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Obsessive-Compulsive Disorder: HELP
Articles by Laura Bellodi
Based on 11 articles published since 2008
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Between 2008 and 2019, L. Bellodi wrote the following 11 articles about Obsessive-Compulsive Disorder.
 
+ Citations + Abstracts
1 Article Planning functioning and impulsiveness in obsessive-compulsive disorder. 2018

Martoni, Riccardo Maria / de Filippis, Roberta / Cammino, Stefania / Giuliani, Mattia / Risso, Gaia / Cavallini, Maria Cristina / Bellodi, Laura. ·Department of Clinical Neurosciences, San Raffaele Scientific Institute, Via Stamira D'Ancona, 20, 20127, Milan, Italy. · Department of Clinical Neurosciences, San Raffaele Scientific Institute, Via Stamira D'Ancona, 20, 20127, Milan, Italy. defilippis.roberta@yahoo.it. · Faculty of Psychology, University Vita-Salute San Raffaele, Milan, Italy. ·Eur Arch Psychiatry Clin Neurosci · Pubmed #28466133.

ABSTRACT: Planning ability (PA) is a key aspect of cognitive functioning and requires subjects to identify and organise the necessary steps to achieve a goal. Despite the central role of executive dysfunction in patients with obsessive-compulsive disorder (OCD), deficits in PA have been investigated leading to contrasting results. Given these inconsistencies, the main aim of our work is to give a deeper and clearer understanding of PA in OCD patients. Moreover, we are interested in investigating the relationship between PAs and impulsivity traits and other clinical variables. Sixty-eight OCD patients and 68 healthy controls (HCs) matched for sex and age were assessed through the Stocking of Cambridge (SoC), a computerised version of the Tower of London. We examined planning sub-components for each difficulty levels (from 2 to 5 minimum moves). Our results showed that OCD patients needed longer initial thinking time than HCs during the execution of low demanding tasks (i.e. 2 and 3 moves), while the accuracy level between the two groups did not significantly differ. OCD patients required longer initial thinking time also during high demanding tasks (i.e., 4 and 5 moves), but in this case their accuracy was significantly worse than HCs' one. We did not find any association between impulsivity and PAs. Our results supported the hypothesis that OCD patients were not able to retain in memory the planned sequence and they had to reschedule their movements during the execution. Thus, future studies should deepen the interrelation between working memory and PA to better understand the influence between these two cognitive functions and their interaction with clinical variables in OCD patients.

2 Article Evaluating effect of symptoms heterogeneity on decision-making ability in obsessive-compulsive disorder. 2015

Martoni, Riccardo Maria / Brombin, Chiara / Nonis, Alessandro / Salgari, Giulia Carlotta / Buongiorno, Angela / Cavallini, Maria Cristina / Galimberti, Elisa / Bellodi, Laura. ·Department of Clinical Neurosciences, San Raffaele Scientific Institute, Milan, Italy. · Decision Theory in Neuroscience, Vita-Salute San Raffaele University, Milan, Italy. · Faculty of Psychology, Vita-Salute San Raffaele University, Milan, Italy. · CUSSB, University Center for Statistics in the Biomedical Sciences, Vita-Salute San Raffaele University, Milan, Italy. ·Psychiatry Clin Neurosci · Pubmed #25522816.

ABSTRACT: AIMS: Despite having a univocal definition, obsessive-compulsive disorder (OCD) shows a remarkably phenotypic heterogeneity. The published reports show impaired decision-making in OCD patients, using tasks such as the Iowa Gambling Task (IGT). We wanted to verify the hypothesis of an IGT worse performance in a large sample of OCD patients and healthy control (HC) subjects and to examine the relation between neuropsychological performance in IGT and the OCD symptoms heterogeneity. METHODS: Binary data from the Yale-Brown Obsessive Compulsive Scale collected on a large sample of OCD patients were analyzed using a multidimensional item response theory model to explore the underlying structure of data, thus revealing latent factors. Factor scores were categorized into quartiles. Then, for each factor, we identified patients respectively with the highest versus lowest score. We evaluated whether symptom dimensions affect the probability of a correct answer over time generalized, during IGT performance, fitting a generalized linear mixed model. RESULTS: We found a general deficit in ambiguous decision-making in OCD compared to HC. Moreover, our findings suggested that OCD symptoms heterogeneity affects decision-making learning abilities during IGT. In fact, while 'Symmetry' and 'Washing' patients showed a learning curve during the task, other subgroups did not. CONCLUSIONS: Our study confirmed previous findings suggesting that OCD is characterized by a deficit in decision-making under uncertainty. Moreover, our study gave evidence about biological specificity for each symptom dimension in OCD. Data were discussed in the context of the somatic marker hypothesis, which was hypothesized to be reduced in OCD patients.

3 Article 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 / Fagerness, Jesen A / Osiecki, Lisa / Gallagher, Patience / Gerber, Gloria / Haddad, Stephen / Illmann, Cornelia / McGrath, Lauren M / Mayerfeld, Catherine / Arepalli, Sampath / Barlassina, Cristina / Barr, Cathy L / Bellodi, Laura / Benarroch, Fortu / Berrió, 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, Daniele / 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 / Grünblatt, 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 / Mesa Restrepo, Sandra C / 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, Carlos N / Piacentini, John / Pittenger, Christopher / Pollak, Yehuda / Rauch, Scott L / Renner, Tobias / Reus, Victor I / Richter, Margaret A / Riddle, Mark A / Robertson, Mary M / Romero, Roxana / Rosário, Maria C / Rosenberg, David / Ruhrmann, Stephan / Sabatti, Chiara / 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 / Tischfield, Jay A / Turiel, Maurizio / Valencia Duarte, Ana V / Vallada, Homero / Veenstra-VanderWeele, Jeremy / Walitza, Susanne / Wang, Ying / Weale, Mike / Weiss, Robert / Wendland, Jens R / 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 / Oostra, Ben A / Nestadt, Gerald / Rouleau, Guy A / Purcell, Shaun / Jenike, Michael A / Heutink, Peter / Hanna, Gregory L / Conti, David V / Arnold, Paul D / Freimer, Nelson B / Stewart, S Evelyn / Knowles, James A / Cox, Nancy J / Pauls, David L. ·From the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston; the Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Mass.; the Department of Psychiatry, University of California, San Francisco; the Department of Neurology, Massachusetts General Hospital, Boston; the Division of Cognitive and Behavioral Neurology, Brigham and Women's Hospital, Boston; the Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston; Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago; the Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam; the Department of Preventive Medicine, Division of Biostatistics, Keck School of Medicine, University of Southern California, Los Angeles; the Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Md.; the Genomic and Bioinformatic Unit, Filarete Foundation, Milan, Italy; the Department of Health Sciences, Graduate School of Nephrology, University of Milan, Milan; the Toronto Western Research Institute, University Health Network, Toronto; Hospital for Sick Children, Toronto; Università Vita-Salute San Raffaele, Milan; the Herman Dana Division of Child and Adolescent Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem; Universidad de Antioquia, Universidad Pontificia Bolivariana, Medellín, Colombia; the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore; the Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City; the Child Study Center and the Department of Psychiatry, Yale University School of Medicine, New Haven, Conn.; the Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; North Shore-Long Island Jewish Medical Center and North Shore-Lo ·Am J Psychiatry · Pubmed #25158072.

ABSTRACT: 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=2×10(-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 Tourette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.

4 Article 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 / Rosário, 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 / Grünblatt, 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 / Tischfield, Jay A / Vallada, Homero / Veenstra-VanderWeele, Jeremy / Walitza, Susanne / Wang, Ying / Wendland, 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. ·Massachusetts General Hospital, Boston; American University, Washington, DC; Harvard-MIT Broad Institute, Boston. · Massachusetts General Hospital, Boston; Harvard-MIT Broad Institute, Boston. · University of Toronto and the Hospital for Sick Children, Toronto. · University of Chicago. · University of São Paulo Medical School. · Massachusetts General Hospital, Boston. · Harvard-MIT Broad Institute, Boston. · University of Toronto and the Hospital for Sick Children, Toronto; Toronto Western Research Institute, University Health Network, Toronto. · Università Vita-Salute San Raffaele, Milan. · Hadassah-Hebrew University Medical Center, Jerusalem. · Johns Hopkins University School of Medicine, Baltimore. · University of Iowa College of Medicine, Iowa City. · Yale University School of Medicine, New Haven, CT. · North Shore-Long Island Jewish Medical Center, New Hyde Park, NY; New York University Medical Center, New York. · North Shore-Long Island Jewish Medical Center, New Hyde Park, NY; Hofstra University School of Medicine, Hempstead, NY. · Instituto Nacional de Psiquiatría Ramon de la Fuente Muñiz, Mexico. · Utrecht University and VU Medical Center, Amsterdam. · Ospedale San Raffaele, Milan. · University of Montreal. · Robert Debre University Hospital, Paris and the French National Science Foundation, Creteil, France; Institut Pasteur, Paris. · Netherlands Institute for Neuroscience, Amsterdam; Academic Medical Center, Amsterdam. · Academic Medical Center, Amsterdam. · Federal University of São Paulo. · University of New South Wales, Australia. · University of Munich. · Hospital Nacional de Niños, San Jose, Costa Rica; Clinica Herrera Amighetti, Avenida Escazú, San José, Costa Rica. · University Medicine Greifswald, Greifswald, Germany. · Brown Medical School, Providence, RI. · Shaare Zedek Medical Center, Jerusalem. · University of Zurich. · Rutgers University, Piscataway Township, NJ. · University of Stellenbosch, South Africa. · Hospital Nacional de Niños, San Jose, Costa Rica. · Baylor College of Medicine, Houston. · Centre for Addiction and Mental Health, Toronto. · Atlantic Neuroscience Institute, Summit, NJ. · Carracci Medical Group, Mexico City. · Robert Debre University Hospital, Paris and the French National Science Foundation, Creteil, France; Institut Mondor de Recherche Biomédicale, Créteil, France. · University of Bonn, Germany. · University of California at San Francisco School of Medicine. · Cold Spring Harbor Laboratory, Cold Spring Harbor, NY. · University of California, Irvine. · University of California, Los Angeles (UCLA) School of Medicine. · University of Utah, Salt Lake City. · National Institute of Mental Health (NIMH) Intramural Research Program, Bethesda, MD. · Medical City Dallas Hospital. · Zilkha Neurogenetic Institute, Los Angeles. · University of Toronto and the Hospital for Sick Children, Toronto; Sunnybrook Health Sciences Centre, Toronto. · University College London. · Wayne State University and Detroit Medical Center, Detroit. · Montreal Neurological Institute. · University of Cologne, Germany. · Federal University of São Paulo; Universidade Federal da Bahia, Salvador, Bahia, Brazil. · VU Amsterdam and Erasmus University Medical Centre, Rotterdam; VU University Amsterdam; VU Medical Center, Amsterdam. · University of Cape Town, South Africa. · Vanderbilt University, Nashville, TN. · University of Zurich; University of Würzburg. · Erasmus Medical Center Rotterdam, the Netherlands. · German Center for Neurodegenerative Diseases, Bonn and VU Medical Center Amsterdam. · University of California, Los Angeles (UCLA) School of Medicine; Semel Institute for Neuroscience and Human Behavior, UCLA. · VU Amsterdam and Erasmus University Medical Centre, Rotterdam. · University of Michigan, Ann Arbor, MI. · Massachusetts General Hospital, Boston; University of British Columbia, Vancouver. · University of Illinois at Chicago. · Massachusetts General Hospital, Boston; Brigham and Womens Hospital, Boston; Harvard-MIT Broad Institute, Boston. Electronic address: jscharf@partners.org. ·J Am Acad Child Adolesc Psychiatry · Pubmed #25062598.

ABSTRACT: 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.

5 Article Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture. 2013

Davis, Lea K / Yu, Dongmei / Keenan, Clare L / Gamazon, Eric R / Konkashbaev, Anuar I / Derks, Eske M / Neale, Benjamin M / Yang, Jian / Lee, S Hong / Evans, Patrick / Barr, Cathy L / Bellodi, Laura / Benarroch, Fortu / Berrio, Gabriel Bedoya / Bienvenu, Oscar J / Bloch, Michael H / Blom, Rianne M / Bruun, Ruth D / Budman, Cathy L / Camarena, Beatriz / Campbell, Desmond / Cappi, Carolina / Cardona Silgado, Julio C / Cath, Danielle C / Cavallini, Maria C / Chavira, Denise A / Chouinard, Sylvain / Conti, David V / Cook, Edwin H / Coric, Vladimir / Cullen, Bernadette A / Deforce, Dieter / Delorme, Richard / Dion, Yves / Edlund, Christopher K / Egberts, Karin / Falkai, Peter / Fernandez, Thomas V / Gallagher, Patience J / Garrido, Helena / Geller, Daniel / Girard, Simon L / Grabe, Hans J / Grados, Marco A / Greenberg, Benjamin D / Gross-Tsur, Varda / Haddad, Stephen / Heiman, Gary A / Hemmings, Sian M J / Hounie, Ana G / Illmann, Cornelia / Jankovic, Joseph / Jenike, Michael A / Kennedy, James L / King, Robert A / Kremeyer, Barbara / Kurlan, Roger / Lanzagorta, Nuria / Leboyer, Marion / Leckman, James F / Lennertz, Leonhard / Liu, Chunyu / Lochner, Christine / Lowe, Thomas L / Macciardi, Fabio / McCracken, James T / McGrath, Lauren M / Mesa Restrepo, Sandra C / Moessner, Rainald / Morgan, Jubel / Muller, Heike / Murphy, Dennis L / Naarden, Allan L / Ochoa, William Cornejo / Ophoff, Roel A / Osiecki, Lisa / Pakstis, Andrew J / Pato, Michele T / Pato, Carlos N / Piacentini, John / Pittenger, Christopher / Pollak, Yehuda / Rauch, Scott L / Renner, Tobias J / Reus, Victor I / Richter, Margaret A / Riddle, Mark A / Robertson, Mary M / Romero, Roxana / Rosàrio, Maria C / Rosenberg, David / Rouleau, Guy A / Ruhrmann, Stephan / Ruiz-Linares, Andres / Sampaio, Aline S / Samuels, Jack / Sandor, Paul / Sheppard, Brooke / Singer, Harvey S / Smit, Jan H / Stein, Dan J / Strengman, E / Tischfield, Jay A / Valencia Duarte, Ana V / Vallada, Homero / Van Nieuwerburgh, Filip / Veenstra-Vanderweele, Jeremy / Walitza, Susanne / Wang, Ying / Wendland, Jens R / Westenberg, Herman G M / Shugart, Yin Yao / Miguel, Euripedes C / McMahon, William / Wagner, Michael / Nicolini, Humberto / Posthuma, Danielle / Hanna, Gregory L / Heutink, Peter / Denys, Damiaan / Arnold, Paul D / Oostra, Ben A / Nestadt, Gerald / Freimer, Nelson B / Pauls, David L / Wray, Naomi R / Stewart, S Evelyn / Mathews, Carol A / Knowles, James A / Cox, Nancy J / Scharf, Jeremiah M. ·Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, Illinois, United States of America. ·PLoS Genet · Pubmed #24204291.

ABSTRACT: The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.

6 Article 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 / Davis, L K / 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, 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 / Umaña, P / Murphy, D L / Wendland, J R / Veenstra-VanderWeele, J / Denys, D / Blom, R / Deforce, D / Van Nieuwerburgh, F / Westenberg, H G M / Walitza, S / Egberts, K / Renner, T / Miguel, E C / Cappi, C / Hounie, A G / Conceição do Rosário, M / 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 / Anonymous1030734 / Hardy, J / Anonymous1040734 / 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. ·Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Harvard Medical School, Boston, MA 02114, USA. sevelynstewart@gmail.com ·Mol Psychiatry · Pubmed #22889921.

ABSTRACT: 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 × 10(-6) and P=3.44 × 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 × 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 × 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.

7 Article The somatic marker affecting decisional processes in obsessive-compulsive disorder. 2012

Cavedini, Paolo / Zorzi, Claudia / Baraldi, Clementina / Patrini, Sara / Salomoni, Giuliana / Bellodi, Laura / Freire, Rafael C / Perna, Giampaolo. ·Department of Clinical Neurosciences, Villa San Benedetto Hospital, Hermanas Hospitalarias, Albese con Cassano, Italy. p.cavedini@paolocavedini.com ·Cogn Neuropsychiatry · Pubmed #21991936.

ABSTRACT: INTRODUCTION: Patients with obsessive-compulsive disorder (OCD) demonstrate impairment in decisional processes in which both cognition and emotion play a crucial role. METHODS: We investigated the connection between decision-making performances and choice-related skin conductance responses (SCRs), to identify a somatic marker impairment affecting decisional processes in these patients. We explored SCRs during the Iowa Gambling Task in 20 OCD and 18 control, measuring anticipatory and posticipatory psychophysiological reactions according to card choices and to the outcomes of each selection. RESULTS: Most patients exhibited weaker SCRs compared to HC, although there weren't substantial differences in magnitude between the two groups. In contrast with HC, patients with OCD showed no significant differences of SCRs activation according to card selections; they chose cards from neither favourable nor unfavourable decks. CONCLUSIONS: The main finding of the study were the evidence of a dysfunctional biological marker in OCD subjects, affecting decision-making process. Dysfunctional patterns of SCRs could partially explain OCDs' impairment in this ability. Decision-making deficits in OCDs could be influenced in part by the lack of somatic differences in discriminating between advantageous and disadvantageous behaviour. These findings could lead to a more complete understanding of OCD.

8 Article Executive dysfunctions in obsessive-compulsive patients and unaffected relatives: searching for a new intermediate phenotype. 2010

Cavedini, Paolo / Zorzi, Claudia / Piccinni, Monica / Cavallini, Maria Cristina / Bellodi, Laura. ·Department of Clinical Neurosciences, Villa San Benedetto Hospital, Hermanas Hospitalarias, Albese con Cassano, Italy. p.cavedini@paolocavedini.com ·Biol Psychiatry · Pubmed #20381015.

ABSTRACT: BACKGROUND: Evidence in literature suggests that neurocognitive deficits may represent suitable intermediate-phenotype candidates for the dissection of obsessive-compulsive disorder (OCD) genetic heterogeneity. The aim of this study was to search for possible OCD neurocognitive endophenotypes by assessing decision-making, planning, and mental flexibility profiles in OCD probands, healthy control subjects (HC), and their respective relatives. METHODS: The sample consisted of 35 pairs of OCD probands without other Axis I comorbidities and unaffected first-degree relatives and 31 pairs of HC subjects without a known family history of OCD and their relatives. Neuropsychological assessment was performed using the Iowa Gambling Task (IGT), the Tower of Hanoi (ToH), and the Wisconsin Card Sorting Test (WCST). RESULTS: Obsessive-compulsive disorder patients showed impairments in decision making, planning, and mental flexibility, given that OCD probands performed significantly poorer than HC probands at the IGT, the ToH, and the WCST. Obsessive-compulsive disorder relatives performed poorer at these tests than HC probands and relatives. Symptom severity was found to have no influence on neurocognitive performance. Analysis of proband/relative concordance in task performance was performed for each task. A significant overall difference was found when comparing the percentages of the different concordance profiles of our OCD and HC samples with regard to IGT and ToH performance. No significant difference was found in the WCST. CONCLUSIONS: Executive dysfunctions may qualify as a suitable endophenotype candidate for OCD. Concordance rates in neuropsychological task performance suggest that decision-making and planning deficits aggregate in these families and therefore might be a heritable component of OCD.

9 Article Disorganization of anatomical connectivity in obsessive compulsive disorder: a multi-parameter diffusion tensor imaging study in a subpopulation of patients. 2010

Garibotto, V / Scifo, P / Gorini, A / Alonso, Clarke R / Brambati, S / Bellodi, L / Perani, D. ·Vita-Salute San Raffaele University, Milan, Italy. ·Neurobiol Dis · Pubmed #19913616.

ABSTRACT: Obsessive-compulsive disorder (OCD) is thought to involve large-scale brain systems but the anatomical connectivity via association fibers has not been specifically investigated yet. We evaluated organization and directionality of the major fiber bundles in a subpopulation of OCD, including washers and checkers who presented decision making deficits, by measuring MRI parameters related to water self-diffusion (Fractional Anisotropy, FA) and fiber directionality (Principal Diffusion Direction, PDD) in 15 OCD and 16 control subjects. OCD patients showed significantly lower FA and altered PDD along the corpus callosum, cingulum, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus bilaterally. The track-based analysis of the inferior fronto-occipital fasciculus confirmed a significant bilateral FA reduction. Lower FA values in the inferior fronto-occipital fasciculus, superior longitudinal fasciculus and corpus callosum correlated with symptom severity and neuropsychological performance. This multi-parameter MRI study revealed specific white matter abnormalities in OCD suggesting tract disorganization as main feature, reflected by local changes in fiber directionality. This altered anatomical connectivity might play a specific role in OCD pathophysiology.

10 Article Artificial neural network model for the prediction of obsessive-compulsive disorder treatment response. 2009

Salomoni, Giuliana / Grassi, Massimiliano / Mosini, Paola / Riva, Patrizia / Cavedini, Paolo / Bellodi, Laura. ·Department of Clinical Neuroscience, School of Pyschology, San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy. ·J Clin Psychopharmacol · Pubmed #19593173.

ABSTRACT: Several patients with obsessive-compulsive disorder (OCD) who are refractory to adequate treatment with first-line treatments are considered treatment-resistant. Further surveys were to be implemented to explore the outcome predictors of the antiobsessional response. Such study was aimed at building a model suitable to predict the final outcome of a mixed OCD pharmacologic and nonpharmacologic treatment approaches. We studied 130 subjects with OCD who underwent pharmacologic (with selective serotonin reuptake inhibitors alone or with selective serotonin reuptake inhibitors and risperidone at low dosage) and/or behavioral therapy (using exposure and response prevention techniques). The following variables were used as predictors: symptoms dimension, as resulting from the Yale-Brown Obsessive-Compulsive Scale items factor analysis; neuropsychologic performances; and epidemiologic variables. The treatment response arising from 3 to 6 months of therapy was used as dependent variable. A conventional logistic regression was used to define a previsional model of treatment response and multilayer perceptrons and to supervise an artificial neural network technique. The 46.9% of the sample resulted to be refractory to treatment. Results obtained with the logistic regression model showed that the only predictors of treatment outcome are hoarding symptoms, repeating rituals, and counting compulsions. Furthermore, using all the variables considered in the models, multilayer perceptrons showed highly better predictive performance as compared with the logistic regression models (93.3% vs 61.5%, respectively, of correct classification of cases). Complex interactions between different clinical and neuropsychologic variables are involved in defining OCD treatment response profile, and nonlinear and interactive modeling strategies, that is, supervised artificial neural networks, seem to be more suitable to investigate this complexity than linear techniques.

11 Article In vivo PET study of 5HT(2A) serotonin and D(2) dopamine dysfunction in drug-naive obsessive-compulsive disorder. 2008

Perani, Daniela / Garibotto, Valentina / Gorini, Alessandra / Moresco, Rosa Maria / Henin, Marta / Panzacchi, Andrea / Matarrese, Mario / Carpinelli, Assunta / Bellodi, Laura / Fazio, Ferruccio. ·Vita-Salute San Raffaele University, Milan, Italy. ·Neuroimage · Pubmed #18511303.

ABSTRACT: There are several lines of evidence, the majority indirect, suggesting that changes in serotonergic or dopaminergic neurotransmission may contribute to the pathogenesis of obsessive-compulsive disorder (OCD). We evaluated the co-occurrence of serotonergic and dopaminergic dysfunctions in OCD subjects, all drug-naive, with no co-morbidity and homogeneous for symptoms. Each subject underwent two positron emission tomography (PET) scans to measure in vivo both serotonin (5-HT(2A)) and dopamine (D(2)) receptor distribution. For this, we used [11C]MDL and [11C]Raclopride, highly selective antagonists of 5-HT(2A) and D(2) receptors, respectively. The comparison with a control group was carried out using both voxel-wise (SPM2) and regions of interest (ROI) approaches. There was a significant reduction of 5-HT(2A) receptor availability in frontal polar, dorsolateral, and medial frontal cortex, as well as in parietal and temporal associative cortex of OCD patients. We also found a significant correlation between 5-HT(2A) receptor availability in orbitofrontal and dorsolateral frontal cortex and clinical severity, suggesting a specific role for serotonin in determining the OCD symptoms. There was also a significant reduction of [11C]Raclopride uptake in the whole striatum, particularly in the ventral portion, possibly reflecting endogenous dopaminergic hyperactivity. The co-existence of serotonergic and dopaminergic dysfunction in the same homogeneous group of drug-naive OCD patients provides in vivo evidence for the complex molecular mechanisms of OCD, and represents the basis for further studies on the effect of therapeutic agents with specific modulatory effects on these neurotransmission systems.