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2. A proof-of-concept study applying machine learning methods to putative risk factors for eating disorders: results from the multi-centre European project on healthy eating.

Author

Krug, I, Linardon, J, Greenwood, C, Youssef, G, Treasure, J, Fernandez-Aranda, F, Karwautz, A, Wagner, G, Collier, D, Anderluh, M, Tchanturia, K, Ricca, V, Sorbi, S, Nacmias, B, Bellodi, L, Fuller-Tyszkiewicz, M, Krug, I, Linardon, J, Greenwood, C, Youssef, G, Treasure, J, Fernandez-Aranda, F, Karwautz, A, Wagner, G, Collier, D, Anderluh, M, Tchanturia, K, Ricca, V, Sorbi, S, Nacmias, B, Bellodi, L, and Fuller-Tyszkiewicz, M

Abstract

BACKGROUND: Despite a wide range of proposed risk factors and theoretical models, prediction of eating disorder (ED) onset remains poor. This study undertook the first comparison of two machine learning (ML) approaches [penalised logistic regression (LASSO), and prediction rule ensembles (PREs)] to conventional logistic regression (LR) models to enhance prediction of ED onset and differential ED diagnoses from a range of putative risk factors. METHOD: Data were part of a European Project and comprised 1402 participants, 642 ED patients [52% with anorexia nervosa (AN) and 40% with bulimia nervosa (BN)] and 760 controls. The Cross-Cultural Risk Factor Questionnaire, which assesses retrospectively a range of sociocultural and psychological ED risk factors occurring before the age of 12 years (46 predictors in total), was used. RESULTS: All three statistical approaches had satisfactory model accuracy, with an average area under the curve (AUC) of 86% for predicting ED onset and 70% for predicting AN v. BN. Predictive performance was greatest for the two regression methods (LR and LASSO), although the PRE technique relied on fewer predictors with comparable accuracy. The individual risk factors differed depending on the outcome classification (EDs v. non-EDs and AN v. BN). CONCLUSIONS: Even though the conventional LR performed comparably to the ML approaches in terms of predictive accuracy, the ML methods produced more parsimonious predictive models. ML approaches offer a viable way to modify screening practices for ED risk that balance accuracy against participant burden.

Published
2023

3. A proof-of-concept study applying machine learning methods to putative risk factors for eating disorders: results from the multi-centre European project on healthy eating.

Author

Krug, I., Linardon, J., Greenwood, C., Youssef, G., Treasure, J., Fernandez-Aranda, F., Karwautz, A., Wagner, G., Collier, D., Anderluh, M., Tchanturia, K., Ricca, V., Sorbi, S., Nacmias, B., Bellodi, L., and Fuller-Tyszkiewicz, M.

Subjects
RESEARCH, MACHINE learning, DIFFERENTIAL diagnosis, RETROSPECTIVE studies, RISK assessment, BULIMIA, QUESTIONNAIRES, AGE factors in disease, DESCRIPTIVE statistics, RESEARCH funding, ANOREXIA nervosa, PREDICTION models, LOGISTIC regression analysis, EATING disorders
Abstract

Background: Despite a wide range of proposed risk factors and theoretical models, prediction of eating disorder (ED) onset remains poor. This study undertook the first comparison of two machine learning (ML) approaches [penalised logistic regression (LASSO), and prediction rule ensembles (PREs)] to conventional logistic regression (LR) models to enhance prediction of ED onset and differential ED diagnoses from a range of putative risk factors. Method: Data were part of a European Project and comprised 1402 participants, 642 ED patients [52% with anorexia nervosa (AN) and 40% with bulimia nervosa (BN)] and 760 controls. The Cross-Cultural Risk Factor Questionnaire, which assesses retrospectively a range of sociocultural and psychological ED risk factors occurring before the age of 12 years (46 predictors in total), was used. Results: All three statistical approaches had satisfactory model accuracy, with an average area under the curve (AUC) of 86% for predicting ED onset and 70% for predicting AN v. BN. Predictive performance was greatest for the two regression methods (LR and LASSO), although the PRE technique relied on fewer predictors with comparable accuracy. The individual risk factors differed depending on the outcome classification (EDs v. non-EDs and AN v. BN). Conclusions: Even though the conventional LR performed comparably to the ML approaches in terms of predictive accuracy, the ML methods produced more parsimonious predictive models. ML approaches offer a viable way to modify screening practices for ED risk that balance accuracy against participant burden. [ABSTRACT FROM AUTHOR]

Published
2023
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4. A proof-of-concept study applying machine learning methods to putative risk factors for eating disorders: results from the multi-centre European project on healthy eating

Author

Krug, I., primary, Linardon, J., additional, Greenwood, C., additional, Youssef, G., additional, Treasure, J., additional, Fernandez-Aranda, F., additional, Karwautz, A., additional, Wagner, G., additional, Collier, D., additional, Anderluh, M., additional, Tchanturia, K., additional, Ricca, V., additional, Sorbi, S., additional, Nacmias, B., additional, Bellodi, L., additional, and Fuller-Tyszkiewicz, M., additional

Published
2021
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5. Genome-wide association study of obsessive-compulsive disorder

Author

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, 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, 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, and Pauls, D L

Published
2013
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7. Revealing the complex genetic architecture of obsessive-compulsive disorder using meta-analysis

Author

nternational Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC), OCD Collaborative Genetics Association Studies (OCGAS): Arnold PD, Askland KD, Barlassina C, Bellodi L, Bienvenu OJ, Black D, Bloch M, Brentani H, Burton CL, Camarena B, Cappi C, Cath D, Cavallini M, Conti D, Cook E, Coric V, Cullen BA, Cusi D, Davis LK, Delorme R, Denys D, Derks E, Eapen V, Edlund C, Erdman L, Falkai P, Figee M, Fyer AJ, Geller DA, Goes FS, Grabe H, Grados MA, Greenberg BD, Grünblatt E, Guo W, Hanna GL, Hemmings S, Hounie AG, Jenicke M, Keenan C, Kennedy J, Khramtsova EA, Konkashbaev A, Knowles JA, Krasnow J, Lange C, Lanzagorta N, Leboyer M, Lennertz L, Li B, Liang KY, Lochner C, Macciardi F, Maher B, Maier W, Marconi M, Mathews CA, Matthesien M, McCracken JT, McLaughlin NC, Miguel EC, Moessner R, Murphy DL, Neale B, Nestadt G, Nestadt P, Nicolini H, Nurmi E, Osiecki L, Pauls DL, Piacentini J, Posthuma D, Pulver AE, Qin HD, Rasmussen SA, Rauch S, Richter MA, Riddle MA, Ripke S, Ruhrmann S, Sampaio AS, Samuels JF, Scharf JM, Shugart YY, Smit J, Stein D, Stewart SE, Turiel M, Vallada H, Veenstra-VanderWeele J, Wagner M, Walitza S, Wang Y, Wendland J, Vulink N, Yu D, Zai G., Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Psychiatry, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Reproduction & Development (AR&D), Human genetics, ANS - Compulsivity, Impulsivity & Attention, Adult Psychiatry, APH - Mental Health, Arnold, Paul D, Askland, Kathleen D, Barlassina, Cristina, Bellodi, Laura, Bienvenu, O. J, Black, Donald, Bloch, Michael, Brentani, Helena, Burton, Christie L, Camarena, Beatriz, Cappi, Carolina, Cath, Danielle, Cavallini, Maria, Conti, David, Cook, Edwin, Coric, Vladimir, Cullen, Bernadette A, Cusi, Danielle, Davis, Lea K, Delorme, Richard, Denys, Damiaan, Derks, Eske, Eapen, Valsamma, Edlund, Christopher, Erdman, Lauren, Falkai, Peter, Figee, Martijn, Fyer, Abigail J, Geller, Daniel A, Goes, Fernando S, Grabe, Han, Grados, Marcos A, Greenberg, Benjamin D, Grünblatt, Edna, Guo, Wei, Hanna, Gregory L, Hemmings, Sian, Hounie, Ana G, Jenicke, Michael, Keenan, Clare, Kennedy, Jame, Khramtsova, Ekaterina A, Konkashbaev, Anuar, Knowles, James A, Krasnow, Janice, Lange, Cristophe, Lanzagorta, Nuria, Leboyer, Marion, Lennertz, Leonhard, Li, Bingbin, Liang, K. y, Lochner, Christine, Macciardi, Fabio, Maher, Brion, Maier, Wolfgang, Marconi, Maurizio, Mathews, Carol A, Matthesien, Manuel, Mccracken, James T, Mclaughlin, Nicole C, Miguel, Euripedes C, Moessner, Rainald, Murphy, Dennis L, Neale, Benjamin, Nestadt, Gerald, Nestadt, Paul, Nicolini, Humberto, Nurmi, Ericka, Osiecki, Lisa, Pauls, David L, Piacentini, John, Posthuma, Danielle, Pulver, Ann E, Qin, H. d, Rasmussen, Steven A, Rauch, Scott, Richter, Margaret A, Riddle, Mark A, Ripke, Stephan, Ruhrmann, Stephan, Sampaio, Aline S, Samuels, Jack F, Scharf, Jeremiah M, Shugart, Yin Yao, Smit, Jan, Stein, Daniel, Stewart, S. Evelyn, Turiel, Maurizio, Vallada, Homero, Veenstra vanderweele, Jeremy, Wagner, Michael, Walitza, Susanne, Wang, Y, Wendland, Jen, Vulink, Nienke, Yu, Dongmei, Zai, Gwyneth, and Netherlands Institute for Neuroscience (NIN)

Subjects
0301 basic medicine, Genetics, TRANSTORNO OBSESSIVO-COMPULSIVO, Single-nucleotide polymorphism, Odds ratio, Biology, Heritability, Confidence interval, Genetic architecture, Minor allele frequency, 03 medical and health sciences, Cellular and Molecular Neuroscience, Psychiatry and Mental health, 030104 developmental biology, 0302 clinical medicine, Journal Article, SNP, SDG 2 - Zero Hunger, Molecular Biology, 030217 neurology & neurosurgery, Genetic association
Abstract

Two obsessive-compulsive disorder (OCD) genome-wide association studies (GWASs) have been published by independent OCD consortia, the International Obsessive-Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and the OCD Collaborative Genetics Association Study (OCGAS), but many of the top-ranked signals were supported in only one study. We therefore conducted a meta-analysis from the two consortia, investigating a total of 2688 individuals of European ancestry with OCD and 7037 genomically matched controls. No single-nucleotide polymorphisms (SNPs) reached genome-wide significance. However, in comparison with the two individual GWASs, the distribution of P-values shifted toward significance. The top haplotypic blocks were tagged with rs4733767 (P=7.1 × 10(-7); odds ratio (OR)=1.21; confidence interval (CI): 1.12-1.31, CASC8/CASC11), rs1030757 (P=1.1 × 10(-6); OR=1.18; CI: 1.10-1.26, GRID2) and rs12504244 (P=1.6 × 10(-6); OR=1.18; CI: 1.11-1.27, KIT). Variants located in or near the genes ASB13, RSPO4, DLGAP1, PTPRD, GRIK2, FAIM2 and CDH20, identified in linkage peaks and the original GWASs, were among the top signals. Polygenic risk scores for each individual study predicted case-control status in the other by explaining 0.9% (P=0.003) and 0.3% (P=0.0009) of the phenotypic variance in OCGAS and the European IOCDF-GC target samples, respectively. The common SNP heritability in the combined OCGAS and IOCDF-GC sample was estimated to be 0.28 (s.e.=0.04). Strikingly, ∼65% of the SNP-based heritability in the OCGAS sample was accounted for by SNPs with minor allele frequencies of ⩾40%. This joint analysis constituting the largest single OCD genome-wide study to date represents a major integrative step in elucidating the genetic causes of OCD.Molecular Psychiatry advance online publication, 1 August 2017; doi:10.1038/mp.2017.154.

Published
2018

17. Erratum: Genome-wide association study of obsessive-compulsive disorder

Author

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, Umaña, P, Murphy, D L, Wendland, J R, Veenstra-Vander Weele, 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, 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, and Pauls, D L

Published
2013
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20. Manifesto for a European research network into obsessive-compulsive and related disorders

Author

Alonso, P, Andreewitch, S, Baldwin, D, Bellodi, L, Bersani, Giuseppe, Cath, D, Chamberlain, S, Clark, L, Craig, K, Denys, D, Dell'Osso, B, Eilam, D, Fineberg, N, Goudriaan Anna, E, Grünblatt, E, Hermesh, H, Heyman, I, Hollander, E, Hranov, G, Hranov, L, Ivarsson, T, Joel, D, Matthews, K, Lochner, C, Marazziti, D, Mataix Cols, D, Menchon, J, Noldus, L, Pallanti, S, Robbins, T, Romanos, M, Renner, T, Rück, C, Sahakian, B, Stein, D, van den Brink, W, van den Heuvel, O, van der Wee, N, Veltman, D, Walitza, S, Zohar, J., Amsterdam Neuroscience, Adult Psychiatry, Other departments, Fineberg, Na, Baldwin, D, Menchon, Jm, Denys, D, Grünblatt, E, Pallanti, S, Stein, Dj, Zohar, J, Bellodi, Laura, Anatomy and neurosciences, Psychiatry, and NCA - Neurobiology of mental health

Subjects
Pharmacology, Manifesto, Obsessive-Compulsive Disorder, medicine.medical_specialty, Biomedical Research, International Cooperation, Mental Disorders, medicine.disease, Neuropsychopharmacology, Psychiatry and Mental health, Neurology, Body dysmorphic disorder, medicine, Humans, Hoarding disorder, Anxiety, Autism, Pharmacology (medical), Spectrum disorder, Neurology (clinical), medicine.symptom, Psychology, Psychiatry, Socioeconomic status, Biological Psychiatry
Abstract

Obsessive-compulsive and related disorders (O-CRDs) are highly disabling psychiatric illnesses of early-onset. They are responsible for considerable morbidity and socioeconomic burden. Existing treatments are usually only partially successful and there is an urgent need to understand the aetiological factors and neurobiological bases of the disorders in order to develop new and more effective strategies for prevention, early detection and effective treatment. Emerging data from the neurosciences supports the reconceptualisation of obsessive-compulsive disorder as a spectrum disorder, related to but different from the anxiety disorders and closely aligned with other less well understood psychiatric disorders characterised by compulsive acts such as body dysmorphic disorder, trichotillomania, skin-picking disorder, hoarding disorder; and possibly extending to tic disorders and other neurodevelopmental disorders such as autism. A new, O-CRDs research network, supported by the Networks Initiative of the European College of Neuropsychopharmacology and comprising leading figures in preclinical and clinical research, has been established. It aims to provide a European perspective on the current debate around internationally-accepted diagnostic criteria and treatment strategies for O-CRDs. Its objectives include; (1) identifying the key outstanding research questions that depend upon cross-centre collaborative investigation, (2) setting a research agenda that is likely to produce an impact on health-outcomes, and (3) strengthening existing projects and collaborative enterprises with these objectives in mind. This paper reviews some of these critical research priorities. By establishing shared multinational databases, collaborative research networks, multicentre studies and joint publications, it is hoped that progress will be achieved.

Published
2013

24. Novel Antidepressants and Panic Disorder: Evidence beyond Current Guidelines

Author

Serretti, A, Chiesa, A, Calati, R, Perna, G, Bellodi, L, De Ronchi, D, Serretti A, Chiesa A, Calati R, Perna G, Bellodi L, De Ronchi D, Serretti, A, Chiesa, A, Calati, R, Perna, G, Bellodi, L, De Ronchi, D, Serretti A, Chiesa A, Calati R, Perna G, Bellodi L, and De Ronchi D

Abstract

Aim: The aim of the present review is to summarize available evidence about the efficacy and side effects of novel antidepressants for the treatment of panic disorder. Methods: A literature search was undertaken using MEDLINE, ISI web of knowledge and references of retrieved articles. The search included articles published in English up to September 2009. Both controlled and uncontrolled trials were included. The quality of the reviewed articles was also assessed. Results: Fourteen mainly poor-quality studies were included. Mirtazapine showed some efficacy in reducing the number and the severity of panic symptoms in many uncontrolled studies and was comparable to selective serotonin reputake inhibitors (SSRIs) in direct-comparison studies. Reboxetine was significantly more efficacious than placebo but less effective than SSRIs. Further uncontrolled studies suggested preliminary evidence for the use of milnacipran and duloxetine as well. All drugs were usually well tolerated. Discussion: Current studies do not yet provide convincing evidence supporting the efficacy of mirtazapine, reboxetine, milnacipran and duloxetine for the treatment of panic disorder patients. However, on account of positive preliminary results, further research is warranted. © 2010 S. Karger AG, Basel.

Published
2011

25. Common genetic, clinical; demographic and psychosocial predictors of response to pharmacotherapy in mood and anxiety disorders

Author

Serretti, A, Chiesa, A, Calati, R, Perna, G, Bellodi, L, De Ronchi, D, Serretti A, Chiesa A, Calati R, Perna G, Bellodi L, De Ronchi D, Serretti, A, Chiesa, A, Calati, R, Perna, G, Bellodi, L, De Ronchi, D, Serretti A, Chiesa A, Calati R, Perna G, Bellodi L, and De Ronchi D

Abstract

The aim of this study is to summarize available knowledge about common genetic, clinical, demographic and psychosocial predictors of response to pharmacotherapy in mood and anxiety disorders. A literature search was carried out by using MEDLINE and references of selected articles. The search included articles published up to March 2008. The main genetic finding concerns the serotonin transporter gene promoter polymorphisms, the long variant of which seems to be related to a positive response to therapy in mood disorders and could also have a role in the treatment of anxiety disorders. Among other predictors, the main factors common to both classes of disorder are comorbid axis II disorders and early onset of illness, which are related to a worse response to therapy and concomitant good physical conditions, absence of earlier treatments, early administration and response to therapies, and higher self-directedness, which is related to a better outcome. Many common predictors have been identified and these seem to be related to features covering the totality of patients that go beyond specific characteristics of single disorders. Possible limitations and suggestions for future research based on a more integrated vision of human complexity are discussed. Int Clin Psychopharmacol 24:1-18 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Published
2009

28. Disturbo ossessivo-compulsivo

Author

Albert, Umberto, Bellodi, L., C. Altamura F. Bogetto M. Casacchia G. Muscettola M. Maj, U. Albert, L. Bellodi, Albert, U., and Bellodi, L.

Subjects
no
Published
2012

29. NEUROCOGNITIVE FUNCTIONING IN UNTREATED PATIENTS WITH BULIMIA NERVOSA: NEUROENDOCRINE, PERSONALITY AND CLINICAL CORRELATES

Author

Bucci, P., Galderisi, S., Mucci, A., Bellodi, L., Cassano, G. B., Santonastaso, P., Erzegovesi, S., Favaro, A., Mauri, M., Tenconi, E., Monteleone, Palmiero, Maj, M., Bucci, P., Galderisi, S., Mucci, A., Bellodi, Laura, Cassano, G. B., Santonastaso, P., Erzegovesi, S., Favaro, A., Mauri, M., Tenconi, E., Monteleone, P., Maj, M., Bucci, Paola, Galderisi, Silvana, Mucci, Armida, Bellodi, L, Cassano G., B, Santonastaso, P, Erzegovesi, S, Favaro, A, Mauri, M, Tenconi, E, Monteleone, P, and Maj, Mario

Published
2010

32. In vivo PET study of 5HT2A serotonin and D2 dopamine dysfunction in drug-naive obsessive-compulsive disorder

Author

Perani D. 1, 2, 3, Garibotto V. 1, Gorini A. 1, Moresco R.M. 2, 4, 5, Henin M. 3, Panzacchi A. 2, Matarrese M. 4, Carpinelli A. 4, Bellodi L. 1, Fazio F. 2, Perani, D, Garibotto, V, Gorini, A, Moresco, R, Henin, M, Panzacchi, A, Matarrese, M, Carpinelli, A, Bellodi, L, Fazio, F, Perani, DANIELA FELICITA L., Moresco, Rm, Bellodi, Laura, and Fazio, F.

Subjects
Adult, Serotonin, Obsessive-Compulsive Disorder, Cognitive Neuroscience, Dopamine, Striatum, Serotonergic, behavioral disciplines and activities, Young Adult, mental disorders, medicine, Serotonin 5-HT2 Receptor Antagonists, Humans, Receptor, Serotonin, 5-HT2A, Tissue Distribution, 5HT2A, D2, 5-HT receptor, Raclopride, Receptors, Dopamine D2, OCD, dopamine, serotonin, PET, Dopaminergic, Brain, Middle Aged, Dopamine D2 Receptor Antagonists, PET, Neurology, Positron-Emission Tomography, Female, Radiopharmaceuticals, Psychology, Neuroscience, medicine.drug
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-HT2A) and dopamine (D-2) receptor distribution. For this, we used [C-11]MDL and [C-11] Raclopride, highly selective antagonists of 5-HT2A 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-HT2A 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-HT2A receptor availability in orbito-frontal 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 [C-11]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. (c) 2008 Elsevier Inc. All rights reserved.

Published
2008

34. Fat mass and obesity-associated gene (FTO) in eating disorders : Evidence for association of the rs9939609 obesity risk allele with Bulimia nervosa and anorexia nervosa

Author

Müller, T.D., Greene, B.H., Bellodi, L., Cavallini, M.C., Cellini, E., di Bella, D., Ehrlich, S., Erzegovesi, S., Estivill, X., Fernández-Aranda, F., Fichter, M., Fleischhaker, C., Scherag, S., Gratacòs, M., Grallert, H., Herpertz-Dahlmann, B., Herzog, W., Illig, T., Lehmkuhl, U., Nacmias, B., Ribasés, M., Ricca, V., Schäfer, H., Scherag, A., Sorbi, S., Wichmann, H.-E., Hebebrand, J., Hinney, A., Universitat de Barcelona, Müller, Td, Greene, Bh, Bellodi, Laura, Cavallini, Mc, Cellini, E, Di Bella, D, Ehrlich, S, Erzegovesi, S, Estivill, X, Fernández Aranda, F, Fichter, M, Fleischhaker, C, Scherag, S, Gratacòs, M, Grallert, H, Herpertz Dahlmann, B, Herzog, W, Illig, T, Lehmkuhl, U, Nacmias, B, Ribasés, M, Ricca, V, Schäfer, H, Scherag, A, Sorbi, S, Wichmann, He, Hebebrand, J, and Hinney, A.

Subjects
Adult, Male, Risk, Anorexia Nervosa, Adolescent, Genotype, Medizin, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Polymorphism, Single Nucleotide, Young Adult, 610 Medical sciences Medicine, Confidence Intervals, Odds Ratio, Humans, Obesity, Bulímia, Bulimia, Bulimia Nervosa, Child, Trastorns de la conducta alimentària, Alleles, Proteins, Anorèxia nerviosa, Fat Mass And Obesity-associated Gene, Fto, Eating Disorders, Association Study, Anorexia nervosa, Middle Aged, anorexia, Eating disorders, Obesitat, Female
Abstract

Objective: The common single nucleotide polymorphism (SNP) rs9939609 in the fat mass and obesity-associated gene (FTO) is associated with obesity. As genetic variants associated with weight regulation might also be implicated in the etiology of eating disorders, we evaluated whether SNP rs9939609 is associated with bulimia nervosa (BN) and anorexia nervosa (AN). Methods: Association of rs9939609 with BN and AN was assessed in 689 patients with AN, 477 patients with BN, 984 healthy non-population-based controls, and 3,951 population-based controls (KORA-S4). Based on the familial and premorbid occurrence of obesity in patients with BN, we hypothesized an association of the obesity risk A-allele with BN. Results: In accordance with our hypothesis, we observed evidence for association of the rs9939609 A-allele with BN when compared to the non-population-based controls (unadjusted odds ratio (OR) = 1.142, one-sided 95% confidence interval (CI) 1.001-infinity; one-sided p = 0.049) and a trend in the population-based controls (OR = 1.124, one-sided 95% CI 0.932-infinity; one-sided p = 0.056). Interestingly, compared to both control groups, we further detected a nominal association of the rs9939609 A-allele to AN (OR = 1.181, 95% CI 1.027-1.359, two-sided p = 0.020 or OR = 1.673, 95% CI 1.101-2.541, two-sided p = 0.015,). Conclusion: Our data suggest that the obesity-predisposing FTO allele might be relevant in both AN and BN. Copyright (C) 2012 S. Karger GmbH, Freiburg

Published
2012

35. Memory Functioning in Obsessive-Compulsive Disorder

Author

Abbruzzese, M., Bellodi, L., Ferri, S., and silvio scarone

Subjects
Neuropsychology and Physiological Psychology, Neurology, mental disorders, Neurosciences. Biological psychiatry. Neuropsychiatry, Neurology (clinical), General Medicine, behavioral disciplines and activities, humanities, RC321-571
Abstract

A number of studies have reported neuropsychological deficits in obsessive-compulsive disorder (OCD). These have mainly implicated frontal or temporal dysfunction. In this study, we compared the performances of OCD patients and normal subjects using a factorial interpretation of the Wechsler Memory Scale. Our results do not demonstrate significant memory impairment in OCD patients but point to the possibility of frontal lobe dysfunction as a factor in the pathophysiology of OCD.

Published
1993

37. Copy number variation in obsessive-compulsive disorder and tourette syndrome: A cross-disorder study

Author

McGrath, L.M., Yu, D. (D.), Marshall, C.R. (Christian), Davis, L.K. (Lea), Thiruvahindrapuram, B. (Bhooma), Li, B. (Bingbin), Cappi, C. (Carolina), Gerber, G. (Gloria), Wolf, A. (Anneke) de, Schroeder, F.A. (Frederick), Osiecki, L. (Lisa), O'Dushlaine, C. (Colm), Kirby, A. (Andrew), Illmann, C. (Cornelia), Haddad, S. (Stephen), Gallagher, P. (Patience), Fagerness, J. (Jesen), Barr, C.L. (Cathy), Bellodi, L. (Laura), Benarroch, F. (Fortu), Bienvenu, O.J. (Oscar), Black, D.W. (Donald), Bloch, J. (Jocelyne), Bruun, R.D. (Ruth), Budman, C.L. (Cathy), Camarena, B. (Beatriz), Cath, D. (Daniëlle), Cavallini, M.C. (Maria), Chouinard, S., Coric, V. (Vladimir), Cullen, C., Delorme, R. (Richard), Denys, D.A.J.P. (Damiaan), Derks, E.M. (Eske), Dion, Y. (Yves), Rosário, M.C. (Maria), Eapen, C.E. (Chundamannil Eapen), Evans, P., Falkai, P. (Peter), Fernandez, T.V. (Thomas), Garrido, H. (Helena), Geller, D. (Daniel), Grabe, H.J. (Hans Jörgen), Grados, M. (Marco), Greenberg, B.D. (Benjamin), Gross-Tsur, V. (Varda), Grünblatt, E. (Edna), Heiman, M.L. (Mark), Hemmings, S.M.J. (Sian), Herrera, L.D. (Luis), Hounie, A.G. (Ana), Jankovic, J. (Joseph), Kennedy, J.L., King, R.A., Kurlan, R., Lanzagorta, N. (Nuria), Leboyer, M. (Marion), Leckman, J.F., Lennertz, L. (Leonhard), Lochner, C. (Christine), Lowe, T.L. (Thomas), Lyon, H.N. (Helen), MacCiardi, F. (Fabio), Maier, W. (Wolfgang), McCracken, J.T. (James), McMahon, W.M. (William), Murphy, D.L. (Dennis), Naarden, A.L. (Allan), Nurmi, E. (Erika), Pakstis, A.J., Pato, C. (Carlos), Piacentini, J. (John), Pittenger, C. (Christopher), Pollak, M.N. (Michael), Reus, V.I. (Victor), Richter, M.A. (Margaret), Riddle, M. (Mark), Robertson, M.M., Rosenberg, D. (David), Rouleau, G.A., Ruhrmann, S. (Stephan), Sampaio, A.S. (Aline), Samuels, J. (Jonathan), Sandor, P. (Paul), Sheppard, B. (Brooke), Singer, H.S. (Harvey), Smit, J.H. (Jan), Stein, D.J. (Dan), Tischfield, J.A. (Jay), Vallada, H. (Homero), Veenstra-Vanderweele, J. (Jeremy), Walitza, S. (Susanne), Wang, Y. (Ying), Wendland, A. (Annika), Shugart, Y.Y., Miguel, E.C. (Euripedes), Nicolini, H. (Humberto), Oostra, B.A. (Ben), Moessner, R. (Rainald), Wagner, M. (Michael), Ruiz-Linares, A. (Andres), Heutink, P. (Peter), Nestadt, G. (Gerald), Freimer, N.B. (Nelson), Petryshen, T.L. (Tracey), Posthuma, D. (Danielle), Jenike, M.A. (Michael), Cox, N.J. (Nancy), Hanna, G.L. (Gregory), Brentani, H. (Helena), Scherer, S.W. (Stephen), Arnold, P.D. (Paul), Stewart, S.E., Mathews, C., Knowles, J.A. (James A), Cook, E.H. (Edwin), Pauls, D.L. (David), Wang, K. (Kai), Scharf, J.M., Neale, B.M. (Benjamin), McGrath, L.M., Yu, D. (D.), Marshall, C.R. (Christian), Davis, L.K. (Lea), Thiruvahindrapuram, B. (Bhooma), Li, B. (Bingbin), Cappi, C. (Carolina), Gerber, G. (Gloria), Wolf, A. (Anneke) de, Schroeder, F.A. (Frederick), Osiecki, L. (Lisa), O'Dushlaine, C. (Colm), Kirby, A. (Andrew), Illmann, C. (Cornelia), Haddad, S. (Stephen), Gallagher, P. (Patience), Fagerness, J. (Jesen), Barr, C.L. (Cathy), Bellodi, L. (Laura), Benarroch, F. (Fortu), Bienvenu, O.J. (Oscar), Black, D.W. (Donald), Bloch, J. (Jocelyne), Bruun, R.D. (Ruth), Budman, C.L. (Cathy), Camarena, B. (Beatriz), Cath, D. (Daniëlle), Cavallini, M.C. (Maria), Chouinard, S., Coric, V. (Vladimir), Cullen, C., Delorme, R. (Richard), Denys, D.A.J.P. (Damiaan), Derks, E.M. (Eske), Dion, Y. (Yves), Rosário, M.C. (Maria), Eapen, C.E. (Chundamannil Eapen), Evans, P., Falkai, P. (Peter), Fernandez, T.V. (Thomas), Garrido, H. (Helena), Geller, D. (Daniel), Grabe, H.J. (Hans Jörgen), Grados, M. (Marco), Greenberg, B.D. (Benjamin), Gross-Tsur, V. (Varda), Grünblatt, E. (Edna), Heiman, M.L. (Mark), Hemmings, S.M.J. (Sian), Herrera, L.D. (Luis), Hounie, A.G. (Ana), Jankovic, J. (Joseph), Kennedy, J.L., King, R.A., Kurlan, R., Lanzagorta, N. (Nuria), Leboyer, M. (Marion), Leckman, J.F., Lennertz, L. (Leonhard), Lochner, C. (Christine), Lowe, T.L. (Thomas), Lyon, H.N. (Helen), MacCiardi, F. (Fabio), Maier, W. (Wolfgang), McCracken, J.T. (James), McMahon, W.M. (William), Murphy, D.L. (Dennis), Naarden, A.L. (Allan), Nurmi, E. (Erika), Pakstis, A.J., Pato, C. (Carlos), Piacentini, J. (John), Pittenger, C. (Christopher), Pollak, M.N. (Michael), Reus, V.I. (Victor), Richter, M.A. (Margaret), Riddle, M. (Mark), Robertson, M.M., Rosenberg, D. (David), Rouleau, G.A., Ruhrmann, S. (Stephan), Sampaio, A.S. (Aline), Samuels, J. (Jonathan), Sandor, P. (Paul), Sheppard, B. (Brooke), Singer, H.S. (Harvey), Smit, J.H. (Jan), Stein, D.J. (Dan), Tischfield, J.A. (Jay), Vallada, H. (Homero), Veenstra-Vanderweele, J. (Jeremy), Walitza, S. (Susanne), Wang, Y. (Ying), Wendland, A. (Annika), Shugart, Y.Y., Miguel, E.C. (Euripedes), Nicolini, H. (Humberto), Oostra, B.A. (Ben), Moessner, R. (Rainald), Wagner, M. (Michael), Ruiz-Linares, A. (Andres), Heutink, P. (Peter), Nestadt, G. (Gerald), Freimer, N.B. (Nelson), Petryshen, T.L. (Tracey), Posthuma, D. (Danielle), Jenike, M.A. (Michael), Cox, N.J. (Nancy), Hanna, G.L. (Gregory), Brentani, H. (Helena), Scherer, S.W. (Stephen), Arnold, P.D. (Paul), Stewart, S.E., Mathews, C., Knowles, J.A. (James A), Cook, E.H. (Edwin), Pauls, D.L. (David), Wang, K. (Kai), Scharf, J.M., and Neale, B.M. (Benjamin)

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.

Published
2014
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41. Fluvoxamine treatment and D(2) receptors: a PET study on OCD drug-naive patients

Author

Moresco R.M. 1, 2, 3, Pietra L. 2, Henin M. 4, Panzacchi A .3, Locatelli M. 4, Bonaldi L. 1, Carpinelli A. 1, Gobbo C. 3, Bellodi L. 4, 5, Perani D. 1, and Fazio F. 1

Subjects
mental disorders, Emission tomography, Obsessive-compulsive disorder, Molecular imaging, Dopamine receptor, antidepressant, Drug na1ve
Abstract

Changes in D2 receptors during antidepressant therapy have been reported in patients with major depressive disorder using PET/SPET. The aim of this study was to evaluate modifications in D2 receptors that might occur in patients affected by obsessive-compulsive disorder (OCD) during serotonin reuptake sites inhibitors (SSRIs). To this purpose, we measured the in vivo binding of [11C]raclopride ([11C]Rac)in the brain of a group of OCD naïve patients before and after the repeated administration of the inhibitor SSRI fluvoxamine. Eight patients with a Diagnostic and Statistical Manual of Mental Disorders IVth edition diagnosis of OCD completed the study undergoing a PET scan and a complete clinical evaluation before and during treatment with fluvoxamine. Patients have been compared also with a group of nine age-matched normal volunteers. Fluvoxamine treatment significantly improved clinical symptoms and increased [11C]Rac binding potential (BP) in the basal ganglia of OCD patients (7.55.2, 6.96.9, and 9.99.3% in dorsal caudate, dorsal putamen, and ventral basal ganglia, respectively; p

Published
2007

49. Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

Author

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

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 b

Published
2013
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50. Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

Author

Davis, LK, Yu, DM, Keenan, CL, Gamazon, ER, Konkashbaev, AI, Derks, EM, Neale, BM, Yang, Jiaqi, Lee, SH, Evans, P, Barr, CL, Bellodi, L, Benarroch, F, Berrio, GB, Bienvenu, OJ, Bloch, MH, Blom, RM, Bruun, RD, Budman, CL, Camarena, B, Campbell, D, Cappi, C, Silgado, JCC, Cath, DC, Cavallini, MC, Chavira, DA, Chouinard, S, Conti, DV, Cook, EH, Coric, V, Cullen, BA, Deforce, D, Delorme, R, Dion, Y, Edlund, CK, Egberts, K, Falkai, P, Fernandez, TV, Gallagher, PJ, Garrido, H, Geller, D, Girard, SL, Grabe, HJ, Grados, MA, Greenberg, BD, Gross-Tsur, V, Haddad, S, Heiman, GA, Hemmings, SMJ, Hounie, AG, Illmann, C, Jankovic, J, Jenike, MA, Kennedy, JL, King, RA, Kremeyer, B, Kurlan, R, Lanzagorta, N, Leboyer, M, Leckman, JF, Lennertz, L, Liu, C, Lochner, C, Lowe, TL, Macciardi, F, McCracken, JT, McGrath, LM, Restrepo, SCM, Moessner, R, Morgan, J, Muller, Heike, Murphy, DL, Naarden, AL, Ochoa, WC, Ophoff, RA, Osiecki, L, Pakstis, AJ, Pato, MT, Pato, CN, Piacentini, J, Pittenger, C, Pollak, Y, Rauch, SL, Renner, TJ, Reus, VI, Richter, MA, Riddle, MA, Robertson, MM, Romero, R, Rosario, MC, Rosenberg, D, Rouleau, GA, Ruhrmann, S, Ruiz-Linares, A, Sampaio, AS, Samuels, J, Sandor, P, Sheppard, B, Singer, HS, Smit, JH, Stein, DJ, Strengman, E, Tischfield, JA, Duarte, AVV, Vallada, H, Van Nieuwerburgh, F, Veenstra-VanderWeele, J, Walitza, S, Wang, Y, Wendland, JR, Westenberg, HGM, Shugart, YY, Miguel, EC, McMahon, W, Wagner, M, Nicolini, H, Posthuma, Daniëlle, Hanna, GL, Heutink, P, Denys, D, Arnold, PD, Oostra, Ben, Nestadt, G, Freimer, NB, Pauls, DL, Wray, NR, Stewart, SE, Mathews, CA, Knowles, JA, Cox, NJ, Scharf, JM, Davis, LK, Yu, DM, Keenan, CL, Gamazon, ER, Konkashbaev, AI, Derks, EM, Neale, BM, Yang, Jiaqi, Lee, SH, Evans, P, Barr, CL, Bellodi, L, Benarroch, F, Berrio, GB, Bienvenu, OJ, Bloch, MH, Blom, RM, Bruun, RD, Budman, CL, Camarena, B, Campbell, D, Cappi, C, Silgado, JCC, Cath, DC, Cavallini, MC, Chavira, DA, Chouinard, S, Conti, DV, Cook, EH, Coric, V, Cullen, BA, Deforce, D, Delorme, R, Dion, Y, Edlund, CK, Egberts, K, Falkai, P, Fernandez, TV, Gallagher, PJ, Garrido, H, Geller, D, Girard, SL, Grabe, HJ, Grados, MA, Greenberg, BD, Gross-Tsur, V, Haddad, S, Heiman, GA, Hemmings, SMJ, Hounie, AG, Illmann, C, Jankovic, J, Jenike, MA, Kennedy, JL, King, RA, Kremeyer, B, Kurlan, R, Lanzagorta, N, Leboyer, M, Leckman, JF, Lennertz, L, Liu, C, Lochner, C, Lowe, TL, Macciardi, F, McCracken, JT, McGrath, LM, Restrepo, SCM, Moessner, R, Morgan, J, Muller, Heike, Murphy, DL, Naarden, AL, Ochoa, WC, Ophoff, RA, Osiecki, L, Pakstis, AJ, Pato, MT, Pato, CN, Piacentini, J, Pittenger, C, Pollak, Y, Rauch, SL, Renner, TJ, Reus, VI, Richter, MA, Riddle, MA, Robertson, MM, Romero, R, Rosario, MC, Rosenberg, D, Rouleau, GA, Ruhrmann, S, Ruiz-Linares, A, Sampaio, AS, Samuels, J, Sandor, P, Sheppard, B, Singer, HS, Smit, JH, Stein, DJ, Strengman, E, Tischfield, JA, Duarte, AVV, Vallada, H, Van Nieuwerburgh, F, Veenstra-VanderWeele, J, Walitza, S, Wang, Y, Wendland, JR, Westenberg, HGM, Shugart, YY, Miguel, EC, McMahon, W, Wagner, M, Nicolini, H, Posthuma, Daniëlle, Hanna, GL, Heutink, P, Denys, D, Arnold, PD, Oostra, Ben, Nestadt, G, Freimer, NB, Pauls, DL, Wray, NR, Stewart, SE, Mathews, CA, Knowles, JA, Cox, NJ, and Scharf, JM

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.

Published
2013

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