carlo N.; PIACENTINI, John; PITTENGER, Christopher; POLLAK, Yehuda; RAUCH, Scott L.Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD. Method: The authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders. Results: Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders Polygenic score analyses identified a significant polygenic component for OCD (p=2x10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01). Conclusions: Previous work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring burette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.
- 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.
- Copy Number Variation in Obsessive-Compulsive Disorder and Tourette Syndrome: A Cross-Disorder Study(2014) MCGRATH, Lauren M.; YU, Dongmei; MARSHALL, Christian; DAVIS, Lea K.; THIRUVAHINDRAPURAM, Bhooma; LI, Bingbin; CAPPI, Carolina; GERBER, Gloria; WOLF, Aaron; SCHROEDER, Frederick A.; OSIECKI, Lisa; O'DUSHLAINE, Colm; KIRBY, Andrew; ILLMANN, Cornelia; HADDAD, Stephen; GALLAGHER, Patience; FAGERNESS, Jesen A.; BARR, Cathy L.; BELLODI, Laura; BENARROCH, Fortu; BIENVENU, O. Joseph; BLACK, Donald W.; BLOCH, Michael H.; BRUUN, Ruth D.; BUDMAN, Cathy L.; CAMARENA, Beatriz; CATH, Danielle C.; CAVALLINI, Maria C.; CHOUINARD, Sylvain; CORIC, Vladimir; CULLEN, Bernadette; DELORME, Richard; DENYS, Damiaan; DERKS, Eske M.; DION, Yves; ROSARIO, Maria C.; EAPEN, Valsama; EVANS, Patrick; FALKAI, Peter; FERNANDEZ, Thomas V.; GARRIDO, Helena; GELLER, Daniel; GRABE, Hans J.; GRADOS, Marco A.; GREENBERG, Benjamin D.; GROSS-TSUR, Varda; GRUENBLATT, Edna; HEIMAN, Gary A.; HEMMINGS, Sian M. J.; HERRERA, Luis D.; HOUNIE, Ana G.; JANKOVIC, Joseph; KENNEDY, James L.; KING, Robert A.; KURLAN, Roger; LANZAGORTA, Nuria; LEBOYER, Marion; LECKMAN, James F.; LENNERTZ, Leonhard; LOCHNER, Christine; LOWE, Thomas L.; LYON, Gholson J.; MACCIARDI, Fabio; MAIER, Wolfgang; MCCRACKEN, James T.; MCMAHON, William; MURPHY, Dennis L.; NAARDEN, Allan L.; NEALE, Benjamin M.; NURMI, Erika; PAKSTIS, Andrew J.; PATO, Michele T.; PATO, Carlos N.; PIACENTINI, John; PITTENGER, Christopher; POLLAK, Yehuda; REUS, Victor I.; RICHTER, Margaret A.; RIDDLE, Mark; ROBERTSON, Mary M.; ROSENBERG, David; ROULEAU, Guy A.; RUHRMANN, Stephan; SAMPAIO, Aline S.; SAMUELS, Jack; SANDOR, Paul; SHEPPARD, Brooke; SINGER, Harvey S.; SMIT, Jan H.; STEIN, Dan J.; TISCHRIELD, Jay A.; VALLADA, Homero; VEENSTRA-VANDERWEELE, Jeremy; WALITZA, Susanne; WANG, Ying; WENDFAND, Jens R.; SHUGART, Yin Yao; MIGUEL, Euripedes C.; NICOLINI, Humberto; OOSTRA, Ben A.; MOESSNER, Rainald; WAGNER, Michael; RUIZ-LINARES, Andres; HEUTINK, Peter; NESTADT, Gerald; FREIMER, Nelson; PETRYSHEN, Tracey; POSTHUMA, Danielle; JENIKE, Michael A.; COX, Nancy J.; HANNA, Gregory L.; BRENTANI, Helena; SCHERER, Stephen W.; ARNOLD, Paul D.; STEWART, S. Evelyn; MATHEWS, Carol A.; KNOWLES, James A.; COOK, Edwin H.; PAULS, David L.; WANG, Kai; SCHARF, Jeremiah M.Objective: Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. Method: The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. Results: Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p = .09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 case patient deletions: 0 control deletions, p = .08 in the current study, p = .025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support for the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in individuals with autism or schizophrenia (2-4%). Conclusion: Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes.