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1. Stemming the tide of mental health problems in young people: Challenges and potential solutions.

Author

Eapen V, Stylianakis A, Scott E, Milroy H, Bowden M, Haslam R, and Stathis S

Subjects
Child, Adolescent, Humans, Adult, Mental Health, Pandemics, COVID-19, Mental Disorders therapy, Mental Disorders epidemiology, Mental Health Services
Abstract

One in five people experience clinically relevant mental health problems before the age of 25 years. Furthermore, in Australia, one in seven children are reported to experience a mental health disorder. Consequently, there has been a steady increase in demand for mental health services for children and young people, and this has been compounded by the COVID-19 pandemic. Unfortunately, currently many children and young people with mental health difficulties are not accessing appropriate and/or timely care, with individuals and families finding it increasingly difficult to access and navigate suitable services. In part, this is related to the fragmented and isolated manner in which child mental health services are operating. To address the current issues in access to appropriate child and adolescent mental health care in Australia, a novel Integrated Continuum of Connect and Care model is proposed to integrate relevant services along a tiered care pathway. The aim of this model is to facilitate timely access to mental health services that meet the specific needs of each child/young person and their family. This model will function within co-located service hubs that integrate health care through a comprehensive assessment followed by a link up to relevant services. The Integrated Continuum of Connect and Care has the potential to pave the way for unifying the fragmented child and youth mental health system in Australia.

Published
2023
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2. E-mental health in child psychiatry during COVID-19: an initial attitudinal study.

Author

Eapen V, Dadich A, Balachandran S, Dani A, Howari R, Sequeria AZ, and Singer JD

Subjects
Child, Humans, New South Wales epidemiology, Attitude of Health Personnel, COVID-19 epidemiology, Child Psychiatry organization & administration, Mental Disorders therapy, Telemedicine organization & administration
Abstract

Objective: COVID-19 propelled e-mental health within the Australian health system. It is important to learn from this to inform mental healthcare during future crises., Method: A lexical analysis was conducted of clinician reflections during COVID-19 as they delivered psychiatry services to children and families in New South Wales ( n = 6) and transitioned to e-mental health., Results: E-mental health can extend the reach of, and access to psychiatry services, particularly for individuals disadvantaged by inequity. Yet e-mental health can be problematic. It is partly contingent on technological prowess, equipment, internet access as well as space and privacy. Relatedly, e-mental health can hinder clinician capacity to conduct examinations, monitor child development as well as assess risk and the need for child protection., Conclusions: Given the benefits and limitations of e-mental health, a model that supports face-to-face mental healthcare and e-mental health may be of value. This model would require practical, yet flexible policies and protocols that protect the privacy of children and families, safeguard them from harm, and respect the needs and preferences of children, families and clinicians.

Published
2021
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3. The Differential Impact of Tourette's Syndrome and Comorbid Diagnosis on the Quality of Life and Functioning of Diagnosed Children and Adolescents.

Author

O'Hare D, Helmes E, Reece J, Eapen V, and McBain K

Subjects
Adolescent, Child, Comorbidity, Female, Humans, Male, Mental Disorders epidemiology, Tourette Syndrome epidemiology, Mental Disorders psychology, Quality of Life psychology, Tourette Syndrome psychology
Abstract

Problem: Tourette's syndrome (TS) is a neuropsychiatric disorder associated with adverse outcomes. High rates of comorbidity (80-90%) complicate presentation, yet the relationship among TS, common comorbid diagnoses, and adversity is not well understood. This research investigated the impact of comorbidity, and the discrete effects of common comorbid diagnoses, on quality of life (QoL) and functioning of youth with TS., Methods: A community sample of parents of youth with TS (n = 86) participated in this survey-based study. Differences in QoL (Pediatric Quality of Life Inventory) and rates of psychological, behavioral, and social difficulties (Strength and Difficulties Questionnaire) reported for youth with or without comorbid disorder were determined, in addition to outcomes associated with individual disorders., Findings: Parametric and nonparametric analyses revealed strong associations between comorbidity and decreased global QoL, impaired emotional and school functioning, and increased emotional symptomatology (p < .001). The impact of individual comorbid disorders was restricted and disorder specific, and TS was uniquely associated with impaired social functioning and peer relationship problems., Conclusions: Understanding the risks associated with TS, particularly to psychosocial well-being, and the specific risks accompanying individual comorbid disorders, may improve assessment, prioritization of treatment goals, and interventions targeting the individual, multidimensional needs of youth with TS., (© 2016 Wiley Periodicals, Inc.)

Published
2016
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5. DSM 5 and child psychiatric disorders: what is new? What has changed?

Author

Eapen V and Črnčec R

Subjects
Anxiety Disorders classification, Anxiety Disorders diagnosis, Child, Humans, Obsessive-Compulsive Disorder classification, Obsessive-Compulsive Disorder diagnosis, Diagnostic and Statistical Manual of Mental Disorders, Mental Disorders classification, Mental Disorders diagnosis
Abstract

The significant changes in DSM 5 as these relate to a number of the child psychiatric disorders are reviewed by several authors in this special issue: In this paper we address some of the changes in the conceptual organisation of DSM 5 and specifically focus on anxiety and related disorders. In the case of child and adolescent psychiatry, the most notable feature is that the chapter on Disorders Usually First Diagnosed in infancy, Childhood or Adolescence has been deleted. Instead, a new chapter in DSM 5 describes Neurodevelopmental Disorders which typically manifest early in development. Further, an expectation had been built that DSM would be based on the latest data in neuroscience and that a clear direction towards a mixed dimensional and categorical approach would be evident. This has been the case with some disorders and a notable example is the removal of Obsessive Compulsive Disorder (OCD) from the Anxiety Disorder chapter and placement with other related disorders that share similar neurobiology and treatment response. In this regard, the addition in DSM 5 of a new specifier "tic-related" to OCD is worth noting as there is emerging evidence that differential treatment response exists when tics are associated with OCD. The same situation applies to tics with ADHD, thus presenting the argument for a dimensional approach to Tic Spectrum Disorder (TSD) incorporating categories such as those with tics only, tics with OCD, tics with ADHD etc. to be given due consideration in the future. Another important change that clinicians in the field of child psychiatry will no doubt notice is the demise of the multiaxial classification. Instead, DSM 5 has moved back to a nonaxial documentation of diagnosis with separate notations for important psychosocial and contextual factors as well as level of functioning and disability. Clinicians are urged, however, to continue to recognise the need to understand how symptoms and behaviours might have arisen and assess relevant contextual factors such as the family relationships, quality of care, any history of abuse, and so on. Further, the move to harmonise DSM 5 with the structure of ICD 11 (scheduled for release in 2015) should make understanding and familiarising oneself with the two major classificatory systems easier in the future., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Published
2014
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6. Developmental and mental health disorders: two sides of the same coin.

Author

Eapen V

Subjects
Child, Humans, Risk Factors, Developmental Disabilities complications, Mental Disorders complications
Abstract

Children with developmental disorders (DD) are at substantially greater risk of developing mental health problems compared to typically developing children. However, the mental health co-morbidity is often missed or hidden in the context of DD leading to reduced quality of life and increased burden of care. Mental health problems in the context of DD also result in less optimal school and post-school outcomes with reduced opportunities for employment and community participation. There is also considerable overlap in the risk factors for both conditions, and these follow a cumulative risk model. Although awareness among clinicians and the public is improving, there is paucity of theoretical models, early identification frameworks as well as care pathways for interventions. This paper presents a framework for evaluating developmental vulnerability that highlights common risk factors for developmental and mental health disorders., (Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2014
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7. Metabolic syndrome in an adolescent psychiatric unit.

Author

Dullur P, Eapen V, and Trapolini T

Subjects
Adolescent, Body Mass Index, Female, Humans, Inpatients statistics & numerical data, Male, Mental Disorders drug therapy, Metabolic Syndrome etiology, Antipsychotic Agents adverse effects, Mental Disorders epidemiology, Metabolic Syndrome epidemiology
Published
2012
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8. Preschool psychopathology reported by parents in 23 societies: testing the seven-syndrome model of the child behavior checklist for ages 1.5-5.

Author

Ivanova MY, Achenbach TM, Rescorla LA, Harder VS, Ang RP, Bilenberg N, Bjarnadottir G, Capron C, De Pauw SS, Dias P, Dobrean A, Doepfner M, Duyme M, Eapen V, Erol N, Esmaeili EM, Ezpeleta L, Frigerio A, Gonçalves MM, Gudmundsson HS, Jeng SF, Jetishi P, Jusiene R, Kim YA, Kristensen S, Lecannelier F, Leung PW, Liu J, Montirosso R, Oh KJ, Plueck J, Pomalima R, Shahini M, Silva JR, Simsek Z, Sourander A, Valverde J, Van Leeuwen KG, Woo BS, Wu YT, Zubrick SR, and Verhulst FC

Subjects
Affective Symptoms diagnosis, Affective Symptoms epidemiology, Affective Symptoms psychology, Child Behavior Disorders diagnosis, Child Behavior Disorders epidemiology, Child Behavior Disorders psychology, Child, Preschool, Cross-Sectional Studies, Female, Humans, Incidence, Infant, Male, Mental Disorders psychology, Models, Psychological, Psychometrics statistics & numerical data, Reproducibility of Results, Social Behavior Disorders diagnosis, Social Behavior Disorders epidemiology, Social Behavior Disorders psychology, Syndrome, Checklist, Cross-Cultural Comparison, Mass Screening statistics & numerical data, Mental Disorders diagnosis, Mental Disorders epidemiology, Personality Assessment statistics & numerical data
Abstract

Objective: To test the fit of a seven-syndrome model to ratings of preschoolers' problems by parents in very diverse societies., Method: Parents of 19,106 children 18 to 71 months of age from 23 societies in Asia, Australasia, Europe, the Middle East, and South America completed the Child Behavior Checklist for Ages 1.5-5 (CBCL/1.5-5). Confirmatory factor analyses were used to test the seven-syndrome model separately for each society., Results: The primary model fit index, the root mean square error of approximation (RMSEA), indicated acceptable to good fit for each society. Although a six-syndrome model combining the Emotionally Reactive and Anxious/Depressed syndromes also fit the data for nine societies, it fit less well than the seven-syndrome model for seven of the nine societies. Other fit indices yielded less consistent results than the RMSEA., Conclusions: The seven-syndrome model provides one way to capture patterns of children's problems that are manifested in ratings by parents from many societies. Clinicians working with preschoolers from these societies can thus assess and describe parents' ratings of behavioral, emotional, and social problems in terms of the seven syndromes. The results illustrate possibilities for culture-general taxonomic constructs of preschool psychopathology. Problems not captured by the CBCL/1.5-5 may form additional syndromes, and other syndrome models may also fit the data., (Copyright © 2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Published
2010
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9. Clinical features and associated psychopathology in a Tourette syndrome cohort.

Author

Eapen V, Fox-Hiley P, Banerjee S, and Robertson M

Subjects
Adolescent, Adult, Age Factors, Aged, Cohort Studies, Female, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, Psychological Tests, Risk Factors, Severity of Illness Index, Sex Factors, United Kingdom, Mental Disorders etiology, Mental Disorders pathology, Tourette Syndrome pathology, Tourette Syndrome psychology
Abstract

Objective: This study explored in detail the association between tic symptomatology, related clinical variables, and psychopathology in 91 consecutive adult TS subjects from a UK clinic., Methods: Consecutive patients from a specialized Tourette clinic who met the DSM-III criteria for TS were evaluated using standardized rating scales for Tourette syndrome and other psychopathology., Results: The male female ratio in our cohort was 1.8:1. Significantly more males had an earlier age at onset of TS and history of birth complications. Obsessive compulsive behaviors in the patient was positively correlated with presence of attention deficit hyperactivity disorder and self-injurious behaviors. With regard to adult psychopathology, principal components factor analysis yielded two factors, 'obsessionality' and 'anxiety/depression', which accounted for 72% of the variance., Conclusion: Our results support the high occurrence of anxiety, depression and obsessionality in adult TS subjects.

Published
2004
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10. Help-seeking for mental health problems of children: preferences and attitudes in the United Arab Emirates.

Author

Eapen V and Ghubash R

Subjects
Adult, Child, Community Mental Health Services statistics & numerical data, Family Health ethnology, Female, Humans, Male, Mental Disorders ethnology, Parent-Child Relations, United Arab Emirates ethnology, Arabs psychology, Mental Disorders therapy, Parents psychology, Patient Acceptance of Health Care psychology
Abstract

Parental attitudes, religious beliefs, and other sociocultural factors have all been recognized to influence help-seeking patterns in relation to child psychiatric morbidity. But few systematic studies have addressed this issue in the Arab region. In this study, we investigated the help-seeking preferences for mental health problems in a community sample. 325 parents contacted as part of a community-based study of child psychiatric disorders were surveyed using a semistructured interview schedule. Only 38% of those surveyed indicated they would seek help from mental health specialists in the event of psychiatric problems developing in a family member, including their children. Main reasons given for nonconsultation were reluctance to acknowledge that a member of their family has a mental illness, stigma attached to attending mental health services, and the skepticism about the usefulness of mental health services. Willingness to utilize psychiatric services was associated with better parental education, occupation, and socioeconomic status. Our results suggest that sociocultural factors and parental perceptions may have a major effect on whether children with psychiatric disturbance receive professional help.

Published
2004
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11. Children with psychiatric disorders: the A1 Ain Community Psychiatric Survey.

Author

Eapen V, Jakka ME, and Abou-Saleh MT

Subjects
Adolescent, Child, Community Mental Health Services, Female, Humans, Male, Mental Disorders diagnosis, Prevalence, Mental Disorders epidemiology, Surveys and Questionnaires
Abstract

Objective: The prevalence of child psychiatric morbidity in the community is unknown in most developing countries, including those in the Arab region., Method: An epidemiologic study was carried out to estimate the prevalence of psychiatric morbidity and to determine the sociodemographic correlates in a sample of children in the community, aged 6 to 18 years, in A1 Ain, United Arab Emirates (UAE)., Results: We obtained a prevalence rate of 22.2% for overall morbidity, as classified in the DSM-1V, and 14.3% for those with significant dysfunction, with the most common diagnosis being mood disorders. Female sex, large family size, chronic life difficulties, family history of psychiatric disorder, and alcohol-related problems in a family member were significantly associated with DSM-IV diagnosis., Conclusion: Although the prevalence and symptomatology in this Middle East community are similar to those in Western studies, none of these children had received professional help, suggesting serious deficiencies in mental health care services in the country.

Published
2003
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12. Prevalence of tics and Tourette syndrome in an inpatient adult psychiatry setting.

Author

Eapen V, Laker M, Anfield A, Dobbs J, and Robertson MM

Subjects
Adolescent, Adult, Comorbidity, Cross-Sectional Studies, Female, Genetic Predisposition to Disease, Hospitals, University, Humans, Incidence, London epidemiology, Male, Mental Disorders diagnosis, Mental Disorders genetics, Mental Disorders psychology, Psychiatric Department, Hospital statistics & numerical data, Psychiatric Status Rating Scales, Tics diagnosis, Tics genetics, Tics psychology, Tourette Syndrome diagnosis, Tourette Syndrome genetics, Tourette Syndrome psychology, Mental Disorders epidemiology, Tics epidemiology, Tourette Syndrome epidemiology
Abstract

Objective: Given the widely recognized genetic basis for Gilles de la Tourette syndrome (TS) and the suggestion that the putative TS gene(s) may be expressed as or associated with a variety of psychiatric illnesses, this study was undertaken to assess the prevalence of tics and TS in a psychiatric inpatient population., Design: Cross-sectional study., Setting and Patients: 200 consecutive adult patients who were admitted to the psychiatric wards of University College London Teaching Hospitals., Outcome Measures: TS and related behaviours, as assessed by the comprehensive semi-structured National Hospital Interview Schedule., Results: None of the 200 patients had definite TS, but 2 were observed to have motor tics; 10 had a history of tics (present for less than a year), and 7 reported a family history of tics. Thus, 19 (9.5%) inpatients qualified for inclusion in a broadly defined TS diathesis. These rates are significantly lower than those reported in a similar community based epidemiological study of adolescents (p = 0.018)., Conclusions: Our findings do not support the theory that TS and related behaviours are over-represented among adult inpatients with psychiatric illnesses.

Published
2001

13. A controlled study of psychiatric morbidity among developmentally disabled children in the United Arab Emirates.

Author

Swadi H and Eapen V

Subjects
Age Distribution, Case-Control Studies, Child, Child, Preschool, Comorbidity, Cross-Sectional Studies, Developmental Disabilities psychology, Disabled Children psychology, Female, Humans, Incidence, Male, Mental Disorders diagnosis, Morbidity trends, Probability, Reference Values, Risk Factors, Sex Distribution, United Arab Emirates epidemiology, Developmental Disabilities epidemiology, Disabled Children statistics & numerical data, Mental Disorders epidemiology
Abstract

A cross-sectional study of the prevalence of psychiatric problems among 26 children each with a learning disability (mental retardation) and specific speech disorder was conducted in an Arab population using the Rutter Behavioural Scale, and compared with a community sample of 100 control children matched for age. The prevalence of psychiatric problems, as identified by both the parents and the teachers was 35, 19 and 4 per cent respectively, in the learning disabled, speech impaired and control groups. Children with global disability or mental retardation showed significantly higher rates of psychiatric morbidity than those with specific speech disorder, both of which were significantly higher than that in the control group. Higher rates of psychiatric problems noted in the developmentally disabled children may be the result of specific socio-demographic and cultural factors in addition to neurodevelopmental factors and low IQ.

Published
2000
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14. School mental health screening: a model for developing countries.

Author

Eapen V, al-Gazali LI, Bin-Othman S, Abou-Saleh MT, el-Nasser KA, Ramzy R, Selwans SB, Skaik MB, Awad F, el-Faki MM, el-Habish HA, Hafez KM, Ibrahim FM, Todary S, and Yaghi OY

Subjects
Child, Cost-Benefit Analysis, Humans, Models, Organizational, United Arab Emirates, Developing Countries, Mass Screening organization & administration, Mental Disorders prevention & control, School Health Services organization & administration
Abstract

Using the experience derived from a screening programme of all school-going children in the Al Ain District, United Arab Emirates, this article reports on a cost-effective model that can be used in other developing countries. The need for training child health and school professionals in identifying mental and developmental disorders is discussed.

Published
1999
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15. Mental health problems among schoolchildren in United Arab Emirates: prevalence and risk factors.

Author

Eapen V, al-Gazali L, Bin-Othman S, and Abou-Saleh M

Subjects
Adolescent, Case-Control Studies, Child, Cohort Studies, Confidence Intervals, Cross-Sectional Studies, Family Health ethnology, Female, Health Surveys, Humans, Male, Odds Ratio, Prevalence, Risk Factors, Sex Factors, United Arab Emirates epidemiology, Mental Disorders epidemiology
Abstract

Objective: To examine child psychiatric morbidity in an Arab culture., Method: Emotional and behavioral problems were investigated in 3,278 schoolchildren aged 6 to 15 years using a two-stage epidemiological study in Al Ain District, United Arab Emirates. Children were screened using standardized questionnaires completed by parents and school physicians in the first stage, and a stratified random sample were interviewed by a child psychiatrist in the second stage., Results: 23.9% of children were reported to have a mental health problem by either the parent or the school health physician. Boys were more often reported to be having problems than girls (1.8:1). Using the Rutter A2 scale for parents, the prevalence estimate for behavioral disorders was 16.5%. The weighted prevalence for DSM-IV disorders was 10.4% for the entire population. The presence of certain culture-specific risk factors such as male gender, number of children in the household, polygamy, and low socioeconomic status were identified for psychiatric disorders. A positive family history and consanguinity were the most significant factors associated with learning disorders., Conclusions: The prevalence rates of child psychiatric disorders and the symptomatology observed in this Middle East community are similar to those reported in Western studies.

Published
1998
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16. Psychiatric morbidity in HIV infected individuals.

Author

Jacob KS, Eapen V, John JK, and John TJ

Subjects
Acquired Immunodeficiency Syndrome complications, Adult, Female, HIV Infections complications, Humans, Male, Middle Aged, Acquired Immunodeficiency Syndrome psychology, HIV Infections psychology, Mental Disorders complications
Abstract

Forty six subjects infected with the human immunodeficiency virus (HIV) were followed up, for recording psychiatric morbidity if any, before and after the information regarding their HIV status was revealed to them. Among these, four patients had the AIDS syndrome, while 42 individuals were HIV carriers. The pre-information morbidity in the AIDS group included two individuals who presented with delirium and one with an adjustment disorder. The psychiatric diagnosis among the HIV carriers revealed one patient with major depression, four with adjustment disorders and four with alcohol dependence syndrome. The additional morbidity after the diagnoses was revealed included major depression and adjustment disorders which could be managed by psychological intervention and counselling in most cases. The individual who developed major depression later, committed suicide. The study though preliminary in nature, suggests that it may be beneficial to include psychiatric management as part of the general care of individuals with HIV infection.

Published
1991

17. Autism-related dietary preferences mediate autism-gut microbiome associations

Author

Yap, CX, Henders, AK, Alvares, GA, Wood, DLA, Krause, L, Tyson, GW, Restuadi, R, Wallace, L, McLaren, T, Hansell, NK, Cleary, D, Grove, R, Hafekost, C, Harun, A, Holdsworth, H, Jellett, R, Khan, F, Lawson, LP, Leslie, J, Frenk, ML, Masi, A, Mathew, NE, Muniandy, M, Nothard, M, Miller, JL, Nunn, L, Holtmann, G, Strike, LT, de Zubicaray, GI, Thompson, PM, McMahon, KL, Wright, MJ, Visscher, PM, Dawson, PA, Dissanayake, C, Eapen, V, Heussler, HS, McRae, AF, Whitehouse, AJO, Wray, NR, and Gratten, J

Subjects
mental disorders, 06 Biological Sciences, 11 Medical and Health Sciences, behavioral disciplines and activities, Developmental Biology
Abstract

There is increasing interest in the potential contribution of the gut microbiome to autism spectrum disorder (ASD). However, previous studies have been underpowered and have not been designed to address potential confounding factors in a comprehensive way. We performed a large autism stool metagenomics study (n = 247) based on participants from the Australian Autism Biobank and the Queensland Twin Adolescent Brain project. We found negligible direct associations between ASD diagnosis and the gut microbiome. Instead, our data support a model whereby ASD-related restricted interests are associated with less-diverse diet, and in turn reduced microbial taxonomic diversity and looser stool consistency. In contrast to ASD diagnosis, our dataset was well powered to detect microbiome associations with traits such as age, dietary intake, and stool consistency. Overall, microbiome differences in ASD may reflect dietary preferences that relate to diagnostic features, and we caution against claims that the microbiome has a driving role in ASD.

Published
2021

18. Spectrum or subtypes? A latent profile analysis of restricted and repetitive behaviours in autism

Author

Zheng, L, Grove, R, and Eapen, V

Subjects
mental disorders, Rehabilitation
Abstract

© 2018 Elsevier Ltd Background: Autism Spectrum Disorder (ASD) is a heterogeneous condition. One way of understanding this heterogeneity is by investigating whether homogenous subgroups within the autism population exist. Some studies have attempted to do this by looking at social and communication skills. However, few studies have looked at subtyping using restricted and repetitive behaviours. While restricted and repetitive behaviours form part of the core features of autism, their presentation is diverse across different individuals on the spectrum. The aim of this study was to determine if restricted and repetitive behaviours could be used to identify potential subtypes of autism. Method: This study used unsupervised clustering algorithms to differentiate subgroups of individuals on the autism spectrum based on their scores on the Repetitive Behaviour Scale-Revised (RBS-R). Results: Three groups were found that reported low, medium and high levels of restricted and repetitive behaviours. These groups also differed on a range of clinical measures including problematic behaviours, autistic traits and adaptive behaviours. Conclusions: Our findings indicate that subgroups of individuals with autism can be identified based on their level of restricted and repetitive behaviours. This highlights that restricted and repetitive behaviours may be best understood under a dimensional continuum of severity. This has implications for our understanding of the non-social characteristics of autism.

Published
2019

19. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Author

Laura M. Thornton, Paul Lichtenstein, Verneri Anttila, Diego Albani, Josep Antoni Ramos-Quiroga, Roger A.H. Adan, Monika Schlögelhofer, Stephen Sanders, Enrique Castelao, Klaus Berger, Nina Dalkner, Urs Heilbronner, Engilbert Sigurdsson, Pablo Mir, Fuquan Zhang, James T.R. Walters, Patrick F. Sullivan, Fragiskos Gonidakis, F. Kyle Satterstrom, Sara Marsal, Per Hoffmann, Amy Perry, Valentina Ciullo, Beate Herpertz-Dahlmann, Catharina Lavebratt, Kieran C. Murphy, Tammy Hedderly, Hyun Ju Hong, Evald Saemundsen, Sascha B. Fischer, Hailiang Huang, Andrew D. Grotzinger, Nienke Vulink, Murray B. Stein, Mark A. Frye, Laura J. Scott, David Curtis, Todd Lencz, Janiece E. DeSocio, Richard A. Belliveau, Eduard Vieta, Andrea Dietrich, Wade H. Berrettini, Kenneth S. Kendler, Marquis P. Vawter, Paul S. Nestadt, Michael E. Talkowski, Manuel Mattheisen, Ingrid Agartz, Elisa Docampo, Bernhard T. Baune, Stefan Ehrlich, Jolanta Lissowska, Felecia Cerrato, Terje Nærland, Robin M. Murray, Jennifer Reichert, Annette M. Hartmann, Hannelore Ehrenreich, Howard J. Edenberg, Katherine A. Halmi, Qingqin S. Li, Peristera Paschou, Marie Bækvad-Hansen, Esther Walton, Alessio Maria Monteleone, Ted Reichborn-Kjennerud, Frank Bellivier, Jungeun Song, D. Blake Woodside, Young Shin Kim, Jochen Seitz, Jacques Pantel, Palmiero Monteleone, Erika L. Nurmi, Rodney J. Scott, Kang Sim, Ekaterina A. Khramtsova, Udo Dannlowski, Rolf Adolfsson, Danielle Posthuma, Melissa J. Green, Laura Ibanez-Gomez, Jakob Grove, Elvira Bramon, Gregory L. Hanna, Cynthia M. Bulik, Yiran Guo, Stephan Ripke, Mary M. Robertson, Harald N. Aschauer, Adebayo Anjorin, Joanna Martin, Bertram Müller-Myhsok, Deborah Kaminská, Jose Guzman-Parra, Benedetta Nacmias, Erik G. Jönsson, Jonathan R. I. Coleman, Douglas F. Levinson, Hamdi Mbarek, Gun Peggy Knudsen, Karin Egberts, Mette Nyegaard, Patrik K. E. Magnusson, Mark Adams, Douglas Blackwood, Elisabeth B. Binder, Marcus Ising, Anna R. Docherty, Jim van Os, Nese Direk, Lina Martinsson, Maria Arranz, Christel M. Middeldorp, Stefan Kloiber, Sintia Iole Belangero, Eske M. Derks, Ingrid Melle, Erlend Bøen, Jan Haavik, Federica Piras, Unna N. Danner, Anil K. Malhotra, Gerome Breen, Stephen V. Faraone, Amanda B Zheutlin, Timothy Poterba, Stephan Ruhrmann, Inge Joa, Ulrik Fredrik Malt, Sarah E. Bergen, Federica Tozzi, Lauren A. Weiss, Hana Papezova, Dominic Holland, Elliot S. Gershon, Jaakko Kaprio, Merete Nordentoft, Scott D. Gordon, Christopher Pittenger, Keun-Ah Cheon, Jennifer Jordan, Philip Gorwood, Myrna M. Weissman, Preben Bo Mortensen, Melissa A. Munn-Chernoff, Isobel Heyman, Eun-Young Shin, Christie L. Burton, Katherine Gordon-Smith, Sietske G. Helder, Peter Nagy, Till F. M. Andlauer, Yunpeng Wang, Young Key Kim, Kate Langley, Søren Dalsgaard, Richard Delorme, Torbjørn Elvsåshagen, Bennett L. Leventhal, Giovanni Gambaro, Christos Androutsos, Jennifer Tübing, Marion Roberts, Annelie Nordin Adolfsson, Hakon Hakonarson, Dorothy E. Grice, Vaughan J. Carr, Konstantinos Tziouvas, Stephanie Zerwas, Cathy L. Barr, Michael Conlon O'Donovan, Per Qvist, Beate St Pourcain, Samuel Kuperman, Leila Karhunen, Jack Samuels, Markus M. Nöthen, Martien J H Kas, Alfonso Tortorella, Mikael Landén, Jennifer Crosbie, Marco A. Grados, Joanna M. Biernacka, Paul D. Arnold, Irene A. Malaty, Jurjen J. Luykx, Nicholas Bass, Naomi R. Wray, Catharina A. Hartman, Christina M. Hultman, Michael S. Okun, Brandon Wormley, Michael Bauer, Daniel J. Smith, Ian Jones, Kathryn Roeder, Brien P. Riley, Caroline M. Nievergelt, Katrin Gade, Sarah Kittel-Schneider, Roy H. Perlis, James R. Mitchell, Ziarih Hawi, James Lee, Liz Forty, William E. Bunney, Thomas Damm Als, Catherine Schaefer, Digby Quested, Matteo Cassina, Anna C. Koller, Patrick Turley, Agnes A. Steixner, Anu Raevuori, Assen Jablensky, Peter Holmans, Dong-Ho Song, S. Evelyn Stewart, Jan K. Buitelaar, Fernando S. Goes, Alexander Münchau, Ayman H. Fanous, Nicolas Ramoz, James B. Potash, Monica Gratacos Mayora, Tobias Banaschewski, Céline S. Reinbold, Renata Rizzo, Arianna Di Florio, Lenka Foretova, Gianfranco Spalletta, Aarno Palotie, Eleftheria Zeggini, Lawrence W. Brown, Julie K. O'Toole, Lynn E. DeLisi, Ulrich Schall, Mary Roberson, Barbara J. Coffey, Bryan J. Mowry, Murray J. Cairns, Dan J. Stein, Glyn Lewis, Marta Ribasés, C. Robert Cloninger, Bettina Konte, John B. Vincent, Duncan S. Palmer, Radhika Kandaswamy, Christine Ladd-Acosta, Lars Alfredsson, Frank Visscher, Ulrike Schmidt, Aiden Corvin, Susan L. Santangelo, Brenda W.J.H. Penninx, David J. Porteous, Tetsuya Ando, Arne E. Vaaler, Bru Cormand, Laura Carlberg, Claire Churchhouse, Manfred Stuhrmann, Niamh Mullins, Christine Søholm Hansen, Cathy L. Budman, Hartmut Imgart, Dan E. Arking, James J. McGough, Michael Gill, Christel Depienne, Roland Burghardt, Antonio Julià, Anders M. Dale, Sven Sandin, Katharina Domschke, Maria Grigoroiu-Serbanescu, Susana Jiménez-Murcia, Marianne Giørtz Pedersen, Zsanett Tarnok, Gisli Baldursson, Michele T. Pato, David M. Hougaard, Thorgeir E. Thorgeirsson, Katharina Bey, Kerstin J. Plessen, Margaret A. Richter, Ole A. Andreassen, Claudine Laurent-Levinson, Leonid Padyukov, Jacques Mallet, Daniela Degortes, John R. Kelsoe, Robert D. Levitan, Andreas Reif, Chaim Huyser, Derek W. Morris, Sina Wanderer, William Byerley, Edna Grünblatt, E.J.C. de Geus, Hyejung Won, Josephine Elia, Rudolf Uher, Jay A. Tischfield, Andreas Karwautz, Gustavo Turecki, Pieter J. Hoekstra, Dorret I. Boomsma, Jacob Rosenthal, Daniele Cusi, Michael C. Neale, Sara Mostafavi, Gwyneth Zai, F. Anthony O'Neill, Gary Donohoe, Karola Rehnström, Harry Brandt, Helena Gaspar, Francis J. McMahon, H-Erich Wichmann, Andrew W. Bergen, Giovanni Coppola, Lea K. Davis, Lenka Slachtova, Olav B. Smeland, Erin C. Dunn, Nicholas G. Martin, Allan L. Naarden, Jo Knight, Cristina Sánchez-Mora, Masashi Ikeda, Lorraine Southam, Sandro Sorbi, Barbara Franke, Martin Schalling, Russell Schachar, Yen-Chen Anne Feng, Kirsten R. Müller-Vahl, André Scherag, Zhaozhong Zhu, Eric A. Storch, Páll Magnússon, David Cohen, Olafur O Gudmundsson, Harvey S. Singer, Brian Kelly, Jonas Bybjerg-Grauholm, Blanca Garcia-Delgar, Thomas Hansen, Carmel M. Loughland, Christine Lochner, Stacy Steinberg, Martin Woods, Jorge A. Quiroz, Raquel Rabionet, Alden Y. Huang, Janice M. Fullerton, María Soler Artigas, Hans J. Grabe, Philip Asherson, Margit Burmeister, Alicia R. Martin, Martin A. Kennedy, Janet Treasure, Anders D. Børglum, Eva C. Schulte, Andreas Hartmann, Frans Henskens, Youl-Ri Kim, Jens Treutlein, Joanna Hauser, Manfred M. Fichter, Damiaan Denys, Ann E. Pulver, Kelly L. 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O., Lucae, S., Maaser, A., Malt, U. F., Martin, N. G., Martinsson, L., Mcelroy, S. L., Mcmahon, F. J., Mcquillin, A., Melle, I., Metspalu, A., Millischer, V., Mitchell, P. B., Montgomery, G. W., Morken, G., Morris, D. W., Muller-Myhsok, B., Mullins, N., Myers, R. M., Nievergelt, C. M., Nordentoft, M., Adolfsson, A. N., Nothen, M. M., Ophoff, R. A., Owen, M. J., Paciga, S. A., Pato, C. N., Pato, M. T., Perlis, R. H., Perry, A., Potash, J. B., Reinbold, C. S., Rietschel, M., Rivera, M., Roberson, M., Schalling, M., Schofield, P. R., Schulze, T. G., Scott, L. J., Serretti, A., Sigurdsson, E., Smeland, O. B., Stordal, E., Streit, F., Strohmaier, J., Thorgeirsson, T. E., Treutlein, J., Turecki, G., Vaaler, A. E., Vieta, E., Vincent, J. B., Wang, Y., Witt, S. H., Zandi, P., Adan, R. A. H., Alfredsson, L., Ando, T., Aschauer, H., Baker, J. H., Bencko, V., Bergen, A. W., Birgegard, A., Perica, V. B., Brandt, H., Burghardt, R., Carlberg, L., Cassina, M., Clementi, M., Courtet, P., Crawford, S., Crow, S., Crowley, J. J., Danner, U. N., Davis, O. S. P., Degortes, D., Desocio, J. E., Dick, D. M., Dina, C., Docampo, E., Egberts, K., Ehrlich, S., Espeseth, T., Fernandez-Aranda, F., Fichter, M. M., Foretova, L., Forzan, M., Gambaro, G., Giegling, I., Gonidakis, F., Gorwood, P., Mayora, M. G., Guo, Y., Halmi, K. A., Hatzikotoulas, K., Hebebrand, J., Helder, S. G., Herpertz-Dahlmann, B., Herzog, W., Hinney, A., Imgart, H., Jimenez-Murcia, S., Johnson, C., Jordan, J., Julia, A., Kaminska, D., Karhunen, L., Karwautz, A., Kas, M. J. H., Kaye, W. H., Kennedy, M. A., Kim, Y. -R., Klareskog, L., Klump, K. L., Knudsen, G. P. S., Landen, M., Le Hellard, S., Levitan, R. D., Li, D., Lichtenstein, P., Maj, M., Marsal, S., Mcdevitt, S., Mitchell, J., Monteleone, P., Monteleone, A. M., Munn-Chernoff, M. A., Nacmias, B., Navratilova, M., O'Toole, J. K., Padyukov, L., Pantel, J., Papezova, H., Rabionet, R., Raevuori, A., Ramoz, N., Reichborn-Kjennerud, T., Ricca, V., Roberts, M., Rujescu, D., Rybakowski, F., Scherag, A., Schmidt, U., Seitz, J., Slachtova, L., Slof-Op't Landt, M. C. T., Slopien, A., Sorbi, S., Southam, L., Strober, M., Tortorella, A., Tozzi, F., Treasure, J., Tziouvas, K., van Elburg, A. A., Wade, T. D., Wagner, G., Walton, E., Watson, H. J., Wichmann, H. -E., Woodside, D. B., Zeggini, E., Zerwas, S., Zipfel, S., Adams, M. J., Andlauer, T. F. M., Berger, K., Binder, E. B., Boomsma, D. I., Castelao, E., Colodro-Conde, L., Direk, N., Docherty, A. R., Domenici, E., Domschke, K., Dunn, E. C., Foo, J. C., D, e. Geus E. J. C., Grabe, H. J., Hamilton, S. P., Horn, C., Hottenga, J. -J., Howard, D., Ising, M., Kloiber, S., Levinson, D. F., Lewis, G., Magnusson, P. K. E., Mbarek, H., Middeldorp, C. M., Mostafavi, S., Nyholt, D. R., Penninx, B. W., Peterson, R. E., Pistis, G., Porteous, D. J., Preisig, M., Quiroz, J. A., Schaefer, C., Schulte, E. C., Shi, J., Smith, D. J., Thomson, P. A., Tiemeier, H., Uher, R., van der Auwera, S., Weissman, M. M., Alexander, M., Begemann, M., Bramon, E., Buccola, N. G., Cairns, M. J., Campion, D., Carr, V. J., Cloninger, C. R., Cohen, D., Collier, D. A., Corvin, A., Delisi, L. E., Donohoe, G., Dudbridge, F., Duan, J., Freedman, R., Gejman, P. V., Golimbet, V., Godard, S., Ehrenreich, H., Hartmann, A. M., Henskens, F. A., Ikeda, M., Iwata, N., Jablensky, A. V., Joa, I., Jonsson, E. G., Kelly, B. J., Knight, J., Konte, B., Laurent-Levinson, C., Lee, J., Lencz, T., Lerer, B., Loughland, C. M., Malhotra, A. K., Mallet, J., Mcdonald, C., Mitjans, M., Mowry, B. J., Murphy, K. C., Murray, R. M., O'Neill, F. A., Oh, S. -Y., Palotie, A., Pantelis, C., Pulver, A. E., Petryshen, T. L., Quested, D. J., Riley, B., Sanders, A. R., Schall, U., Schwab, S. G., Scott, R. J., Sham, P. C., Silverman, J. M., Sim, K., Steixner, A. A., Tooney, P. A., van Os, J., Vawter, M. P., Walsh, D., Weiser, M., Wildenauer, D. B., Williams, N. M., Wormley, B. K., Zhang, F., Androutsos, C., Arnold, P. D., Barr, C. L., Barta, C., Bey, K., Bienvenu, O. J., Black, D. W., Brown, L. W., Budman, C., Cath, D., Cheon, K. -A., Ciullo, V., Coffey, B. J., Cusi, D., Davis, L. K., Denys, D., Depienne, C., Dietrich, A., Eapen, V., Falkai, P., Fernandez, T. V., Garcia-Delgar, B., Geller, D. A., Gilbert, D. L., Grados, M. A., Greenberg, E., Grunblatt, E., Hagstrom, J., Hanna, G. L., Hartmann, A., Hedderly, T., Heiman, G. A., Heyman, I., Hong, H. J., Huang, A., Huyser, C., Ibanez-Gomez, L., Khramtsova, E. A., Kim, Y. K., Kim, Y. -S., King, R. A., Koh, Y. -J., Konstantinidis, A., Kook, S., Kuperman, S., Leventhal, B. L., Lochner, C., Ludolph, A. G., Madruga-Garrido, M., Malaty, I., Maras, A., Mccracken, J. T., Meijer, I. A., Mir, P., Morer, A., Muller-Vahl, K. R., Munchau, A., Murphy, T. L., Naarden, A., Nagy, P., Nestadt, G., Nestadt, P. S., Nicolini, H., Nurmi, E. L., Okun, M. S., Paschou, P., Piras, F., Pittenger, C., Plessen, K. J., Richter, M. A., Rizzo, R., Robertson, M., Roessner, V., Ruhrmann, S., Samuels, J. F., Sandor, P., Schlogelhofer, M., Shin, E. -Y., Singer, H., Song, D. -H., Song, J., Spalletta, G., Stein, D. J., Stewart, S. E., Storch, E. A., Stranger, B., Stuhrmann, M., Tarnok, Z., Tischfield, J. A., Tubing, J., Visscher, F., Vulink, N., Wagner, M., Walitza, S., Wanderer, S., Woods, M., Worbe, Y., Zai, G., Zinner, S. H., Sullivan, P. F., Franke, B., Daly, M. J., Bulik, C. M., Mcintosh, A. M., O'Donovan, M. C., Zheutlin, A., Andreassen, O. A., Borglum, A. D., Breen, G., Edenberg, H. J., Fanous, A. H., Faraone, S. V., Gelernter, J., Mathews, C. A., Mattheisen, M., Mitchell, K. S., Neale, M. C., Nurnberger, J. I., Ripke, S., Santangelo, S. L., Scharf, J. M., Stein, M. B., Thornton, L. M., Walters, J. T. R., Wray, N. R., Geschwind, D. H., Neale, B. M., Kendler, K. S., and Smoller, J. W.

Subjects
Netherlands Twin Register (NTR), cross-disorder genetics, Medizin, Genome-wide association study, Tourette syndrome, functional genomics, gene expression, genetic architecture, genetic correlation, GWAS, neurodevelopment, pleiotropy, psychiatric disorders, Psychiatric genetics, 0302 clinical medicine, Pleiotropy, functional genomic, WIDE ASSOCIATION, cross-disorder genetic, 0303 health sciences, Mental Disorders, Genetic Pleiotropy, HUMAN BRAIN, INSIGHTS, Autism spectrum disorder, Schizophrenia, DISEASES, GENETIC CORRELATIONS, medicine.medical_specialty, Neurogenesis, Quantitative Trait Loci, BF, Biology, GENOTYPE IMPUTATION, Psychiatric geneticscross-disorder geneticspsychiatric disorderspleiotropyneurodevelopmentGWASgenetic correlationgene expressiongenetic architecturefunctional genomics, Article, General Biochemistry, Genetics and Molecular Biology, psychiatric disorder, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, Humans, Genetic Predisposition to Disease, Bipolar disorder, TRANSCRIPTOME, Psychiatry, 030304 developmental biology, Gwas, Psychiatric Genetics, Cross-disorder Genetics, Functional Genomics, Gene Expression, Genetic Architecture, Genetic Correlation, Neurodevelopment, Psychiatric Disorders, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], IDENTIFICATION, MUTATIONS, medicine.disease, Genetic architecture, DEMETHYLASE, RC0321, 1182 Biochemistry, cell and molecular biology, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.

Published
2019

20. Comorbidities, Social Impact, and Quality of Life in Tourette Syndrome

Author

Andrea E. Cavanna, Valsamma Eapen, Mary M. Robertson, Eapen, V, Cavanna, A, and Robertson, M

Subjects
psychosocial, medicine.medical_specialty, Attention Deficit Hyperactivity Disorder, Tics, lcsh:RC435-571, Population, autism spectrum disorder, Tourette syndrome, 03 medical and health sciences, 0302 clinical medicine, lcsh:Psychiatry, attention-deficit hyperactivity disorder, obsessive compulsive disorder, mental disorders, medicine, Attention deficit hyperactivity disorder, co-morbidity, Psychiatry, education, Obsessive-compulsive disorder (OCD), education.field_of_study, medicine.disease, psychopathology, Autism spectrum disorders (ASD), 030227 psychiatry, Psychiatry and Mental health, comorbidity, quality of life, Autism spectrum disorder, Perspective, Anxiety, medicine.symptom, Psychology, Psychosocial, 030217 neurology & neurosurgery, Clinical psychology
Abstract

Tourette Syndrome (TS) is more than having motor and vocal tics, and this review will examine the varied co-morbidities as well as the social impact and Quality of Life (QoL) in individuals with TS. The relationship between any individual and his/her environment is complex and this is further exaggerated in the case of a person with TS. For example, tics may play a significant role in shaping the person’s experiences, perceptions and interactions with the environment. Further, associated clinical features, co-morbidities and co-existing psychopathologies may compound or alter this relationship. The common co-morbidities in this regard include Attention Deficit Hyperactivity Disorder (ADHD) and disruptive behaviours, Obsessive Compulsive Disorder (OCD) and Autism Spectrum Disorder (ASD), and co-existent problems include anxiety, depression and low self esteem, which can all lead to poorer psychosocial functioning and QoL. Thus, the symptoms of TS and the associated co-morbid conditions may interact to result in a vicious cycle or a downward spiralling of negative experiences and poor QoL. The stigma and social maladjustment in TS and the social exclusion, bullying and discrimination is considered to be caused in large part by misperceptions of the disorder by teachers, peers, and the wider community. Improved community and professional awareness about TS and related co-morbidities & other psychopathologies as well as the provision of multidisciplinary services to meet the complex needs of this clinical population are critical. Future research to inform the risk and resilience factors for successful long term outcomes is also warranted.

Published
2016

21. Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD

Author

Mary M. Robertson, Peter Heutink, Leonhard Lennertz, Victor I. Reus, John Hardy, Mark A. Riddle, Beatriz Camarena, Helena Garrido, Robert A. King, Simon Girard, Christine Lochner, Michael H. Bloch, Patrick Evans, Anuar Konkashbaev, Jack Samuels, Priya Moorjani, Chiara Sabatti, Andrew J. Pakstis, Ying Wang, O. Joseph Bienvenu, Richard Delorme, David L. Pauls, Rainald Moessner, Gary A. Heiman, Daniel A. Geller, Marco A. Grados, Eric R. Gamazon, John Piacentini, Dan J. Stein, William Cornejo Ochoa, Maria Conceição do Rosário, Karin Egberts, Thomas L. Lowe, Christopher K. Edlund, Jan Smit, Christopher Pittenger, Denise A. Chavira, Marion Leboyer, Homero Vallada, Sandra Catalina Mesa Restrepo, Jacquelyn Crane, Donald W. Black, David V. Conti, Paul Sandor, Humberto Nicolini, Lisa Osiecki, Jeremy Veenstra-VanderWeele, Catherine Mayerfeld, Danielle Posthuma, Edna Grünblatt, Carolina Cappi, Robert B. Weiss, Cristina Barlassina, Sara Lupoli, Chunyu Liu, Sian M. J. Hemmings, Ben A. Oostra, D. Denys, Susanne Walitza, Lea K. Davis, Stephen A. Haddad, Luis Diego Herrera, Jubel Morgan, Hans Joergen Grabe, Benjamin M. Neale, Thomas V. Fernandez, Yehuda Pollak, Roel A. Ophoff, Gerald Nestadt, Harvey S. Singer, Stephan Ruhrmann, Bernadette Cullen, Michael Wagner, Nuria Lanzagorta, Jeremiah M. Scharf, Cathy L. Budman, Ruth D. Bruun, R. Kurlan, Valsama Eapen, Jesen Fagerness, Desmond Campbell, James L. Kennedy, Carlos N. Pato, Nancy J. Cox, Pieter J. Hoekstra, Joseph Jankovic, Cathy L. Barr, Peter Falkai, Donald L. Gilbert, Fortu Benarroch, Dianne M. Hezel, Maria Cristina Cavallini, Brooke Sheppard, Fabio Macciardi, William M. McMahon, Laura Bellodi, Maurizio Turiel, Wolfgang Maier, Varda Gross-Tsur, Helena Brentani, Dongmei Yu, Danielle C. Cath, Ana V. Valencia Duarte, Eduardo Fournier, James A. Knowles, Tobias J. Renner, Erika L. Nurmi, Guy A. Rouleau, Benjamin D. Greenberg, Nelson B. Freimer, Shaun Purcell, Patience J. Gallagher, Roxana Romero, Gregory L. Hanna, Paolo Manunta, Edwin H. Cook, Michele T. Pato, Sylvain Chouinard, Scott L. Rauch, James T. McCracken, Gloria Gerber, Carol A. Mathews, Jens R. Wendland, Sampath Arepalli, Dennis L. Murphy, Daniele Cusi, Barbara Kremeyer, Vladimir Coric, Aline S. Sampaio, Erika Salvi, Julio C. Cardona Silgado, Cornelia Illmann, James F. Leckman, Euripedes Constantino Miguel, H. Müller, Yin Yao Shugart, Eric Strengman, Ana Gabriela Hounie, Michael E. Weale, Gabriel Bedoya Berrió, Margaret A. Richter, Maurizio Marconi, Allan L. Naarden, Michael A. Jenike, M.R. Cookson, David R. Rosenberg, Andres Ruiz-Linares, S. Evelyn Stewart, Paul D. Arnold, H.G.M. Westenberg, Yves Dion, Jay A. Tischfield, Eske M. Derks, Lauren M. McGrath, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Yu, D., Mathews, C. A., Scharf, J. M., Neale, B. M., Davis, L. K., Gamazon, E. R., Derks, E. M., Evans, P., Edlund, C. K., Crane, J., Fagerness, J. A., Osiecki, L., Gallagher, P., Gerber, G., Haddad, S., Illmann, C., Mcgrath, L. M., Mayerfeld, C., Arepalli, S., Barlassina, C., Barr, C. L., Bellodi, L., Benarroch, F., Berrio, G. B., Bienvenu, O. J., Black, D., Bloch, M. H., Brentani, H., Bruun, R. D., Budman, C. L., Camarena, B., Campbell, D. D., Cappi, C., Cardona Silgado, J. C., Cavallini, M. C., Chavira, D. A., Chouinard, S., Cook, E. H., Cookson, M. R., Coric, V., Cullen, B., Cusi, D., Delorme, R., Denys, D., Dion, Y., Eapen, V., Egberts, K., Falkai, P., Fernandez, T., Fournier, E., Garrido, H., Geller, D., Gilbert, D., Girard, S. L., Grabe, H. J., Grados, M. A., Greenberg, B. D., Gross-Tsur, V., Grunblatt, E., Hardy, J., Heiman, G. A., Hemmings, S. M. J., Herrera, L. D., Hezel, D. M., Hoekstra, P. J., Jankovic, J., Kennedy, J. L., King, R. A., Konkashbaev, A. I., Kremeyer, B., Kurlan, R., Lanzagorta, N., Leboyer, M., Leckman, J. F., Lennertz, L., Liu, C., Lochner, C., Lowe, T. L., Lupoli, S., Macciardi, F., Maier, W., Manunta, P., Marconi, M., Mccracken, J. T., Mesa Restrepo, S. C., Moessner, R., Moorjani, P., Morgan, J., Muller, H., Murphy, D. L., Naarden, A. L., Ochoa, W. C., Ophoff, R. A., Pakstis, A. J., Pato, M. T., Pato, C. N., Piacentini, J., Pittenger, C., Pollak, Y., Rauch, S. L., Renner, T., Reus, V. I., Richter, M. A., Riddle, M. A., Robertson, M. M., Romero, R., Rosario, M. C., Rosenberg, D., Ruhrmann, S., Sabatti, C., Salvi, E., Sampaio, A. S., Samuels, J., Sandor, P., Service, S. K., Sheppard, B., Singer, H. S., Smit, J. H., Stein, D. J., Strengman, E., Tischfield, J. A., Turiel, M., Valencia Duarte, A. V., Vallada, H., Veenstra-VanderWeele, J., Walitza, S., Walkup, J., Wang, Y., Weale, M., Weiss, R., Wendland, J. R., Westenberg, H. G. M., Yao, Y., Hounie, A. G., Miguel, E. C., Nicolini, H., Wagner, M., Ruiz-Linares, A., Cath, D. C., Mcmahon, W., Posthuma, D., Oostra, B. A., Nestadt, G., Rouleau, G. A., Purcell, S., Jenike, M. A., Heutink, P., Hanna, G. L., Conti, D. V., Arnold, P. D., Freimer, N., Stewart, S. E., Knowles, J. A., Cox, N. J., Pauls, D. L., Netherlands Institute for Neuroscience (NIN), Sub String Theory Cosmology and ElemPart, Leerstoel Hout, Experimental psychopathology, Psychiatry, Human genetics, NCA - Neurobiology of mental health, EMGO - Mental health, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Other departments, ANS - Amsterdam Neuroscience, APH - Amsterdam Public Health, Adult Psychiatry, Complex Trait Genetics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, and EMGO+ - Mental Health

Subjects
Adult, Male, Obsessive-Compulsive Disorder, diagnosis [Tourette Syndrome], Tics, Single-nucleotide polymorphism, Genome-wide association study, Comorbidity, VARIANTS, Tourette syndrome, Polymorphism, Single Nucleotide, Severity of Illness Index, ASSOCIATION SCANS, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Polymorphism (computer science), Severity of illness, mental disorders, medicine, TICS, Humans, ddc:610, Polymorphism, 030304 developmental biology, Genetics, Psychiatric Status Rating Scales, genetics [Obsessive-Compulsive Disorder], 0303 health sciences, GENERALIST GENES, Single Nucleotide, OBSESSIVE-COMPULSIVE DISORDER, epidemiology [Tourette Syndrome], medicine.disease, Genetic architecture, Psychiatry and Mental health, genetics [Tourette Syndrome], Female, epidemiology [Obsessive-Compulsive Disorder], Psychology, 030217 neurology & neurosurgery, diagnosis [Obsessive-Compulsive Disorder], Genome-Wide Association Study, Tourette Syndrome
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=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.

Published
2015

22. Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study

Author

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, Leerstoel Hout, Sub String Theory Cosmology and ElemPart, Experimental psychopathology, University of Zurich, Scharf, Jeremiah M, Leerstoel Hout, Sub String Theory Cosmology and ElemPart, Experimental psychopathology, Clinical Genetics, Child and Adolescent Psychiatry / Psychology, Artificial intelligence, Complex Trait Genetics, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Functional Genomics, AIMMS, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, ANS - Amsterdam Neuroscience, Adult Psychiatry, APH - Amsterdam Public Health, Netherlands Institute for Neuroscience (NIN), Mcgrath, Lm, Yu, D, Marshall, C, Davis, Lk, Thiruvahindrapuram, B, Li, B, Cappi, C, Gerber, G, Wolf, A, Schroeder, Fa, Osiecki, L, O'Dushlaine, C, Kirby, A, Illmann, C, Haddad, S, Gallagher, P, Fagerness, Ja, Barr, Cl, Bellodi, Laura, Benarroch, F, Bienvenu, Oj, Black, Dw, Bloch, Mh, Bruun, Rd, Budman, Cl, Camarena, B, Cath, Dc, Cavallini, Mc, Chouinard, S, Coric, V, Cullen, B, Delorme, R, Denys, D, Derks, Em, Dion, Y, Rosário, Mc, Eapen, V, Evans, P, Falkai, P, Fernandez, Tv, Garrido, H, Geller, D, Grabe, Hj, Grados, Ma, Greenberg, Bd, Gross Tsur, V, Grünblatt, E, Heiman, Ga, Hemmings, Sm, Herrera, Ld, Hounie, Ag, Jankovic, J, Kennedy, Jl, King, Ra, Kurlan, R, Lanzagorta, N, Leboyer, M, Leckman, Jf, Lennertz, L, Lochner, C, Lowe, Tl, Lyon, Gj, Macciardi, F, Maier, W, Mccracken, Jt, Mcmahon, W, Murphy, Dl, Naarden, Al, Neale, Bm, Nurmi, E, Pakstis, Aj, Pato, Mt, Pato, Cn, Piacentini, J, Pittenger, C, Pollak, Y, Reus, Vi, Richter, Ma, Riddle, M, Robertson, Mm, Rosenberg, D, Rouleau, Ga, Ruhrmann, S, Sampaio, A, Samuels, J, Sandor, P, Sheppard, B, Singer, H, Smit, Jh, Stein, Dj, Tischfield, Ja, Vallada, H, Veenstra VanderWeele, J, Walitza, S, Wang, Y, Wendland, Jr, Shugart, Yy, Miguel, Ec, Nicolini, H, Oostra, Ba, Moessner, R, Wagner, M, Ruiz Linares, A, Heutink, P, Nestadt, G, Freimer, N, Petryshen, T, Posthuma, D, Jenike, Ma, Cox, Nj, Hanna, Gl, Brentani, H, Scherer, Sw, Arnold, Pd, Stewart, Se, Mathews, Ca, Knowles, Ja, Cook, Eh, Pauls, Dl, Wang, K, Scharf, J. M., Psychiatry, Human genetics, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, and EMGO - Mental health

Subjects
Oncology, Male, medicine.medical_specialty, diagnosis [Tourette Syndrome], Adolescent, DNA Copy Number Variations, Genome-wide association study, 610 Medicine & health, Tourette syndrome, Polymorphism, Single Nucleotide, behavioral disciplines and activities, Article, 2738 Psychiatry and Mental Health, SDG 3 - Good Health and Well-being, Obsessive compulsive, Genetic etiology, Internal medicine, mental disorders, Developmental and Educational Psychology, medicine, Humans, Genetic Predisposition to Disease, genetics, Copy-number variation, ddc:610, Genetics, genetics [Obsessive-Compulsive Disorder], 3204 Developmental and Educational Psychology, copy number variation, 10058 Department of Child and Adolescent Psychiatry, medicine.disease, 16p13.11, Diagnostic and Statistical Manual of Mental Disorders, obsessive-compulsive disorder, Psychiatry and Mental health, genetics [Tourette Syndrome], Schizophrenia, Autism, Female, Psychology, Genome-Wide Association Study, diagnosis [Obsessive-Compulsive Disorder]
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 (

Published
2014

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