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1. A parietal biomarker for ADHD liability:As predicted by The Distributed Effects Perspective Model of ADHD

Author

T. Sigi eHale, Joshua F. Wiley, Susan L. Smalley, Kelly L. Tung, Olivia eKaminsky, James J. McGough, Ashwin M. Jaini, and Sandra K. Loo

Subjects
Anxiety, Attention, Cognition, Depression, asymmetry, EEG, Psychiatry, RC435-571
Abstract

Background: We previously hypothesized that poor task-directed sensory information processing should be indexed by increased weighting of right hemisphere (RH) biased attention and visuo-perceptual brain functions during task operations, and have demonstrated this phenotype in ADHD across multiple studies, using multiple methodologies. However, in our recent Distributed Effects Model of ADHD, we surmised that this phenotype is not ADHD specific, but rather more broadly reflective of any circumstance that disrupts the induction and maintenance of an emergent task-directed neural architecture. Under this view, increased weighting of RH biased attention and visuo-perceptual brain functions is expected to generally index neurocognitive sets that are not optimized for task-directed thought and action, and when durable expressed, liability for ADHD. Method: The current study tested this view by examining whether previously identified rightward parietal EEG asymmetry in ADHD was associated with common ADHD characteristics and comorbidities (i.e., ADHD risk factors). Results: Barring one exception (non-right handedness), we found that it was. Rightward parietal asymmetry was associated with carrying the DRD4-7R risk allele, being male, having mood disorder, and having anxiety disorder. However, differences in the specific expression of rightward parietal asymmetry were observed, which are discussed in relation to possible unique mechanisms underlying ADHD liability in different ADHD RFs. Conclusion: Rightward parietal asymmetry appears to be a durable feature of ADHD liability, as predicted by the Distributed Effects Perspective Model of ADHD. Moreover, variability in the expression of this phenotype may shed light on different sources of ADHD liability.

Published
2015
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2. Fully Present : The Science, Art, and Practice of Mindfulness

Author

Susan L. Smalley, Diana Winston, Susan L. Smalley, and Diana Winston

Subjects
Mental healing, Meditation
Abstract

“Excellent. Fully Present offers one of the clearest introductions to mindfulness in the field.” —Library Journal Mindfulness has attracted ever‑growing interest and tens of thousands of practitioners, who have come to the discipline from both within and outside the Buddhist tradition. In Fully Present, leading mindfulness researchers and educators Dr. Sue Smalley and Diana Winston provide an all‑in‑one guide for anyone interested in bringing mindfulness to daily life as a means of enhancing well‑being. This new edition, how with a new afterword, provides both a scientific explanation for how mindfulness positively and powerfully affects the brain and the body as well as practical guidance to develop both a practice and mindfulness in daily living, not only through meditation but also during daily experiences. Now, you can wait in line at the supermarket, exercise, or face difficult news with calm and mental fortitude. Ditch the absent-minded lifestyle and begin bringing your full self and your full mind everywhere. With research studies, personal accounts, and practical applications, Fully Present highlights how things like simply breathing, listening, and walking can change your perspective--and your life.

Published
2022

3. Parsing heterogeneity in attention‐deficit hyperactivity disorder using <scp>EEG</scp> ‐based subgroups

Author

James T. McCracken, James J. McGough, Sandra K. Loo, and Susan L. Smalley

Subjects
Male, medicine.medical_specialty, Adolescent, Child Behavior, Behavioral Symptoms, Audiology, Electroencephalography, Article, Developmental psychology, 03 medical and health sciences, 0302 clinical medicine, Rating scale, Developmental and Educational Psychology, medicine, Humans, Attention deficit hyperactivity disorder, Cognitive Dysfunction, 0501 psychology and cognitive sciences, Affective Symptoms, Cognitive skill, Child, Resting state fMRI, medicine.diagnostic_test, 05 social sciences, Cognition, medicine.disease, Brain Waves, Latent class model, Cognitive test, Psychiatry and Mental health, Adolescent Behavior, Attention Deficit Disorder with Hyperactivity, Pediatrics, Perinatology and Child Health, Female, Psychology, 030217 neurology & neurosurgery, 050104 developmental & child psychology
Abstract

Background Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous condition for which multiple efforts to characterize brain state differences are underway. The objective of this study was to identify distinct subgroups of resting electroencephalography (EEG) profiles among children with and without ADHD and subsequently provide extensive clinical characterization of the subgroups. Methods Latent class analysis was used with resting state EEG recorded from a large sample of 781 children with and without ADHD (N = 620 ADHD, N = 161 Control), aged 6–18 years old. Behavioral and cognitive characteristics of the latent classes were derived from semistructured diagnostic interviews, parent completed behavior rating scales, and cognitive test performance. Results A five-class solution was the best fit for the data, of which four classes had a defining spectral power elevation. The distribution of ADHD and control subjects was similar across classes suggesting there is no one resting state EEG profile for children with or without ADHD. Specific latent classes demonstrated distinct behavioral and cognitive profiles. Those with elevated slow-wave activity (i.e. delta and theta band) had higher levels of externalizing behaviors and cognitive deficits. Latent subgroups with elevated alpha and beta power had higher levels of internalizing behaviors, emotion dysregulation, and intact cognitive functioning. Conclusions There is population-level heterogeneity in resting state EEG subgroups, which are associated with distinct behavioral and cognitive profiles. EEG measures may be more useful biomarkers of ADHD outcome or treatment response rather than diagnosis.

Published
2017

4. Characterizing Emotional State Transitions During Prolonged Use of a Mindfulness and Meditation App: Observational Study

Author

Julie Campistron, Susan L. Smalley, Nick Bender, Jamie Price, Argus J Athanas, Jamison McCorrison, and Nicholas J. Schork

Subjects
mindfulness, Mindfulness, media_common.quotation_subject, Applied psychology, Psychological intervention, smartphone, 03 medical and health sciences, emotional distress, 0302 clinical medicine, Psychology, Meditation, media_common, mobile apps, Original Paper, mobile phone, Transition (fiction), Mental health, BF1-990, 030227 psychiatry, Psychiatry and Mental health, Mood, Mobile phone, Observational study, mental health, 030217 neurology & neurosurgery
Abstract

Background The increasing demand for mental health care, a lack of mental health care providers, and unequal access to mental health care services have created a need for innovative approaches to mental health care. Digital device apps, including digital therapeutics, that provide recommendations and feedback for dealing with stress, depression, and other mental health issues can be used to adjust mood and ultimately show promise to help meet this demand. In addition, the recommendations delivered through such apps can also be tailored to an individual’s needs (ie, personalized) and thereby potentially provide greater benefits than traditional “one-size-fits-all” recommendations. Objective This study aims to characterize individual transitions from one emotional state to another during the prolonged use of a digital app designed to provide a user with guided meditations based on their initial, potentially negative, emotional state. Understanding the factors that mediate such transitions can lead to improved recommendations for specific mindfulness and meditation interventions or activities (MMAs) provided in mental health apps. Methods We analyzed data collected during the use of the Stop, Breathe & Think (SBT) mindfulness app. The SBT app prompts users to input their emotional state before and immediately after engaging with MMAs recommended by the app. Data were collected from more than 650,000 SBT users engaging in nearly 5 million MMAs. We limited the scope of our analysis to users with 10 or more MMA sessions that included at least 6 basal emotional state evaluations. Using clustering techniques, we grouped emotions recorded by individual users and then applied longitudinal mixed effect models to assess the associations between individual recommended MMAs and transitions from one group of emotions to another. Results We found that basal emotional states have a strong influence on transitions from one emotional state to another after MMA engagement. We also found that different MMAs impact these transitions, and many were effective in eliciting a healthy transition but only under certain conditions. In addition, we observed gender and age effects on these transitions. Conclusions We found that the initial emotional state of an SBT app user determines the type of SBT MMAs that will have a favorable effect on their transition from one emotional state to another. Our results have implications for the design and use of guided mental health recommendations for digital device apps.

Published
2021

5. Association Between Improvement in Baseline Mood and Long-Term Use of a Mindfulness and Meditation App: Observational Study

Author

Paul Wehner, Nicholas J. Schork, Susan L. Smalley, Julie Campistron, Jamison McCorrison, Jim Grady, Argus J Athanas, and Jamie Price

Subjects
Guided meditation, Mediation (statistics), mindfulness, Mindfulness, 020205 medical informatics, media_common.quotation_subject, Psychological intervention, 02 engineering and technology, smartphone, 03 medical and health sciences, 0302 clinical medicine, mental disorders, 0202 electrical engineering, electronic engineering, information engineering, 030212 general & internal medicine, Meditation, media_common, Original Paper, emotional well-being, Corrigenda and Addenda, Mental health, Emotional well-being, Psychiatry and Mental health, Mood, Psychology, mental health, Clinical psychology
Abstract

Background The use of smartphone apps to monitor and deliver health care guidance and interventions has received considerable attention recently, particularly with regard to behavioral disorders, stress relief, negative emotional state, and poor mood in general. Unfortunately, there is little research investigating the long-term and repeated effects of apps meant to impact mood and emotional state. Objective We aimed to investigate the effects of both immediate point-of-intervention and long-term use (ie, at least 10 engagements) of a guided meditation and mindfulness smartphone app on users’ emotional states. Data were collected from users of a mobile phone app developed by the company Stop, Breathe & Think (SBT) for achieving emotional wellness. To explore the long-term effects, we assessed changes in the users’ basal emotional state before they completed an activity (eg, a guided meditation). We also assessed the immediate effects of the app on users’ emotional states from preactivity to postactivity. Methods The SBT app collects information on the emotional state of the user before and after engagement in one or several mediation and mindfulness activities. These activities are recommended and provided by the app based on user input. We considered data on over 120,000 users of the app who collectively engaged in over 5.5 million sessions with the app during an approximate 2-year period. We focused our analysis on users who had at least 10 engagements with the app over an average of 6 months. We explored the changes in the emotional well-being of individuals with different emotional states at the time of their initial engagement with the app using mixed-effects models. In the process, we compared 2 different methods of classifying emotional states: (1) an expert-defined a priori mood classification and (2) an empirically driven cluster-based classification. Results We found that among long-term users of the app, there was an association between the length of use and a positive change in basal emotional state (4% positive mood increase on a 2-point scale every 10 sessions). We also found that individuals who were anxious or depressed tended to have a favorable long-term emotional transition (eg, from a sad emotional state to a happier emotional state) after using the app for an extended period (the odds ratio for achieving a positive emotional state was 3.2 and 6.2 for anxious and depressed individuals, respectively, compared with users with fewer sessions). Conclusions Our analyses provide evidence for an association between both immediate and long-term use of an app providing guided meditations and improvements in the emotional state.

Published
2019

6. Characterization of the Theta to Beta Ratio in ADHD

Author

James T. McCracken, Susan L. Smalley, Alexander L. Cho, James J. McGough, Sandra K. Loo, and T. Sigi Hale

Subjects
Adult, Conduct Disorder, medicine.medical_specialty, Bipolar Disorder, Adolescent, Comorbidity, Electroencephalography, behavioral disciplines and activities, Reference Values, mental disorders, Developmental and Educational Psychology, medicine, Humans, Attention deficit hyperactivity disorder, Theta Rhythm, Child, Psychiatry, Depression (differential diagnoses), Cerebral Cortex, Depressive Disorder, Major, Intelligence quotient, medicine.diagnostic_test, Age Factors, Signal Processing, Computer-Assisted, Cognition, Middle Aged, Prognosis, medicine.disease, Cognitive test, Clinical Psychology, Attention Deficit Disorder with Hyperactivity, Attention Deficit and Disruptive Behavior Disorders, Child, Preschool, Anxiety, Dysthymic Disorder, medicine.symptom, Beta Rhythm, Cognition Disorders, Psychology, Clinical psychology
Abstract

Objective: The goal of this study is to characterize the theta to beta ratio (THBR) obtained from electroencephalogram (EEG) measures, in a large sample of community and clinical participants with regard to (a) ADHD diagnosis and subtypes, (b) common psychiatric comorbidities, and (c) cognitive correlates. Method: The sample includes 871 participants (595 youth and 276 adults) with and without ADHD. All participants underwent extensive assessment, including semistructured diagnostic interviews, cognitive testing, and EEG recording. Results: The THBR did not differ significantly by ADHD status for youth but was significantly lower in adults with ADHD compared with controls. ADHD subtype and psychiatric comorbidities such as disruptive behavior disorders and depression have opposing and significant mediating effects on the THBR. Conclusion: The THBR is affected by several mediating factors associated with ADHD such as ADHD subtype and psychiatric comorbidity. More research is needed to understand the functional significance of the THBR in ADHD.

Published
2012

7. Further characterization of the autism susceptibility locus AUTS1 on chromosome 7q

Author

Angela J. Marlow, Anthony Cox, Andrew Pickles, Patrick Bolton, Elaine Thompson, Lisa Chrzanowski, Pat Scudder, Kim S. Beyer, Jeanne Fremolle-Kruck, Ros Packer, Anthony P. Monaco, Annemarie Poustka, Janine Michelotti, Axel Benner, Karen Brøndum-Nielsen, Michael Rutter, Christina Corsello, Elizabeth P. Green, Tom Berney, Jane Whittacker, Fred R. Volkmar, Bennett L. Leventhal, Catherine Wainhouse, Simon Wallace, Maretha de Jonge, Elena Maestrini, Sabine M. Klauck, Claire Garner, Catherine Pienkowski, Ramyani Gupta, Alina Paul, David L. Pauls, Chantal Kemner, Edwin H. Cook, Katerina Papanikolaou, Marie Thérèse Tauber, Eric Fombonne, Pamela Warburton, Catherine Lord, Lennart Pedersen, Jonathan Green, Thomas Kelly, Amaia Hervas, Bernadette Rogé, Helen McConachie, Sabine Feineis-Matthews, Sabine Epp, Gillian Baird, Anne Aubin, Rodney M. J. Cotterill, Fritz Poustka, Janette Moore, Amy Liu, Martha Turner, Daniel E. Weeks, Janine A. Lamb, Julia Bailey, Martha Dedricks, John Tsiantis, Sven Bölte, Jennifer G. Levitt, Sarah Palferman, Gabriele Schmötzer, Nicola Matthews, Zoe Docherty, Gabrielle Barnby, Stephen Abbs, Susan L. Smalley, Bryan Bolton, Ann Le Couteur, Marianne Murin, Herman van Engeland, Dorothea Rühl, Petrus J. de Vries, Stephen J. Guter, Anthony J. Bailey, Demetrious Haracopos, Gunna Eriksen, and Anne Gilchrist

Subjects
Genetic Markers, Male, Linkage disequilibrium, Genotype, Genetic Linkage, Biology, Polymerase Chain Reaction, Neurodevelopmental disorder, Genetic linkage, Genetics, medicine, Genetic predisposition, Chromosomes, Human, Humans, Allele, Autistic Disorder, Molecular Biology, Genetics (clinical), Alleles, Linkage (software), Linkage Disequilibrium Mapping, Chromosome Mapping, General Medicine, medicine.disease, Genetic marker, Female, Disease Susceptibility, Chromosomes, Human, Pair 7
Abstract

Autism is a neurodevelopmental disorder that usually arises on the basis of a complex genetic predisposition. The most significant susceptibility region in the first whole genome screen of multiplex families was on chromosome 7q, although this linkage was evident only in UK IMGSAC families. Subsequently all other genome screens of non-UK families have found some evidence of increased allele sharing in an overlapping 40 cM region of 7q. To further characterize this susceptibility locus, linkage analysis has now been completed on 170 multiplex IMGSAC families. Using a 5 cM marker grid, analysis of 125 sib pairs meeting stringent inclusion criteria resulted in a multipoint maximum LOD score (MLS) of 2.15 at D7S477, whereas analysis of all 153 sib pairs generated an MLS of 3.37. The 71 non-UK sib pairs now contribute to this linkage. Linkage disequilibrium mapping identified two regions of association-one lying under the peak of linkage, the other some 27 cM distal. These results are supported in part by findings in independent German and American singleton families.

Published
2016

8. The Disciplined Mind: Associations Between the Kentucky Inventory of Mindfulness Skills and Attention Control

Author

Sandra K. Loo, Susan L. Smalley, Brian M. Galla, T. Sigi Hale, and Anshu Shrestha

Subjects
Health (social science), Mindfulness, Social Psychology, Post hoc, Attentional control, Experimental and Cognitive Psychology, Developmental psychology, Test (assessment), Prolonged exposure, Developmental and Educational Psychology, medicine, Anxiety, medicine.symptom, Psychology, Self report, Applied Psychology, Stroop effect
Abstract

In an attempt to replicate and clarify previous research, we examined the associations between the Kentucky Inventory of Mindfulness Skills (KIMS) and measures of sustained (Continuous Performance Test; CPT) and executive (Stroop) attention in a community sample of adults (n = 106). After controlling for age, gender, education, socio-economic status, IQ, and depression and anxiety, analyses indicated that the KIMS-Observe scale predicted enhanced Stroop performance and reduced variability in attentional processing on the CPT. Post hoc analyses also provided evidence that the associative strength between KIMS-Observe and reduced CPT reaction time variability increased as a function of task block, suggestive of a protective effect against attentional lapses due to prolonged exposure to the CPT. While the present study failed to replicate previously reported associations between KIMS and attentional functioning, the consistency of current findings to conceptualizations of mindfulness suggests that KIMS-Observe taps important attentional processes thought to underlie mindfulness.

Published
2011

9. Familial Clustering and DRD4 Effects on Electroencephalogram Measures in Multiplex Families With Attention Deficit/Hyperactivity Disorder

Author

James J. McGough, James T. McCracken, Sandra K. Loo, T. Sigi Hale, Anshu Shrestha, Susan L. Smalley, Grant Hanada, James Macion, and Stanley F. Nelson

Subjects
Candidate gene, medicine.diagnostic_test, biology, Electroencephalography, medicine.disease, medicine.disease_cause, Developmental psychology, Psychiatry and Mental health, Endophenotype, mental disorders, Heredity, medicine, Dopamine receptor D4, biology.protein, Developmental and Educational Psychology, Attention deficit hyperactivity disorder, Beta Rhythm, Sibling, Psychology, Clinical psychology
Abstract

Objective The current study tests electroencephalogram (EEG) measures as a potential endophenotype for attention deficit/hyperactivity disorder (ADHD) by examining sibling and parent–offspring similarity, familial clustering with the disorder, and association with the dopamine receptor D4 (DRD4) candidate gene. Method The sample consists of 531 participants (191 parents and 340 children) from 132 multiplex families with ADHD who participated in a larger genetics study. All members of the families underwent extensive assessment including semi-structured diagnostic interviews and EEG recording. Results Strong sibling similarity and parent–offspring correlations in EEG power emerged, suggesting high trait heritability. Increased theta power was observed among children with ADHD when compared with unaffected children, and there were no differences according to ADHD subtype. Within the parent sample, ADHD diagnostic status and ADHD subtype group differences emerged in the theta, alpha, and beta frequency bands. DRD4 effects for both parents and children were apparent in the beta frequency band and for children only in the theta frequency band. Conclusions This study suggests that EEG measures are a promising avenue of study in the search for putative endophenotypes for ADHD, and that variability at the DRD4 gene may contribute to this endophenotype.

Published
2010

10. On Genome-wide Association Studies for Family-Based Designs: An Integrative Analysis Approach Combining Ascertained Family Samples with Unselected Controls

Author

Alexandre A. Todorov, Eric Mick, Sungho Won, Benjamin M. Neale, Joseph Biederman, Scott T. Weiss, Barbara Franke, Richard Anney, Jessica Lasky-Su, Christoph Lange, Susan L. Smalley, Stephen V. Faraone, and Sandra K. Loo

Subjects
Research design, Genotype, Computer science, Population, Genome-wide association study, Population stratification, Bioinformatics, Statistical power, Genomic disorders and inherited multi-system disorders [IGMD 3], 03 medical and health sciences, 0302 clinical medicine, Report, Statistics, Genetics, Humans, Computer Simulation, Genetics(clinical), p-value, education, Genetics (clinical), 030304 developmental biology, Genetic association, 0303 health sciences, education.field_of_study, Confounding, Models, Theoretical, Phenotype, Research Design, Case-Control Studies, Functional Neurogenomics [DCN 2], 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Contains fulltext : 87223.pdf (Publisher’s version ) (Closed access) Large numbers of control individuals with genome-wide genotype data are now available through various databases. These controls are regularly used in case-control genome-wide association studies (GWAS) to increase the statistical power. Controls are often "unselected" for the disease of interest and are not matched to cases in terms of confounding factors, making the studies more vulnerable to confounding as a result of population stratification. In this communication, we demonstrate that family-based designs can integrate unselected controls from other studies into the analysis without compromising the robustness of family-based designs against genetic confounding. The result is a hybrid case-control family-based analysis that achieves higher power levels than population-based studies with the same number of cases and controls. This strategy is widely applicable and works ideally for all situations in which both family and case-control data are available. The approach consists of three steps. First, we perform a standard family-based association test that does not utilize the between-family component. Second, we use the between-family information in conjunction with the genotypes from unselected controls in a Cochran-Armitage trend test. The p values from this step are then calculated by rank ordering the individual Cochran-Armitage trend test statistics for the genotype markers. Third, we generate a combined p value with the association p values from the first two steps. Simulation studies are used to assess the achievable power levels of this method compared to standard analysis approaches. We illustrate the approach by an application to a GWAS of attention deficit hyperactivity disorder parent-offspring trios and publicly available controls.

Published
2010
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11. Effects of Mindful Awareness Practices on Executive Functions in Elementary School Children

Author

Lisa Flook, Susan Kaiser-Greenland, M. Jennifer Kitil, Eric Ishijima, Brian M. Galla, Jill Locke, Susan L. Smalley, and Connie Kasari

Subjects
Multivariate analysis, Mindfulness, media_common.quotation_subject, education, Parent reports, Metacognition, Cognition, Self-control, Executive functions, Education, law.invention, Developmental psychology, Psychiatry and Mental health, Randomized controlled trial, law, Developmental and Educational Psychology, Psychology, Applied Psychology, Clinical psychology, media_common
Abstract

A school-based program of mindful awareness practices (MAPs) was evaluated in a randomized control study of 64 second- and third-grade children ages 7–9 years. The program was delivered for 30 minutes, twice per week, for 8 weeks. Teachers and parents completed questionnaires assessing children's executive function immediately before and following the 8-week period. Multivariate analysis of covariance on teacher and parent reports of executive function (EF) indicated an interaction effect between baseline EF score and group status on posttest EF. That is, children in the MAPs group who were less well regulated showed greater improvement in EF compared with controls. Specifically, those children starting out with poor EF who went through the MAPs training showed gains in behavioral regulation, metacognition, and overall global executive control. These results indicate a stronger effect of MAPs on children with executive function difficulties. The finding that both teachers and parents reported changes sugg...

Published
2010

12. Independent Contributions of Cognitive Functioning and Social Risk Factors to Symptoms of ADHD in Two Nordic Populations-Based Cohorts

Author

Gunilla Bohlin, Einar Heiervang, Anja Taanila, Irma Moilanen, Alina Rodriguez, Sandra K. Loo, Linda Forssman, Astri J. Lundervold, Susan L. Smalley, and Marjo-Riitta Järvelin

Subjects
Male, Norwegian, Neuropsychological Tests, Impulsivity, Severity of Illness Index, Developmental psychology, Developmental and Educational Psychology, medicine, Humans, Psychology, Attention deficit hyperactivity disorder, Risk factor, Child, Finland, Norway, Cognitive disorder, Cognition, medicine.disease, Social relation, language.human_language, Diagnostic and Statistical Manual of Mental Disorders, Neuropsychology and Physiological Psychology, Attention Deficit Disorder with Hyperactivity, Population Surveillance, Cohort, language, Female, medicine.symptom, Cognition Disorders, Clinical psychology
Abstract

This study examined independent contributions of executive functioning (EF), state regulation (SR), and social risk factors to symptom dimensions of attention deficit hyperactivity disorder (ADHD) in two cohorts, which included 221 Norwegian children and 294 Finnish adolescents. Independent contributions of EF and SR were shown in the Norwegian cohort and EF contributed independently in the Finnish cohort. When controlling for each symptom dimension, cognitive functioning and social risk factors were differentially associated with inattention and hyperactivity/impulsivity symptoms. The results show the need to include both social risk factors and cognitive functioning to obtain a better understanding of ADHD symptoms.

Published
2009

13. Mindfulness and attention deficit hyperactivity disorder

Author

T. Sigi Hale, James J. McGough, Anshu Shrestha, Lisa Flook, Sandra K. Loo, Steven P. Reise, and Susan L. Smalley

Subjects
Adult, Male, Self-transcendence, Mindfulness, media_common.quotation_subject, behavioral disciplines and activities, Article, Developmental psychology, Arts and Humanities (miscellaneous), Surveys and Questionnaires, Self-directedness, mental disorders, medicine, Humans, Attention deficit hyperactivity disorder, Personality, Big Five personality traits, media_common, Novelty seeking, Awareness, Middle Aged, medicine.disease, Clinical Psychology, Attention Deficit Disorder with Hyperactivity, Regression Analysis, Female, Temperament, Psychology
Abstract

Attention deficit hyperactivity disorder (ADHD) is a disorder characterized by attentional difficulties. Mindfulness is a receptive attention to present experience. Both ADHD and mindfulness are associated with attention and personality. This study tests whether individuals with ADHD have lower mindfulness scores than controls and, if true, whether personality contributes to these differences. One hundred and five adults (half with ADHD) were assessed for mindfulness, using the Kentucky Inventory of Mindfulness Skills, and personality, using the Tridimensional Character Inventory. Individuals with ADHD report themselves as less mindful than non-ADHD controls and more novelty-seeking, less self-directed, and more self-transcendent. Mindfulness is negatively associated with ADHD and positively associated with self-directedness and self-transcendence. Analyses of subscales of mindfulness suggest that ADHD is associated most with the "Acting in Awareness" dimension, perhaps because of shared items reflecting attentional variability. The current findings support that a large portion of variability in trait mindfulness can be explained by ADHD status and personality traits of self-directedness and self-transcendence. It further suggests that interventions that increase mindfulness might improve symptoms of ADHD and increase self-directedness and/or self-transcendence.

Published
2009

14. Cortical activity patterns in ADHD during arousal, activation and sustained attention

Author

James T. McCracken, Sandra K. Loo, T. Sigi Hale, Susan L. Smalley, James J. McGough, Grant Hanada, and James Macion

Subjects
Adult, Male, Cognitive Neuroscience, media_common.quotation_subject, Central nervous system, Experimental and Cognitive Psychology, Neuropsychological Tests, Electroencephalography, Brain mapping, Article, Arousal, Behavioral Neuroscience, Low arousal theory, medicine, Humans, Attention, Beta Rhythm, media_common, Cerebral Cortex, Analysis of Variance, Brain Mapping, medicine.diagnostic_test, Spectrum Analysis, Middle Aged, Alpha Rhythm, Electrophysiology, medicine.anatomical_structure, Attention Deficit Disorder with Hyperactivity, Female, Psychology, Neuroscience, Vigilance (psychology)
Abstract

The goal of the present study is to test whether there are Attention-Deficit Hyperactivity Disorder (ADHD)-related differences in brain electrical activity patterns across arousal, activation and vigilance states.The sample consists of 80 adults (38 with ADHD and 42 non-ADHD controls) who were recruited for a family study on the genetics of ADHD. Patterns of cortical activity were measured using electroencephalography (EEG) during baseline and sustained attention conditions and compared according to ADHD diagnostic status. Cortical activity was examined separately for the first, middle, and last 5-min of the sustained attention task to assess whether patterns differed over time and according to ADHD status.In frontal and parietal regions, patterns of activation in the alpha (8-10 Hz) range differed according to ADHD status, indicating increased cortical arousal among ADHD subjects. Beta power (13-14 and 17-18 Hz) also differed between ADHD and controls, indicating increased cortical activation is associated with ADHD. Behavioral performance on the sustained attention task did not differ significantly by diagnosis. EEG correlates of cognitive performance differed significantly ADHD diagnosis and were primarily in frontal regions. Brain activation patterns recorded during the sustained attention task suggest that the ADHD group exhibited significantly increased cortical activation at the end of the task when compared to controls.Adults with ADHD may have different neural organization primarily in frontal regions which results in the need for continually high levels of cortical activation to maintain sustained attention.

Published
2009

15. Genomewide association studies: history, rationale, and prospects for psychiatric disorders

Author

Stephan Ripke, Weihua Guan, Alan R. Sanders, Laura Nisenbaum, Barbara Franke, Patrick F. Sullivan, P. McGuffin, Pamela Sklar, Cathryn M. Lewis, Aravinda Chakravarti, Neale Bm, Nicholas G. Martin, Ann E. Pulver, Richard Anney, Guy A. Rouleau, Marcella Rietschel, Jordan W. Smoller, Claudine Laurent, Brien P. Riley, Thomas F. Wienker, Roy H. Perlis, Witte J.G. Hoogendijk, Ruchi Upmanyu, Jaana Suvisaari, Christina M. Hultman, Patrick J. McGrath, Susan L. Santangelo, Michael Conlon O'Donovan, Jennifer Stone, Dieter Wildenaver, Nicholas John Craddock, Edwin J. C. G. van den Oord, William Coryell, Gerard D. Schellenberg, Pablo V. Gejman, Arnoldo Frigessi, Anita Thapar, Michael Steffens, Bryan J. Mowry, Mark J. Daly, Susan L. Slager, Eve H. Pickering, Michael Gill, Audra Moran, Eco J. C. de Geus, Shaun Purcell, John P. Rice, Douglas F. Levinson, Patrick Sullivan, S. P. Hamilton, Peter Szatmari, William Lawson, Anil K. Malhotra, James B. Potash, William A. Scheftner, Federica Tozzi, Aiden Corvin, J. J. McGough, John I. Nurnberger, Alexandre A. Todorov, Joseph D. Buxbaum, Jonathan Sebat, Susan L. Smalley, Jung-Ying Tzeng, Lindsey Kent, Walter J. Muir, Michael Boehnke, Phillip Awadalla, Thomas Lehner, Valentina Moskvina, Peter Holmans, Hugh Gurling, Veronica J. Vieland, Stephen W. Scherer, Susanne Lucae, Ayman H. Fanous, Danyu Lin, Naomi R. Wray, Sibylle G. Schwab, Joseph Piven, Dorret I. Boomsma, Tiffany A. Greenwood, Sven Cichon, James S. Sutcliffe, Manuel A. R. Ferreira, Frank Dudbridge, A.H.M. Willemsen, Todd Lencz, Stafam Kloiber, Danielle Posthuma, James Offord, Matthew Flickinger, Michael John Owen, David St Clair, Roel A. Ophoff, Bernie Devlin, Douglas M. Ruderfer, Leena Peltonen, Brenda W.J.H. Penninx, Richard D. Todd, Kenneth S. Kendler, Sari Kivikko, Dan E. Arking, Elizabeth G. Holliday, Markus M. Noethen, René Breuer, John R. Kelsoe, Thomas G. Schulze, Josephine Elia, Edwin H. Cook, Nicholas J. Schork, Douglas Blackwood, Margit Burmeister, Myrna M. Weissman, Hakon Hakonarson, Laura J. Scott, Eric Mick, Pierandrea Muglia, Ole A. Andreassen, Jun Li, Stephen V. Faraone, Jan K. Buitelaar, Biological Psychology, Neuroscience Campus Amsterdam - Anxiety & Depression, and EMGO+ - Mental Health

Subjects
Netherlands Twin Register (NTR), medicine.medical_specialty, Linkage disequilibrium, Genetics and epigenetic pathways of disease [NCMLS 6], Genetic Linkage, Single-nucleotide polymorphism, Genome-wide association study, Biology, History, 21st Century, Polymorphism, Single Nucleotide, Article, Linkage Disequilibrium, Genomic disorders and inherited multi-system disorders [IGMD 3], 03 medical and health sciences, 0302 clinical medicine, medicine, Perception and Action [DCN 1], Humans, Copy-number variation, Bipolar disorder, Psychiatry, Alleles, 030304 developmental biology, Genetics, 0303 health sciences, Genome, Mental Disorders, History, 20th Century, medicine.disease, Genetic architecture, 3. Good health, Psychiatry and Mental health, Phenotype, Schizophrenia, Major depressive disorder, Functional Neurogenomics [DCN 2], 030217 neurology & neurosurgery
Abstract

Contains fulltext : 80575.pdf (Publisher’s version ) (Closed access) OBJECTIVE: The authors conducted a review of the history and empirical basis of genomewide association studies (GWAS), the rationale for GWAS of psychiatric disorders, results to date, limitations, and plans for GWAS meta-analyses. METHOD: A literature review was carried out, power and other issues discussed, and planned studies assessed. RESULTS: Most of the genomic DNA sequence differences between any two people are common (frequency >5%) single nucleotide polymorphisms (SNPs). Because of localized patterns of correlation (linkage disequilibrium), 500,000 to 1,000,000 of these SNPs can test the hypothesis that one or more common variants explain part of the genetic risk for a disease. GWAS technologies can also detect some of the copy number variants (deletions and duplications) in the genome. Systematic study of rare variants will require large-scale resequencing analyses. GWAS methods have detected a remarkable number of robust genetic associations for dozens of common diseases and traits, leading to new pathophysiological hypotheses, although only small proportions of genetic variance have been explained thus far and therapeutic applications will require substantial further effort. Study design issues, power, and limitations are discussed. For psychiatric disorders, there are initial significant findings for common SNPs and for rare copy number variants, and many other studies are in progress. CONCLUSIONS: GWAS of large samples have detected associations of common SNPs and of rare copy number variants with psychiatric disorders. More findings are likely, since larger GWAS samples detect larger numbers of common susceptibility variants, with smaller effects. The Psychiatric GWAS Consortium is conducting GWAS meta-analyses for schizophrenia, bipolar disorder, major depressive disorder, autism, and attention deficit hyperactivity disorder. Based on results for other diseases, larger samples will be required. The contribution of GWAS will depend on the true genetic architecture of each disorder.

Published
2009

16. Association of the cannabinoid receptor gene (CNR1) with ADHD and post-traumatic stress disorder

Author

Rita M. Cantor, May H. Yang, Sandra K. Loo, James T. McCracken, Leena Peltonen, Marjo-Ritta Jarvelin, Susan L. Smalley, Matthew N. Ogdie, Stanley F. Nelson, Ake T. Lu, James J. McGough, and Irma Moilanen

Subjects
Male, Parents, Oncology, Linkage disequilibrium, Comorbidity, Linkage Disequilibrium, Cohort Studies, Stress Disorders, Post-Traumatic, 0302 clinical medicine, Gene Frequency, Risk Factors, Medicine, Child, Receptors, Cannabinoid, Finland, Genetics (clinical), Genetics, 0303 health sciences, Traumatic stress, Middle Aged, Los Angeles, Psychiatry and Mental health, Female, Anxiety disorder, Adult, medicine.medical_specialty, Adolescent, Genotype, Polymorphism, Single Nucleotide, behavioral disciplines and activities, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Sex Factors, Internal medicine, mental disorders, Humans, SNP, Attention deficit hyperactivity disorder, Genetic Predisposition to Disease, Allele frequency, Alleles, Aged, 030304 developmental biology, business.industry, Siblings, Haplotype, Genetic Variation, medicine.disease, Logistic Models, Haplotypes, Attention Deficit Disorder with Hyperactivity, Case-Control Studies, business, 030217 neurology & neurosurgery
Abstract

Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder affecting some 5-10% of children and 4-5% of adults. The cannabinoid receptor gene (CNR1) is a positional candidate gene due to its location near an identified ADHD linkage peak on chromosome 6, its role in stress and dopamine regulation, its association with other psychiatric disorders that co-occur with ADHD, and its function in learning and memory. We tested SNP variants at the CNR1 gene in two independent samples-an unselected adolescent sample from Northern Finland, and a family-based sample of trios (an ADHD child and their parents). In addition to using the trios for association study, the parents (with and without ADHD) were used as an additional case/control sample of adults for association tests. ADHD and its co-morbid psychiatric disorders were examined. A significant association was detected for a SNP haplotype (C-G) with ADHD (P = 0.008). A sex by genotype interaction was observed as well with this haplotype posing a greater risk in males than females. An association of an alternative SNP haplotype in this gene was found for post-traumatic stress disorder (PTSD) (P = 0.04 for C-A, and P = 0.01 for C-G). These observations require replication, however, they suggest that the CNR1 gene may be a risk factor for ADHD and possibly PTSD, and that this gene warrants further investigation for a role in neuropsychiatric disorders.

Published
2008

17. CBCL Pediatric Bipolar Disorder Profile and ADHD: Comorbidity and Quantitative Trait Loci Analysis

Author

Stanley F. Nelson, James J. McGough, Sandra K. Loo, Shaunna L. Clark, Susan L. Smalley, Jeff Dang, and James T. McCracken

Subjects
Conduct Disorder, Male, medicine.medical_specialty, Bipolar Disorder, Generalized anxiety disorder, Adolescent, Genotype, Quantitative Trait Loci, Comorbidity, Personality Assessment, behavioral disciplines and activities, Article, Diagnosis, Differential, mental disorders, Developmental and Educational Psychology, medicine, Humans, Attention deficit hyperactivity disorder, Genetic Predisposition to Disease, Bipolar disorder, Child, Psychiatry, Child Behavior Checklist, Chromosome Mapping, Schedule for Affective Disorders and Schizophrenia, medicine.disease, Anxiety Disorders, Checklist, Psychiatry and Mental health, Cross-Sectional Studies, Phenotype, Attention Deficit Disorder with Hyperactivity, Attention Deficit and Disruptive Behavior Disorders, Conduct disorder, Child, Preschool, Chromosomes, Human, Pair 2, Anxiety, Female, medicine.symptom, Psychology, Genome-Wide Association Study, Clinical psychology
Abstract

Objective The pediatric bipolar disorder profilme of the Child Behavior Checklist (CBCL-PBD), a parent-completed measure that avoids clinician ideological bias, has proven useful in differentiating patients with attention-deficit/hyperactivity disorder (ADHD). We used CBCL-PBD profiles to distinguish patterns of comorbidity and to search for quantitative trait loci in a genomewide scan in a sample of multiple affected ADHD sibling pairs. Method A total of 540 ADHD subjects ages 5 to 18 years were assessed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version and CBCL. Parents were assessed with the Schedule for Affective Disorders and Schizophrenia-Lifetime version supplemented by the Schedule for Affective Disorders and Schizophrenia for School-Age Children for disruptive behavioral disorders. Patterns of psychiatric comorbidity were contrasted based on the CBCL-PBD profile. A quantitative trait loci variance component analysis was used to identify potential genomic regions that may harbor susceptibility genes for the CBCL-PBD quantitative phenotype. Results Bipolar spectrum disorders represented less than 2% of the overall sample. The CBCL-PBD classification was associated with increased generalized anxiety disorder ( p = .001), oppositional defiant disorder ( p = .008), conduct disorder ( p = .003), and parental substance abuse ( p = .005). A moderately significant linkage signal (multipoint maximum lod score=2.5) was found on chromosome 2q. Conclusions The CBCL-PBD profile distinguishes a subset of ADHD patients with significant comorbidity. Linkage analysis of the CBCL-PBD phenotype suggests certain genomic regions that merit further investigation for genes predisposing to severe psychopathology.

Published
2008

18. ADHD in the Northern Finnish Birth Cohort

Author

Susan L. Smalley and Sandra K. Loo

Subjects
medicine.medical_specialty, education.field_of_study, Population, Cognition, Retrospective cohort study, medicine.disease, behavioral disciplines and activities, British birth cohort studies, mental disorders, Cohort, Child and adolescent psychiatry, medicine, General Earth and Planetary Sciences, Attention deficit hyperactivity disorder, Psychology, education, Prospective cohort study, Psychiatry, General Environmental Science
Abstract

The Northern Finnish Birth Cohort (NFBC) study of Attention Deficit Hyperactivity Disorder (ADHD) was initiated in 2001 to identify risk genes and gene–by–environmental interactions underlying ADHD in a population-based cohort of adolescents who have been followed prospectively since their birth in 1986. The cohort is drawn from northern Finland (pop. 630,000), where the population consists primarily of two groups—an early settlement and a late settlement. The late settlement descended from a small number of families (or founders) who migrated there in the 17th century and expanded locally. The small number of founders in a region that is fairly geographically isolated has resulted in a “population isolate” that is invaluable to genetic studies of single gene (i.e., monogenic) disorders as well as disorders which are thought to be due to several genes (i.e., polygenic). The first set of five papers on the NFBC study of ADHD was recently published in the December 2007 issue of the Journal of the American Academy of Child and Adolescent Psychiatry, and this article will summarize those detailed papers to present the main conclusions drawn about ADHD, based on one of the largest population-based studies of ADHD. Readers are directed to that journal for the methods, detailed results, and a more extensive discussion of the conclusions. The NFBC provides a unique opportunity to examine the developmental trajectory of ADHD in a social setting where medication is not the primary approach to treating ADHD. In fact, very few of the almost 457 (ADHD = 188, Controls = 269) adolescents assessed during the study had ever received any pharmacological treatment. Despite striking differences in treatment approaches between northern Finland and the United States, the clinical characteristics, psychiatric comorbidity, and cognitive deficits associated with ADHD are very much alike. Thus, one of the first major conclusions from this set of studies is that, despite the controversy regarding the validity of the ADHD diagnosis, ADHD is a clearly recognizable condition with a relatively stable prevalence worldwide. Using DSM–IV diagnostic criteria in a population-based cohort of adolescents (ages 16–18) in northern Finland, the prevalence is 8.5%. The clinical characteristics of ADHD in this population are strikingly similar to other ADHD samples drawn around the world with more boys than girls being affected, similar rates of psychiatric comorbidity, and similar rates of persistence of ADHD from childhood into adolescence (~2/3). Description of the ascertainment method and clinical characteristics of the sample were described in the paper by Smalley and colleagues (Smalley et al., 2007). One goal of the study was to examine ADHD symptoms within a large popu

Published
2008

19. Association Analysis of Candidate Genes for ADHD on Chromosomes 5p13, 6q12, 16p and 17p

Author

Jeff Dang, James J. McGough, Matthew N. Ogdie, Stanley F. Nelson, Jenny M. Ekholm, James T. McCracken, and Susan L. Smalley

Subjects
Linkage (software), Genetics, Candidate gene, mental disorders, Positional candidate, Etiology, Susceptibility gene, Allele, Psychology, Gene, Developmental psychology, Genetic association
Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a common, heterogeneous psychiatric disorder of childhood displaying inattentive, hyperactive, and impulsive symptoms. Although the biological basis of ADHD remains unknown, it has been shown that genetic factors substantially contribute to the aetiology of the disorder. Our group has previously reported significant linkage to four chromosomal regions on 5p13, 6q12, 16p13 and 17p11 in genome-wide scans and subsequent fine-mapping. We selected nine positional candidate genes within the linkage intervals for study based on bio- logical plausibility. We analyzed at least 189 ADHD trios to determine if common variants in these genes have a major af- fect on ADHD risk. None yielded significant association. This does however not completely exclude these genes as poten- tial susceptibility genes for ADHD since it is plausible for common causal variants with low effect size to go undetected due to insufficient power of the study sample. We conclude that none of the tested alleles confer a major risk for develop- ing ADHD and that investigation of other genes within the linked regions is warranted.

Published
2007

20. Executive Functioning Among Finnish Adolescents With Attention-Deficit/Hyperactivity Disorder

Author

James T. McCracken, Lorie A. Humphrey, Sandra K. Loo, Marjo-Riitta Järvelin, Terttu Tapio, Hanna Ebeling, Irma Moilanen, Jeff Dang, Anja Taanila, James J. McGough, Susan L. Smalley, and May H. Yang

Subjects
Male, medicine.medical_specialty, Elementary cognitive task, Adolescent, Neuropsychological Tests, Severity of Illness Index, behavioral disciplines and activities, Cohort Studies, Catchment Area, Health, mental disorders, Reaction Time, Developmental and Educational Psychology, medicine, Humans, Attention deficit hyperactivity disorder, Cognitive skill, Effects of sleep deprivation on cognitive performance, Psychiatry, Finland, Working memory, Neuropsychology, Cognition, medicine.disease, Psychiatry and Mental health, Attention Deficit Disorder with Hyperactivity, Female, Cognition Disorders, Psychology, Cohort study
Abstract

Objective The present study examined cognitive functioning in a population sample of adolescents with and without attention-deficit/hyperactivity disorder (ADHD) from the Northern Finland Birth Cohort 1986. Method The sample consisted of 457 adolescents ages 16 to 18 who were assessed using a battery of cognitive tasks. Performance according to diagnostic group (control, behavior disorder, and ADHD) and sex was compared. Then, the effect of executive function deficit (EFD) was assessed by diagnostic group status on behavioral and cognitive measures. Results When compared to non-ADHD groups, adolescents with ADHD exhibited deficits on almost all of the cognitive measures. The behavior disorder group obtained scores that were generally intermediate between the ADHD and control groups, but exhibited deficits in intelligence and executive function similar to the ADHD group. Approximately half the ADHD sample had EFD; however, the type and presence of EFDs were not differentially related to cognitive performance as a function of diagnosis. Conclusions These findings indicate that EFDs are more frequent in ADHD than control or behavior disorder groups. EFDs are a general risk factor for poor cognitive functioning across multiple domains, irrespective of diagnostic status.

Published
2007

21. ADHD Symptoms and Subtypes: Relationship Between Childhood and Adolescent Symptoms

Author

Jouko Miettunen, Susan L. Smalley, Irma Moilanen, Sandra K. Loo, Anja Taanila, Tuula Hurtig, James J. McGough, Hanna Ebeling, and Marjo-Riitta Järvelin

Subjects
Male, medicine.medical_specialty, Adolescent, Severity of Illness Index, behavioral disciplines and activities, mental disorders, Severity of illness, Epidemiology, Developmental and Educational Psychology, medicine, Humans, Attention deficit hyperactivity disorder, Family, Prospective Studies, Parent-Child Relations, Family history, Child, Psychiatry, Prospective cohort study, Depression (differential diagnoses), Parenting, Recall, Age Factors, medicine.disease, Diagnostic and Statistical Manual of Mental Disorders, Psychiatry and Mental health, El Niño, Attention Deficit Disorder with Hyperactivity, Female, Factor Analysis, Statistical, Psychology
Abstract

Objective To study attention-deficit/hyperactivity disorder (ADHD) symptoms and DSM-IV subtypes in childhood and adolescence. Method A total of 457 adolescents ages 16 to 18 years from the Northern Finland Birth Cohort 1986 participated in an epidemiological survey for ADHD. After assessment with a diagnostic interview those with current or childhood ADHD were classified using DSM-IV criteria. Childhood diagnosis of ADHD was set according to retrospective recall. The characteristics and relationships in ADHD symptomatology in childhood and adolescence were studied in relation to behavioral problems and parental history of attentional problems. Results ADHD was reported more commonly in childhood than in adolescence and variations in subtype classification occurred. Those with childhood and adolescent diagnosis had endorsed specific inattentive symptoms more commonly, had greater comorbid major depression and/or oppositional defiant disorder, and had fathers with more reported attentional problems than those with only childhood diagnosis. In childhood, ADHD subtypes differed along symptom severity, but by adolescence these differences were no longer significant. Conclusions The persistence of ADHD from childhood to adolescence may be common. Specific inattentive symptoms, certain psychiatric comorbidity, and family history of attention problems (fathers specifically) contribute to the risk of persistent ADHD. ADHD subtype differences reflect symptom severity differences in childhood that are negligible by adolescence.

Published
2007

22. ADHD Candidate Gene Study in a Population-Based Birth Cohort: Association with DBH and DRD2

Author

Anu Loukola, Leena Peltonen, James J. McGough, Matthew N. Ogdie, Anja Taanila, Stanley F. Nelson, Sandra K. Loo, Teppo Varilo, Marjo-Riitta Järvelin, Irma Moilanen, Emma S. Nyman, Susan L. Smalley, and Tuula Hurtig

Subjects
Genetic Markers, Male, Candidate gene, Adolescent, Genotype, Dopamine beta-Hydroxylase, Genetic determinism, Cohort Studies, Dopamine, Dopamine receptor D2, Developmental and Educational Psychology, medicine, Humans, Attention deficit hyperactivity disorder, Allele, Alleles, DNA Primers, Genetics, Polymorphism, Genetic, Genetic heterogeneity, Receptors, Dopamine D3, medicine.disease, Diagnostic and Statistical Manual of Mental Disorders, Psychiatry and Mental health, Attention Deficit Disorder with Hyperactivity, Population Surveillance, Female, Psychology, Founder effect, medicine.drug
Abstract

Objective Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-onset disorder with a significant impact on public health. Although a genetic contribution to risk is evident, predisposing genetic determinants remain largely unknown despite extensive research. So far, the most promising candidate genes have been those involved in dopamine and serotonin pathways. This study tests a series of allelic variants within such candidate genes to determine their potential influence on ADHD susceptibility. Method We used a population sample ascertained from a birth cohort of a subpopulation of Finland, characterized by founder effect and isolation, thus minimizing genetic heterogeneity. The subjects were systematically ascertained using DSM-IV diagnostic criteria for ADHD from the Northern Finland Birth Cohort 1986 of more than 9,000 individuals, resulting in the study sample of 188 ADHD cases and 166 controls. We genotyped markers in 13 candidate genes, including critical components of dopamine and serotonin pathways. Results We report evidence for association of ADHD with allelic variants of the dopamine β-hydroxylase (DBH) and dopamine receptor D2 (DRD2) genes. Conclusions Our study supports the involvement of the dopamine pathway in the etiology of ADHD; specifically the genes DBH and DRD2 deserve more attention in further studies.

Published
2007

23. ADHD and comorbid disorders in relation to family environment and symptom severity

Author

Tuula Hurtig, Anja Taanila, Susan L. Smalley, Marjo-Riitta Järvelin, Irma Moilanen, James J. McGough, Hanna Ebeling, Jouko Miettunen, and Sandra K. Loo

Subjects
Male, medicine.medical_specialty, Adolescent, Comorbidity, macromolecular substances, Social Environment, Severity of Illness Index, complex mixtures, behavioral disciplines and activities, Surveys and Questionnaires, mental disorders, Severity of illness, Developmental and Educational Psychology, medicine, Child and adolescent psychiatry, Humans, Family, Psychiatry, Extramural, Mental Disorders, Symptom severity, Social environment, General Medicine, medicine.disease, Diagnostic and Statistical Manual of Mental Disorders, Psychiatry and Mental health, Attention Deficit Disorder with Hyperactivity, Pediatrics, Perinatology and Child Health, bacteria, Female, Psychology
Abstract

To examine the comorbidity of ADHD in association with family environment and the severity of ADHD.A screening for ADHD symptoms was conducted among adolescents in the Northern Finland 1986 Birth Cohort (N = 6622). A sample of those adolescents (n = 457), aged 16-18 years, with and without ADHD symptoms was assessed with a diagnostic interview (Kiddie-SADS-PL) and ADHD and comorbid disorders were studied in association with the family characteristics and the number of ADHD symptoms.Adolescents with ADHD had more commonly conduct disorder (P0.001), oppositional defiant disorder (P0.001), substance abuse (P0.001) and mild depression (P0.001) than adolescents without ADHD. Adolescents with ADHD and comorbid disorders had more ADHD symptoms (P0.001) than those with ADHD alone. Compared to adolescents with ADHD alone those with ADHD and comorbidity lived significantly more commonly in non-intact families, in low-income families, with mothers who were dissatisfied with life and with parents who showed little interest in their adolescents' activities.Adolescents who develop externalizing disorders comorbid to ADHD seem to suffer from a severe form of ADHD and live in family environments that may not provide sufficient support for optimal development of an adolescent with ADHD.

Published
2007

24. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

Author

Anita Thapar, Lena Backlund, Lindsey Kent, Walter J. Muir, A. Jeremy Willsey, Sandra K. Loo, Michael Boehnke, Christa Lese Martin, Ania Korszun, Guiomar Oliveira, Veronica J. Vieland, Stephen W. Scherer, René S. Kahn, Darina Czamara, Jeremy R. Parr, Michael E. Goddard, Willem A. Nolen, Josep Antoni Ramos-Quiroga, Stephen Sanders, Karola Rehnstroem, Nelson B. Freimer, Erin N. Smith, Ann Olincy, Ingrid Melle, Myrna M. Weissman, James A. Knowles, William Byerley, Aravinda Chakravarti, Shaun Purcell, Jens Treutlein, Sebastian Zoellner, Hakon Hakonarson, Susanne Lucae, Markus M. Noethen, Ian B. Hickie, Marion Friedl, Srinivasa Thirumalai, Stephen Newhouse, Joseph Piven, Andrew M. McIntosh, Cathryn M. Lewis, Srdjan Djurovic, Francis J. McMahon, Ayman H. Fanous, Bernie Devlin, Steven A. McCarroll, Alan F. Schatzberg, Peter Szatmari, Marta Ribasés, C. Robert Cloninger, Brenda W.J.H. Penninx, Gerard van Grootheest, Phil Lee, Richard Anney, Elaine K. Green, Geraldine Dawson, Joseph A. Sergeant, Digby Quested, Magdalena Gross, Jack D. Barchas, Nicholas G. Martin, Timothy W. Yu, Jouke-Jan Hottenga, Mark Lathrop, Federica Tozzi, Martin Hautzinger, Alysa E. Doyle, Cinnamon S. Bloss, Sandra Meier, Louise Gailagher, David A. Collier, Farooq Amin, Michael C. Neale, Martin Schalling, Lieuwe de Haan, Bru Cormand, Falk W. Lohoff, Jennifer Crosbie, Howard J. Edenberg, Aarno Palotie, Johannes H. Smit, Robert Freedman, Katherine Gordon-Smith, Michele L. Pergadia, Enda M. Byrne, Hans-Christoph Steinhausen, Benjamin M. Neale, Anjali K. Henders, Michele T. Pato, Manuel Mattheisen, Urban Ösby, Edward M. Scolnick, Evaristus A. Nwulia, Fritz Poustka, Gonneke Willemsen, Andrew C. Heath, David St. Cair, Emma M. Quinn, I. Nicol Ferrier, John R. Kelsoe, Vanessa Hus, Andrew McQuillin, John P. Rice, William M. McMahon, Joseph Biederman, Danyu Lin, Wolfgang Maier, Frans G. Zitman, Josephine Elia, Nicholas J. Schork, Stéphane Jamain, Lizzy Rossin, Jubao Duan, Ingrid Agartz, Devin Absher, Jordan W. Smoller, Matthew W. State, Richard M. Myers, Shrikant Mane, Carlos N. Pato, William E. Bunney, Marian L. Hamshere, Manfred Uhr, Nicholas John Craddock, Astrid M. Vicente, Tobias Banaschewski, David Curtis, Anne Farmer, Scott D. Gordon, Anna K. Kaehler, Eric M. Morrow, Marcella Rietschel, Patrik K. E. Magnusson, Klaus-Peter Lesch, Rebecca McKinney, Jana Strohmaier, Thomas F. Wienker, Pablo V. Gejman, Douglas Blackwood, Maria Helena Pinto de Azevedo, Tiffany A. Greenwood, Don H. Linszen, Daniel L. Koller, Richard Bruggeman, Vinay Puri, Naomi R. Wray, Stanley J. Watson, Elena Maestrini, Valentina Moskvina, Frank Dudbridge, Danielle Posthuma, Edward G. Jones, Lambertus Klei, Sarah E. Bergen, Fan Meng, Steven P. Hamilton, Guy A. Rouleau, Pierandrea Muglia, Mikael Landén, Stephanie H. Witt, Laramie E. Duncan, Stanley Zammit, Judith A. Badner, Florian Holsboer, Eco J. C. de Geus, Daniel Moreno-De-Luca, Benjamin S. Pickard, Gunnar Morken, Michael Conlon O'Donovan, Michael Steffens, Kathryn Roeder, Dorret I. Boomsma, Paul D. Shilling, Stephan Ripke, Nigel Williams, Jeremy M. Silverman, David Craig, Mark J. Daly, Michael Bauer, Detelina Grozeva, Markus J. Schwarz, Peter Holmans, Hugh Gurling, T. Scott Stroup, Aribert Rothenberger, Gary Donohoe, Eric Fombonne, Joseph D. Buxbaum, Matthew Flicldnger, Bryan J. Mowry, Thomas Hansen, Ina Giegling, Grant W. Montgomery, Caroline M. Nievergelt, Susan L. Smalley, Jung-Ying Tzeng, David H. Ledbetter, Christopher A. Walsh, Gerard D. Schellenberg, Sarah E. Medland, Robert D. Oades, James B. Potash, Dan E. Arking, Johannes Schumacher, Michael Gill, James J. McGough, Jennifer L. Moran, Donald W. Black, Sian Caesar, Neelroop N. Parikshak, Ian W. Craig, Sabine M. Klauck, Wade H. Berrettini, T. Foroud, Peter P. Zandi, Inez Myin-Germeys, Marcus Ising, Sven Cichon, Alexandre A. Todorov, Mònica Bayés, Thomas Werge, Susan L. Slager, Stanley I. Shyn, Jim van Os, Derek W. Morris, Douglas M. Ruderfer, Thomas W. Muehleisen, Matthew C. Keller, Susmita Datta, Ian Jones, John B. Vincent, James L. Kennedy, Anthony P. Monaco, Jianxin Shi, Dale R. Nyholt, Bruno Etain, Christine Fraser, Paul Cormican, Miguel Casas, Radhika Kandaswamy, Gerome Breen, Stephen V. Faraone, Jonna Kuntsi, Thomas Bettecken, Witte J.G. Hoogendijk, Nancy G. Buccola, Franziska Degenhardt, Lyudmila Georgieva, Marion Leboyer, Alan R. Sanders, John Strauss, Dan Rujescu, Russell Schachar, Helena Medeiros, Lisa Jones, Peter M. Visscher, Lauren A. Weiss, René Breuer, John I. Nurnberger, Andreas Reif, Phoenix Kwan, Vihra Milanova, Chunyu Liu, Martin A. Kohli, Donald J. MacIntyre, Nicholas Bass, Khalid Choudhury, Edwin H. Cook, Catherine Lord, Andrew D. Paterson, Jobst Meyer, Richard P. Ebstein, Zhaoming Zhao, Niklas Laengstroem, Thomas G. Schulze, Peter Propping, Wei Xu, Robert C. Thompson, Kimberly Chambert, Jonathan Pimm, Ivan Nikolov, Pamela A. F. Madden, Kevin A. McGhee, Jacob Lawrence, Jan K. Buitelaar, Andres Ingason, Christine M. Freitag, Robert Krasucki, Wiepke Cahn, Rita M. Cantor, Christina M. Hultman, Melvin G. McInnis, Catalina Betancur, Eftichia Duketis, Michael T. Murtha, Thomas H. Wassink, Philip Asherson, John S. Witte, Elaine Kenny, Edmund J.S. Sonuga-Barke, Lydia Krabbendam, Line Olsen, Agatino Battaglia, Laura J. Scott, Annette M. Hartmann, Yunjung Kim, Richard O. Day, Edwin J. C. G. van den Oord, Ole A. Andreassen, Herbert Roeyers, Michael John Owen, Colm O'Dushlaine, Peng Zhang, Morten Mattingsdal, Michael L. Cuccaro, Margaret A. Pericak-Vance, Joachim Hallmayer, Jun Li, Pamela B. Mahon, Elisabeth B. Binder, William A. Scheftner, Daniel H. Geschwind, Christel M. Middeldorp, Josef Frank, Keith Matthews, Jennifer K. Lowe, Paul Lichtenstein, Verneri Anttila, Pamela Sklar, Szabocls Szelinger, Roel A. Ophoff, Peter McGuffin, Stefan Herms, Bettina Konte, George Kirov, Hilary Coon, Maria Hipolito, Louise Frisén, Kenneth S. Kendler, Frank Bellivier, James S. Sutdiffe, Jeffrey A. Lieberman, Todd Lencz, Susanne Hoefels, Alan W. McLean, Barbara Franke, Huda Akil, Soumya Raychaudhuri, Ellen M. Wijsman, Vishwajit L. Nimgaonkar, Roy H. Perlis, Patrick J. McGrath, Susan L. Santangelo, William Coryell, Henrik B. Rasmussen, Weihua Guan, William Lawson, Elliot S. Gershon, Sean Ennis, Aiden Corvin, Allan H. Young, Thomas B. Barrett, Jonathan L. Haines, Douglas F. Levinson, Ana Miranda, Anil K. Malhotra, S. Hong Lee, Stan F. Nelson, Anthony J. Bailey, Patrick F. Sullivan, Dorothy E. Grice, Lefkos T. Middleton, Bertram Mueller-Myhsok, Michael R. Barnes, Adebayo Anjorin, O'Dushlaine, C, Rossin, L, Lee, Ph, Duncan, L, Parikshak, Nn, Newhouse, S, Ripke, S, Neale, Bm, Purcell, Sm, Posthuma, D, Nurnberger, Ji, Lee, Sh, Faraone, Sv, Perlis, Rh, Mowry, Bj, Thapar, A, Goddard, Me, Witte, J, Absher, D, Agartz, I, Akil, H, Amin, F, Andreassen, Oa, Anjorin, A, Anney, R, Anttila, V, Arking, De, Asherson, P, Azevedo, Mh, Backlund, L, Badner, Ja, Bailey, Aj, Banaschewski, T, Barchas, Jd, Barnes, Mr, Barrett, Tb, Bass, N, Battaglia, A, Bauer, M, Bayés, M, Bellivier, F, Bergen, Se, Berrettini, W, Betancur, C, Bettecken, T, Biederman, J, Binder, Eb, Black, Dw, Blackwood, Dh, Bloss, C, Boehnke, M, Boomsma, Di, Breuer, R, Bruggeman, R, Cormican, P, Buccola, Ng, Buitelaar, Jk, Bunney, We, Buxbaum, Jd, Byerley, Wf, Byrne, Em, Caesar, S, Cahn, W, Cantor, Rm, Casas, M, Chakravarti, A, Chambert, K, Choudhury, K, Cichon, S, Mattheisen, M, Cloninger, Cr, Collier, Da, Cook, Eh, Coon, H, Cormand, B, Corvin, A, Coryell, Wh, Craig, Dw, Craig, Iw, Crosbie, J, Cuccaro, Ml, Curtis, D, Czamara, D, Datta, S, Dawson, G, Day, R, De Geus, Ej, Degenhardt, F, Djurovic, S, Donohoe, Gj, Doyle, Ae, Duan, J, Dudbridge, F, Duketis, E, Ebstein, Rp, Edenberg, Hj, Elia, J, Ennis, S, Etain, B, Fanous, A, Farmer, Ae, Ferrier, In, Flickinger, M, Fombonne, E, Foroud, T, Frank, J, Franke, B, Fraser, C, Freedman, R, Freimer, Nb, Freitag, Cm, Friedl, M, Frisén, L, Gallagher, L, Gejman, Pv, Georgieva, L, Gershon, E, Giegling, I, Gill, M, Gordon, Sd, Gordon-Smith, K, Green, Ek, Greenwood, Ta, Grice, De, Gross, M, Grozeva, D, Guan, W, Gurling, H, De Haan, L, Haines, Jl, Hakonarson, H, Hallmayer, J, Hamilton, Sp, Hamshere, Ml, Hansen, Tf, Hartmann, Am, Hautzinger, M, Heath, Ac, Henders, Ak, Herms, S, Hickie, Ib, Hipolito, M, Hoefels, S, Holsboer, F, Hoogendijk, Wj, Hottenga, Jj, Hultman, Cm, Hus, V, Ingason, A, Ising, M, Jamain, S, Jones, Eg, Jones, I, Jones, L, Tzeng, Jy, Kähler, Ak, Kahn, R, Kandaswamy, R, Keller, Mc, Kennedy, Jl, Kenny, E, Kent, L, Kim, Y, Kirov, Gk, Klauck, Sm, Klei, L, Knowles, Ja, Kohli, Ma, Koller, Dl, Konte, B, Korszun, A, Krabbendam, L, Krasucki, R, Kuntsi, J, Kwan, P, Landén, M, Längström, N, Lathrop, M, Lawrence, J, Lawson, Wb, Leboyer, M, Ledbetter, Dh, Lencz, T, Lesch, Kp, Levinson, Df, Lewis, Cm, Li, J, Lichtenstein, P, Lieberman, Ja, Lin, Dy, Linszen, Dh, Liu, C, Lohoff, Fw, Loo, Sk, Lord, C, Lowe, Jk, Lucae, S, Macintyre, Dj, Madden, Pa, Maestrini, E, Magnusson, Pk, Mahon, Pb, Maier, W, Malhotra, Ak, Mane, Sm, Martin, Cl, Martin, Ng, Matthews, K, Mattingsdal, M, Mccarroll, Sa, Mcghee, Ka, Mcgough, Jj, Mcgrath, Pj, Mcguffin, P, Mcinnis, Mg, Mcintosh, A, Mckinney, R, Mclean, Aw, Mcmahon, Fj, Mcmahon, Wm, Mcquillin, A, Medeiros, H, Medland, Se, Meier, S, Melle, I, Meyer, J, Middeldorp, Cm, Middleton, L, Milanova, V, Miranda, A, Monaco, A, Montgomery, Gw, Moran, Jl, Moreno-De-Luca, D, Morken, G, Morris, Dw, Morrow, Em, Moskvina, V, Muglia, P, Mühleisen, Tw, Muir, Wj, Müller-Myhsok, B, Murtha, M, Myers, Rm, Myin-Germeys, I, Neale, Mc, Nelson, Sf, Nievergelt, Cm, Nikolov, I, Nimgaonkar, V, Nolen, Wa, Nöthen, Mm, Nwulia, Ea, Nyholt, Dr, Oades, Rd, Olincy, A, Oliveira, G, Olsen, L, Ophoff, Ra, Osby, U, Owen, Mj, Palotie, A, Parr, Jr, Paterson, Ad, Pato, Cn, Pato, Mt, Penninx, Bw, Pergadia, Ml, Pericak-Vance, Ma, Pickard, B, Pimm, J, Piven, J, Potash, Jb, Poustka, F, Propping, P, Puri, V, Quested, Dj, Quinn, Em, Ramos-Quiroga, Ja, Rasmussen, Hb, Raychaudhuri, S, Rehnström, K, Reif, A, Ribasés, M, Rice, Jp, Rietschel, M, Roeder, K, Roeyers, H, Rothenberger, A, Rouleau, G, Ruderfer, D, Rujescu, D, Sanders, Ar, Sanders, Sj, Santangelo, Sl, Sergeant, Ja, Schachar, R, Schalling, M, Schatzberg, Af, Scheftner, Wa, Schellenberg, Gd, Scherer, Sw, Schork, Nj, Schulze, Tg, Schumacher, J, Schwarz, M, Scolnick, E, Scott, Lj, Shi, J, Shilling, Pd, Shyn, Si, Silverman, Jm, Slager, Sl, Smalley, Sl, Smit, Jh, Smith, En, Sonuga-Barke, Ej, St Clair, D, State, M, Steffens, M, Steinhausen, Hc, Strauss, J, Strohmaier, J, Stroup, T, Sutcliffe, J, Szatmari, P, Szelinger, S, Thirumalai, S, Thompson, Rc, Todorov, Aa, Tozzi, F, Treutlein, J, Uhr, M, van den Oord, Jc, Van Grootheest, G, Van Os, J, Vicente, A, Vieland, Vj, Vincent, Jb, Visscher, Pm, Walsh, Ca, Wassink, Th, Watson, Sj, Weissman, Mm, Werge, T, Wienker, Tf, Wijsman, Em, Willemsen, G, Williams, N, Willsey, Aj, Witt, Sh, Xu, W, Young, Ah, Yu, Tw, Zammit, S, Zandi, Pp, Zhang, P, Zitman, Fg, Zöllner, S, Devlin, B, Kelsoe, Jr, Sklar, P, Daly, Mj, O'Donovan, Mc, Craddock, N, Kendler, K, Weiss, La, Wray, Nr, Zhao, Z, Geschwind, Dh, Sullivan, Pf, Smoller, Jw, Holmans, Pa, Breen, G., Génétique de l'autisme = Genetics of Autism (NPS-01), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Human genetics, Psychiatry, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, Child and Adolescent Psychiatry / Psychology, Epidemiology, Gastroenterology & Hepatology, Hematology, University of St Andrews. School of Medicine, University of St Andrews. Institute of Behavioural and Neural Sciences, Psychiatrie & Neuropsychologie, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), RS: MHeNs - R2 - Mental Health, ANS - Amsterdam Neuroscience, Adult Psychiatry, Child Psychiatry, Universitat de Barcelona, Perceptual and Cognitive Neuroscience (PCN), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Complex Trait Genetics, Biological Psychology, Educational Neuroscience, Clinical Neuropsychology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, LEARN! - Social cognition and learning, LEARN! - Brain, learning and development, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), O'Dushlaine, Colm, Rossin, Lizzy, Lee, Phil H, Duncan, Laramie, Lee, S Hong, Breen, Gerome, International Inflammatory Bowel Disease Genetics Consortium (IIBDGC), Network and Pathway Analysis Subgroup of the Psychiatric Genomics Consortium, and Myin-Germeys, Inez

Subjects
Netherlands Twin Register (NTR), Statistical methods, Autism, Medizin, LOCI, Genome-wide association study, heritability, Genome-wide association studies, Histones, Genètica mèdica, 0302 clinical medicine, Histone methylation, Databases, Genetic, 2.1 Biological and endogenous factors, Psychology, GWAS, Aetiology, Psychiatric genetics, R2C, bipolar disorder, Psychiatry, 0303 health sciences, Disorders, Loci, Depression, General Neuroscience, Mental Disorders, Medical genetics, METHYLATION, Brain, 3rd-DAS, Serious Mental Illness, Psychiatric Disorders, 3. Good health, Histone, Mental Health, Schizophrenia, Mental Disorder, Cognitive Sciences, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Promoters, BDC, BURDEN, RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry, Human, Signal Transduction, medicine.medical_specialty, DISORDERS, Genomics, Network and Pathway Analysis Subgroup of Psychiatric Genomics Consortium, Burden, Biology, Methylation, Article, Biological pathway, PROMOTERS, 03 medical and health sciences, Databases, Genetic, medicine, Genetics, Humans, Genetic Predisposition to Disease, histone methylation, Bipolar disorder, Psiquiatria, AUTISM, 030304 developmental biology, Genetic association, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Neurology & Neurosurgery, Neuroscience (all), Human Genome, Neurosciences, medicine.disease, Brain Disorders, Good Health and Well Being, DE-NOVO MUTATIONS, Perturbações do Desenvolvimento Infantil e Saúde Mental, RC0321, Genome-wide Association Studies, De-novo mutations, major depression, Neuroscience, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

G.B. and S.N. acknowledge funding support for this work from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. P.H.L. is supported by US National Institute of Mental Health (NIMH) grant K99MH101367. Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders. Postprint

Published
2015

25. Joint Analysis of Psychiatric Disorders Increases Accuracy of Risk Prediction for Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

Author

Robert Maier, Gerhard Moser, Guo-Bo Chen, Stephan Ripke, William Coryell, James B. Potash, William A. Scheftner, Jianxin Shi, Myrna M. Weissman, Christina M. Hultman, Mikael Landén, Douglas F. Levinson, Kenneth S. Kendler, Jordan W. Smoller, Naomi R. Wray, S. Hong Lee, Devin Absher, Ingrid Agartz, Huda Akil, Farooq Amin, Ole A. Andreassen, Adebayo Anjorin, Richard Anney, Dan E. Arking, Philip Asherson, Maria H. Azevedo, Lena Backlund, Judith A. Badner, Anthony J. Bailey, Tobias Banaschewski, Jack D. Barchas, Michael R. Barnes, Thomas B. Barrett, Nicholas Bass, Agatino Battaglia, Michael Bauer, Mònica Bayés, Frank Bellivier, Sarah E. Bergen, Wade Berrettini, Catalina Betancur, Thomas Bettecken, Joseph Biederman, Elisabeth B. Binder, Donald W. Black, Douglas H.R. Blackwood, Cinnamon S. Bloss, Michael Boehnke, Dorret I. Boomsma, Gerome Breen, René Breuer, Richard Bruggeman, Nancy G. Buccola, Jan K. Buitelaar, William E. Bunney, Joseph D. Buxbaum, William F. Byerley, Sian Caesar, Wiepke Cahn, Rita M. Cantor, Miguel Casas, Aravinda Chakravarti, Kimberly Chambert, Khalid Choudhury, Sven Cichon, C. Robert Cloninger, David A. Collier, Edwin H. Cook, Hilary Coon, Bru Cormand, Paul Cormican, Aiden Corvin, William H. Coryell, Nicholas Craddock, David W. Craig, Ian W. Craig, Jennifer Crosbie, Michael L. Cuccaro, David Curtis, Darina Czamara, Mark J. Daly, Susmita Datta, Geraldine Dawson, Richard Day, Eco J. De Geus, Franziska Degenhardt, Bernie Devlin, Srdjan Djurovic, Gary J. Donohoe, Alysa E. Doyle, Jubao Duan, Frank Dudbridge, Eftichia Duketis, Richard P. Ebstein, Howard J. Edenberg, Josephine Elia, Sean Ennis, Bruno Etain, Ayman Fanous, Stephen V. Faraone, Anne E. Farmer, I. Nicol Ferrier, Matthew Flickinger, Eric Fombonne, Tatiana Foroud, Josef Frank, Barbara Franke, Christine Fraser, Robert Freedman, Nelson B. Freimer, Christine M. Freitag, Marion Friedl, Louise Frisén, Louise Gallagher, Pablo V. Gejman, Lyudmila Georgieva, Elliot S. Gershon, Daniel H. Geschwind, Ina Giegling, Michael Gill, Scott D. Gordon, Katherine Gordon-Smith, Elaine K. Green, Tiffany A. Greenwood, Dorothy E. Grice, Magdalena Gross, Detelina Grozeva, Weihua Guan, Hugh Gurling, Lieuwe De Haan, Jonathan L. Haines, Hakon Hakonarson, Joachim Hallmayer, Steven P. Hamilton, Marian L. Hamshere, Thomas F. Hansen, Annette M. Hartmann, Martin Hautzinger, Andrew C. Heath, Anjali K. Henders, Stefan Herms, Ian B. Hickie, Maria Hipolito, Susanne Hoefels, Peter A. Holmans, Florian Holsboer, Witte J. Hoogendijk, Jouke-Jan Hottenga, Vanessa Hus, Andrés Ingason, Marcus Ising, Stéphane Jamain, Ian Jones, Lisa Jones, Anna K. Kähler, René S. Kahn, Radhika Kandaswamy, Matthew C. Keller, John R. Kelsoe, James L. Kennedy, Elaine Kenny, Lindsey Kent, Yunjung Kim, George K. Kirov, Sabine M. Klauck, Lambertus Klei, James A. Knowles, Martin A. Kohli, Daniel L. Koller, Bettina Konte, Ania Korszun, Lydia Krabbendam, Robert Krasucki, Jonna Kuntsi, Phoenix Kwan, Niklas Långström, Mark Lathrop, Jacob Lawrence, William B. Lawson, Marion Leboyer, David H. Ledbetter, Phil H. Lee, Todd Lencz, Klaus-Peter Lesch, Cathryn M. Lewis, Jun Li, Paul Lichtenstein, Jeffrey A. Lieberman, Dan-Yu Lin, Don H. Linszen, Chunyu Liu, Falk W. Lohoff, Sandra K. Loo, Catherine Lord, Jennifer K. Lowe, Susanne Lucae, Donald J. MacIntyre, Pamela A.F. Madden, Elena Maestrini, Patrik K.E. Magnusson, Pamela B. Mahon, Wolfgang Maier, Anil K. Malhotra, Shrikant M. Mane, Christa L. Martin, Nicholas G. Martin, Manuel Mattheisen, Keith Matthews, Morten Mattingsdal, Steven A. McCarroll, Kevin A. McGhee, James J. McGough, Patrick J. McGrath, Peter McGuffin, Melvin G. McInnis, Andrew McIntosh, Rebecca McKinney, Alan W. McLean, Francis J. McMahon, William M. McMahon, Andrew McQuillin, Helena Medeiros, Sarah E. Medland, Sandra Meier, Ingrid Melle, Fan Meng, Jobst Meyer, Christel M. Middeldorp, Lefkos Middleton, Vihra Milanova, Ana Miranda, Anthony P. Monaco, Grant W. Montgomery, Jennifer L. Moran, Daniel Moreno-De-Luca, Gunnar Morken, Derek W. Morris, Eric M. Morrow, Valentina Moskvina, Bryan J. Mowry, Pierandrea Muglia, Thomas W. Mühleisen, Bertram Müller-Myhsok, Michael Murtha, Richard M. Myers, Inez Myin-Germeys, Benjamin M. Neale, Stan F. Nelson, Caroline M. Nievergelt, Ivan Nikolov, Vishwajit Nimgaonkar, Willem A. Nolen, Markus M. Nöthen, John I. Nurnberger, Evaristus A. Nwulia, Dale R. Nyholt, Michael C. O’Donovan, Colm O’Dushlaine, Robert D. Oades, Ann Olincy, Guiomar Oliveira, Line Olsen, Roel A. Ophoff, Urban Osby, Michael J. Owen, Aarno Palotie, Jeremy R. Parr, Andrew D. Paterson, Carlos N. Pato, Michele T. Pato, Brenda W. Penninx, Michele L. Pergadia, Margaret A. Pericak-Vance, Roy H. Perlis, Benjamin S. Pickard, Jonathan Pimm, Joseph Piven, Danielle Posthuma, Fritz Poustka, Peter Propping, Shaun M. Purcell, Vinay Puri, Digby J. Quested, Emma M. Quinn, Josep Antoni Ramos-Quiroga, Henrik B. Rasmussen, Soumya Raychaudhuri, Karola Rehnström, Andreas Reif, Marta Ribasés, John P. Rice, Marcella Rietschel, Kathryn Roeder, Herbert Roeyers, Lizzy Rossin, Aribert Rothenberger, Guy Rouleau, Douglas Ruderfer, Dan Rujescu, Alan R. Sanders, Stephan J. Sanders, Susan L. Santangelo, Russell Schachar, Martin Schalling, Alan F. Schatzberg, Gerard D. Schellenberg, Stephen W. Scherer, Nicholas J. Schork, Thomas G. Schulze, Johannes Schumacher, Markus Schwarz, Edward Scolnick, Laura J. Scott, Joseph A. Sergeant, Paul D. Shilling, Stanley I. Shyn, Jeremy M. Silverman, Pamela Sklar, Susan L. Slager, Susan L. Smalley, Johannes H. Smit, Erin N. Smith, Edmund J.S. Sonuga-Barke, David St Clair, Matthew State, Michael Steffens, Hans-Christoph Steinhausen, John S. Strauss, Jana Strohmaier, T. Scott Stroup, Patrick F. Sullivan, James Sutcliffe, Peter Szatmari, Szabocls Szelinger, Anita Thapar, Srinivasa Thirumalai, Robert C. Thompson, Alexandre A. Todorov, Federica Tozzi, Jens Treutlein, Jung-Ying Tzeng, Manfred Uhr, Edwin J.C.G. van den Oord, Gerard Van Grootheest, Jim Van Os, Astrid M. Vicente, Veronica J. Vieland, John B. Vincent, Peter M. Visscher, Christopher A. Walsh, Thomas H. Wassink, Stanley J. Watson, Lauren A. Weiss, Thomas Werge, Thomas F. Wienker, Durk Wiersma, Ellen M. Wijsman, Gonneke Willemsen, Nigel Williams, A. Jeremy Willsey, Stephanie H. Witt, Wei Xu, Allan H. Young, Timothy W. Yu, Stanley Zammit, Peter P. Zandi, Peng Zhang, Frans G. Zitman, Sebastian Zöllner, University of Zurich, Lee, S Hong, Epidemiology and Data Science, Psychiatry, EMGO - Mental health, NCA - Neurobiology of mental health, Human genetics, NCA - Brain mechanisms in health and disease, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Maier, Robert, Moser, Gerhard, Chen, Guo-Bo, Ripke, Stephan, Coryell, William, Potash, James B, Scheftner, William A, Shi, Jianxin, Weissman, Myrna M, Hultman, Christina M, Landen, Mikael, Levinson, Douglas F, Kendler, Kenneth S, Smoller, Jordan, Wray, Naomi R, Cross-Disorder Working Group of the Psychiatric Genomics Consortium, Oades, Robert D. (Beitragende*r), Génétique de l'autisme = Genetics of Autism (NPS-01), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of St Andrews. School of Medicine, University of St Andrews. Institute of Behavioural and Neural Sciences, Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANS - Amsterdam Neuroscience, Adult Psychiatry, Child Psychiatry, Maier R., Moser G., Chen G.-B., Ripke S., Coryell W., Potash J.B., Scheftner W.A., Shi J., Weissman M.M., Hultman C.M., Landen M., Levinson D.F., Kendler K.S., Smoller J.W., Wray N.R., Lee S.H., Absher D., Agartz I., Akil H., Amin F., Andreassen O.A., Anjorin A., Anney R., Arking D.E., Asherson P., Azevedo M.H., Backlund L., Badner J.A., Bailey A.J., Banaschewski T., Barchas J.D., Barnes M.R., Barrett T.B., Bass N., Battaglia A., Bauer M., Bayes M., Bellivier F., Bergen S.E., Berrettini W., Betancur C., Bettecken T., Biederman J., Binder E.B., Black D.W., Blackwood D.H.R., Bloss C.S., Boehnke M., Boomsma D.I., Breen G., Breuer R., Bruggeman R., Buccola N.G., Buitelaar J.K., Bunney W.E., Buxbaum J.D., Byerley W.F., Caesar S., Cahn W., Cantor R.M., Casas M., Chakravarti A., Chambert K., Choudhury K., Cichon S., Robert Cloninger C., Collier D.A., Cook E.H., Coon H., Cormand B., Cormican P., Corvin A., Coryell W.H., Craddock N., Craig D.W., Craig I.W., Crosbie J., Cuccaro M.L., Curtis D., Czamara D., Daly M.J., Datta S., Dawson G., Day R., De Geus E.J., Degenhardt F., Devlin B., Djurovic S., Donohoe G.J., Doyle A.E., Duan J., Dudbridge F., Duketis E., Ebstein R.P., Edenberg H.J., Elia J., Ennis S., Etain B., Fanous A., Faraone S.V., Farmer A.E., Nicol Ferrier I., Flickinger M., Fombonne E., Foroud T., Frank J., Franke B., Fraser C., Freedman R., Freimer N.B., Freitag C.M., Friedl M., Frisen L., Gallagher L., Gejman P.V., Georgieva L., Gershon E.S., Geschwind D.H., Giegling I., Gill M., Gordon S.D., Gordon-Smith K., Green E.K., Greenwood T.A., Grice D.E., Gross M., Grozeva D., Guan W., Gurling H., De Haan L., Haines J.L., Hakonarson H., Hallmayer J., Hamilton S.P., Hamshere M.L., Hansen T.F., Hartmann A.M., Hautzinger M., Heath A.C., Henders A.K., Herms S., Hickie I.B., Hipolito M., Hoefels S., Holmans P.A., Holsboer F., Hoogendijk W.J., Hottenga J.-J., Hus V., Ingason A., Ising M., Jamain S., Jones I., Jones L., Kahler A.K., Kahn R.S., Kandaswamy R., Keller M.C., Kelsoe J.R., Kennedy J.L., Kenny E., Kent L., Kim Y., Kirov G.K., Klauck S.M., Klei L., Knowles J.A., Kohli M.A., Koller D.L., Konte B., Korszun A., Krabbendam L., Krasucki R., Kuntsi J., Kwan P., Langstrom N., Lathrop M., Lawrence J., Lawson W.B., Leboyer M., Ledbetter D.H., Lee P.H., Lencz T., Lesch K.-P., Lewis C.M., Li J., Lichtenstein P., Lieberman J.A., Lin D.-Y., Linszen D.H., Liu C., Lohoff F.W., Loo S.K., Lord C., Lowe J.K., Lucae S., MacIntyre D.J., Madden P.A.F., Maestrini E., Magnusson P.K.E., Mahon P.B., Maier W., Malhotra A.K., Mane S.M., Martin C.L., Martin N.G., Mattheisen M., Matthews K., Mattingsdal M., McCarroll S.A., McGhee K.A., McGough J.J., McGrath P.J., McGuffin P., McInnis M.G., McIntosh A., McKinney R., McLean A.W., McMahon F.J., McMahon W.M., McQuillin A., Medeiros H., Medland S.E., Meier S., Melle I., Meng F., Meyer J., Middeldorp C.M., Middleton L., Milanova V., Miranda A., Monaco A.P., Montgomery G.W., Moran J.L., Moreno-De-Luca D., Morken G., Morris D.W., Morrow E.M., Moskvina V., Mowry B.J., Muglia P., Muhleisen T.W., Muller-Myhsok B., Murtha M., Myers R.M., Myin-Germeys I., Neale B.M., Nelson S.F., Nievergelt C.M., Nikolov I., Nimgaonkar V., Nolen W.A., Nothen M.M., Nurnberger J.I., Nwulia E.A., Nyholt D.R., O'Donovan M.C., O'Dushlaine C., Oades R.D., Olincy A., Oliveira G., Olsen L., Ophoff R.A., Osby U., Owen M.J., Palotie A., Parr J.R., Paterson A.D., Pato C.N., Pato M.T., Penninx B.W., Pergadia M.L., Pericak-Vance M.A., Perlis R.H., Pickard B.S., Pimm J., Piven J., Posthuma D., Poustka F., Propping P., Purcell S.M., Puri V., Quested D.J., Quinn E.M., Ramos-Quiroga J.A., Rasmussen H.B., Raychaudhuri S., Rehnstrom K., Reif A., Ribases M., Rice J.P., Rietschel M., Roeder K., Roeyers H., Rossin L., Rothenberger A., Rouleau G., Ruderfer D., Rujescu D., Sanders A.R., Sanders S.J., Santangelo S.L., Schachar R., Schalling M., Schatzberg A.F., Schellenberg G.D., Scherer S.W., Schork N.J., Schulze T.G., Schumacher J., Schwarz M., Scolnick E., Scott L.J., Sergeant J.A., Shilling P.D., Shyn S.I., Silverman J.M., Sklar P., Slager S.L., Smalley S.L., Smit J.H., Smith E.N., Sonuga-Barke E.J.S., St Clair D., State M., Steffens M., Steinhausen H.-C., Strauss J.S., Strohmaier J., Scott Stroup T., Sullivan P.F., Sutcliffe J., Szatmari P., Szelinger S., Thapar A., Thirumalai S., Thompson R.C., Todorov A.A., Tozzi F., Treutlein J., Tzeng J.-Y., Uhr M., van den Oord E.J.C.G., Van Grootheest G., Van Os J., Vicente A.M., Vieland V.J., Vincent J.B., Visscher P.M., Walsh C.A., Wassink T.H., Watson S.J., Weiss L.A., Werge T., Wienker T.F., Wiersma D., Wijsman E.M., Willemsen G., Williams N., Jeremy Willsey A., Witt S.H., Xu W., Young A.H., Yu T.W., Zammit S., Zandi P.P., Zhang P., Zitman F.G., and Zollner S.

Subjects
Netherlands Twin Register (NTR), Multifactorial Inheritance, Multivariate analysis, Bipolar Disorder, genome annotation, Medizin, R Medicine (General), Medical and Health Sciences, Genome-wide association studies, 0302 clinical medicine, 2.5 Research design and methodologies (aetiology), GWAS, Genetics(clinical), Aetiology, Multivariate Analysi, Genetics (clinical), Genetics & Heredity, bipolar disorder, 0303 health sciences, education.field_of_study, Depression, Mental Disorders, Single Nucleotide, 3rd-DAS, Biological Sciences, 10058 Department of Child and Adolescent Psychiatry, Serious Mental Illness, Psychiatric Disorders, 3. Good health, Mental Health, Schizophrenia, Mental Disorder, Linear Model, Major depressive disorder, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Risk assessment, Human, medicine.medical_specialty, 2716 Genetics (clinical), Genetics, Medical, Population, SNP, 610 Medicine & health, QH426 Genetics, Best linear unbiased prediction, Polymorphism, Single Nucleotide, Risk Assessment, 03 medical and health sciences, 1311 Genetics, Medical, Report, medicine, Genetics, Humans, Bipolar disorder, Genetic Testing, Polymorphism, education, Psychiatry, QH426, 030304 developmental biology, Depressive Disorder, Depressive Disorder, Major, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, Cross-Disorder Working Group of the Psychiatric Genomics Consortium, Prevention, Human Genome, Major, medicine.disease, genetic risk prediction, R1, Brain Disorders, schizophrenia, Sample size determination, Perturbações do Desenvolvimento Infantil e Saúde Mental, Multivariate Analysis, Linear Models, business, depressive disorders, 030217 neurology & neurosurgery
Abstract

Cross-Disorder Working Group of the Psychiatric Genomics Consortium - Vicente A.M. Acessível em: http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25640677/ Genetic risk prediction has several potential applications in medical research and clinical practice and could be used, for example, to stratify a heterogeneous population of patients by their predicted genetic risk. However, for polygenic traits, such as psychiatric disorders, the accuracy of risk prediction is low. Here we use a multivariate linear mixed model and apply multi-trait genomic best linear unbiased prediction for genetic risk prediction. This method exploits correlations between disorders and simultaneously evaluates individual risk for each disorder. We show that the multivariate approach significantly increases the prediction accuracy for schizophrenia, bipolar disorder, and major depressive disorder in the discovery as well as in independent validation datasets. By grouping SNPs based on genome annotation and fitting multiple random effects, we show that the prediction accuracy could be further improved. The gain in prediction accuracy of the multivariate approach is equivalent to an increase in sample size of 34% for schizophrenia, 68% for bipolar disorder, and 76% for major depressive disorders using single trait models. Because our approach can be readily applied to any number of GWAS datasets of correlated traits, it is a flexible and powerful tool to maximize prediction accuracy. With current sample size, risk predictors are not useful in a clinical setting but already are a valuable research tool, for example in experimental designs comparing cases with high and low polygenic risk

Published
2015

26. Familial Association and Frequency of Learning Disabilities in ADHD Sibling Pair Families

Author

Tae S. Kim, Melissa Del’Homme, May H. Yang, Sandra K. Loo, and Susan L. Smalley

Subjects
Adult, Male, Reading disability, Adolescent, Writing, Developmental psychology, Interviews as Topic, mental disorders, Developmental and Educational Psychology, medicine, Humans, Family, Interpersonal Relations, Parent-Child Relations, Sibling, Child, Intelligence quotient, Learning Disabilities, Siblings, Wechsler Scales, Dyslexia, Wechsler Adult Intelligence Scale, Middle Aged, medicine.disease, Comorbidity, Psychiatry and Mental health, Reading, El Niño, Attention Deficit Disorder with Hyperactivity, Learning disability, Educational Status, Female, medicine.symptom, Psychology
Abstract

In a sample of 235 families with at least two children with Attention-Deficit/ Hyperactivity Disorder (ADHD), the frequency and familial association of learning disabilities (LD) were assessed. Familiality was examined both between sibling pairs and between parents and their children. Two methods for defining LD, a discrepancy-based and a low-achievement model, were employed to examine the occurrence of LD in this sample. The specific types of LD examined included Reading Disability (RD), Math Disability (MD), and Writing Disability (WD). The prevalence rates were highest for RD, followed by WD then MD. The two definitions of LD yielded similar prevalence rates but identified different groups of children with vastly different IQ scores. Strong familial association was demonstrated for RD both between sibling pairs and between parents and children, with weaker association for WD. There was evidence of nonrandom mating for LD among parents, but not for ADHD or for ADHD + LD. Despite the high comorbidity of ADHD and LD among parents, the presence of ADHD in the parents did not predict child LD supporting independent familial factors underlying ADHD and LD.

Published
2006

27. Relationship of Family Environment and Parental Psychiatric Diagnosis to Impairment in ADHD

Author

Erika M. Carpenter, Gitta H. Lubke, Sandra K. Loo, May H. Yang, Deborah E. Lynn, James J. McGough, James T. McCracken, Joan Rosenbaum Asarnow, Susan L. Smalley, and Leah J. Pressman

Subjects
Parents, Adolescent, Social Environment, Developmental psychology, Child of Impaired Parents, Surveys and Questionnaires, Interview, Psychological, Developmental and Educational Psychology, medicine, Humans, Family, Sibling, Family Environment Scale, Child, Mental Disorders, Siblings, Social environment, medicine.disease, Mental health, Comorbidity, Psychiatry and Mental health, Birth order, El Niño, Attention Deficit Disorder with Hyperactivity, Psychology, Psychopathology
Abstract

Objective Family environmental factors as well as parental attention-deficit/hyperactivity disorder (ADHD) status have shown associations with variability in ADHD. The purpose of the present study was to examine the links among family environment, parental psychiatric diagnosis, and child impairment within a sample of ADHD-affected sibling pairs (ASPs) ages 5 to 18 years. Method Parents in 220 ASP families completed a measure of family functioning, the Family Environment Scale. Children's impairment was measured by clinical ratings of global functioning and by maternal ratings of behavior. Results Parents of children with ADHD rate their families as higher in conflict and lower in achievement and organization than normative samples. High family conflict is significantly associated with impairment in ADHD ASPs accounting for ∼40% of the sibling similarity in impairment. Parental psychiatric diagnosis revealed no significant direct link to sibling impairment, but rather a significant indirect link to impairment mediated by family conflict. Direct associations with parental diagnosis depend on birth order of the ASP members despite the comparable mean impairment scores for older and younger ADHD siblings. Conclusions There are strong links between impairment in children with ADHD and family environment. Different processes and mechanisms may contribute to impairment in different children in the same family. J. Am. Acad. Child Adolesc. Psychiatry , 2006;45(3):346-354.

Published
2006

28. Impaired linguistic processing and atypical brain laterality in adults with ADHD

Author

Eran Zaidel, Joseph M. Phillips, Susan L. Smalley, James J. McGough, James T. McCracken, and T. Sigi Hale

Subjects
medicine.medical_specialty, education.field_of_study, Deep linguistic processing, Population, Cognition, Audiology, Lateralization of brain function, Functional imaging, Psychiatry and Mental health, Neuropsychology and Physiological Psychology, Neurology, Endophenotype, Laterality, Lexical decision task, medicine, Neurology (clinical), Psychology, education, Biological Psychiatry, Cognitive psychology
Abstract

Introduction: cognitive/behavioral testing, structural imaging, and functional imaging, has demonstrated atypical cerebral asymmetries in patients with attention-deficit/hyperactivity disorder (ADHD). However, few studies directly examined the nature of hemispheric specialization and interaction in this population. Methods: the present experiment applied techniques from behavioral laterality research to assess directly left/right brain dynamics in unmedicated adults with ADHD (n=21) and controls (n=22). We used a lateralized lexical decision task to assess hemispheric differences in word recognition and cross-callosal interhemispheric transfer of linguistic information. Results: analysis of variance indicated that ADHD subjects were impaired relative to controls in identifying words in both hemispheres (P=0.001). Furthermore, ADHD subjects exhibited decreased effects for ‘word regularity’ (P=004), enhanced effects of ‘word frequency’ (P=007), and an increased bias for ‘nonword’ responses overall (P=03), as well as during left visual field trials in particular (P=01). Conclusions: adult subjects with ADHD demonstrated poor linguistic processing. Group differences in sensitivity to semantic and phonological linguistic variables, along with differences in response biases, suggested that ADHD subjects had reduced left hemisphere and enhanced right hemisphere involvement during our task. These findings are relevant to current research investigating ‘endophenotypes’ in ADHD, as laterality indices may prove useful in etiological research, particularly molecular genetic investigations, and highlights the relevance of brain laterality research in clinical psychiatry.

Published
2005

29. Toward localizing genes underlying cerebral asymmetry and mental health

Author

Susan L. Smalley, Sandra K. Loo, Rita M. Cantor, and May H. Yang

Subjects
Genetic Linkage, Specific language impairment, Biology, behavioral disciplines and activities, Functional Laterality, Dyslexia, Cellular and Molecular Neuroscience, Genetic linkage, mental disorders, medicine, Humans, Attention deficit hyperactivity disorder, Genetic Predisposition to Disease, Language disorder, Autistic Disorder, Sibling, Genetics (clinical), Genetics, Chromosomes, Human, Pair 13, Genome, Human, Siblings, Brain, Chromosome Mapping, medicine.disease, Developmental disorder, Psychiatry and Mental health, Mental Health, Attention Deficit Disorder with Hyperactivity, Chromosomes, Human, Pair 2, Chromosomes, Human, Pair 5, Autism, Chromosomes, Human, Pair 9, Chromosomes, Human, Pair 16, Chromosomes, Human, Pair 7, Chromosomes, Human, Pair 17
Abstract

Genome investigations of autism, attention deficit hyperactivity disorder (ADHD), and dyslexia suggest possible genetic overlap. Atypical cerebral asymmetry (ACA), the absence of the left hemisphere dominance for language, may be a shared phenotype due to genes located in regions of overlap. A binomal test is used to evaluate whether linked regions overlap more than expected by chance for 15 genome-wide scans in autism, ADHD, and dyslexia. Significant evidence of linkage overlap (P = 10−7) is seen for autism, ADHD, and dyslexia for seven chromosomal regions (2p11–12, 5p13, 7q22–33, 9q33–34, 13q22, 16p13, and 17p11–q11). Linkage analysis of ACA and molecular markers for 270 sibling pairs with ADHD is conducted using the Haseman–Elston statistic. Linkage analysis supports ACA as a shared phenotype with risk genes located on 9q33–34 or 16p13 (P

Published
2005

30. Attention Deficit Hyperactivity Disorder: Fine Mapping Supports Linkage to 5p13, 6q12, 16p13, and 17p11

Author

Sandra K. Loo, Janeen Ishii, James J. McGough, Matthew N. Ogdie, James T. McCracken, Stanley F. Nelson, Clyde Francks, May Yang, Simon E. Fisher, Susan L. Smalley, and Rita M. Cantor

Subjects
Genetic Markers, Population sample, Susceptibility gene, Biology, Genetic determinism, Gene mapping, Genetic linkage, Report, medicine, Genetics, Attention deficit hyperactivity disorder, Humans, Genetics(clinical), Genetics (clinical), Lod score, Linkage (software), Siblings, Chromosome Mapping, medicine.disease, Attention Deficit Disorder with Hyperactivity, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 6, Lod Score, Chromosomes, Human, Pair 16, Chromosomes, Human, Pair 17
Abstract

We completed fine mapping of nine positional candidate regions for attention-deficit/hyperactivity disorder (ADHD) in an extended population sample of 308 affected sibling pairs (ASPs), constituting the largest linkage sample of families with ADHD published to date. The candidate chromosomal regions were selected from all three published genomewide scans for ADHD, and fine mapping was done to comprehensively validate these positional candidate regions in our sample. Multipoint maximum LOD score (MLS) analysis yielded significant evidence of linkage on 6q12 (MLS 3.30; empiric P=.024) and 17p11 (MLS 3.63; empiric P=.015), as well as suggestive evidence on 5p13 (MLS 2.55; empiric P=.091). In conjunction with the previously reported significant linkage on the basis of fine mapping 16p13 in the same sample as this report, the analyses presented here indicate that four chromosomal regions--5p13, 6q12, 16p13, and 17p11--are likely to harbor susceptibility genes for ADHD. The refinement of linkage within each of these regions lays the foundation for subsequent investigations using association methods to detect risk genes of moderate effect size.

Published
2004
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31. Internet Treatment Delivery of Parent-Adolescent Conflict Training for Families with an ADHD Teen: A Feasibility Study

Author

Michael Marina, Erika M. Carpenter, Fred Frankel, Naihua Duan, and Susan L. Smalley

Subjects
Psychotherapist, business.industry, education, Pact, medicine.disease, Training (civil), GeneralLiterature_MISCELLANEOUS, Developmental psychology, Clinical Psychology, Treatment delivery, mental disorders, medicine, Parent training, Attention deficit hyperactivity disorder, Web application, Confidentiality, The Internet, Psychology, business, Social Sciences (miscellaneous)
Abstract

The present study examines the feasibility of Internet delivery of a Parent-Adolescent Conflict Training (PACT) program to families with an ADHD teen. The goals of the project are to ascertain the ...

Published
2004

32. Joint Analysis of the DRD5 Marker Concludes Association with Attention-Deficit/Hyperactivity Disorder Confined to the Predominantly Inattentive and Combined Subtypes

Author

Harvey Wickham, Michael Gill, Christopher J. Kratochvil, Ziarih Hawi, Richard P. Ebstein, Iris Manor, Eda Tahir, Philip Asherson, Jonathan Mill, Yanke Yazgan, Stan F. Nelson, Anita Thapar, Aiveen Kirley, Richard J. Sinke, Shelley D. Smith, Antony Payton, Tatiana Roman, Susan L. Smalley, Florence Levy, Karen Wigg, Timothy Stephens, F. Middle, Stephen V. Faraone, Jan K. Buitelaar, Lindsey Kent, Pak C. Sham, Luis Augusto Rohde, Cathy L. Barr, Richard D. Todd, N. Lowe, Saretta Y. Lee, and Joseph Biederman

Subjects
Genetic Markers, Male, Proband, Locus (genetics), Impulsivity, 03 medical and health sciences, 0302 clinical medicine, Cognitive neurosciences [UMCN 3.2], Report, Genotype, Odds Ratio, Determinants in Health and Disease [EBP 1], Genetics, Humans, Medicine, Attention deficit hyperactivity disorder, Genetics(clinical), Allele, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Genetics (clinical), 030304 developmental biology, Psychiatry, 0303 health sciences, business.industry, Odds ratio, medicine.disease, Attention Deficit Disorder with Hyperactivity, Etiology, Female, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

PUBLISHED, PMID: 14732906, Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable, heterogeneous disorder of early onset, consisting of a triad of symptoms: inattention, hyperactivity, and impulsivity. The disorder has a significant genetic component, and theories of etiology include abnormalities in the dopaminergic system, with DRD4, DAT1, SNAP25, and DRD5 being implicated as major susceptibility genes. An initial report of association between ADHD and the common 148-bp allele of a microsatellite marker located 18.5 kb from the DRD5 gene has been followed by several studies showing nonsignificant trends toward association with the same allele. To establish the postulated association of the (CA)n repeat with ADHD, we collected genotypic information from 14 independent samples of probands and their parents, analyzed them individually and, in the absence of heterogeneity, analyzed them as a joint sample. The joint analysis showed association with the DRD5 locus (P=.00005; odds ratio 1.24; 95% confidence interval 1.12?1.38). This association appears to be confined to the predominantly inattentive and combined clinical subtypes., Health Research Board

Published
2004
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33. Proton magnetic resonance spectroscopic imaging of the brain in childhood autism

Author

Donald Guthrie, James T. McCracken, Susan L. Smalley, Jennifer G. Levitt, Joseph O'Neill, Rebecca E. Blanton, David Fadale, Arthur W. Toga, and Jeffrey R. Alger

Subjects
Male, Cingulate cortex, medicine.medical_specialty, Adolescent, Intelligence, Caudate nucleus, Tritium, Creatine, Choline, Phosphocreatine, chemistry.chemical_compound, Internal medicine, Cortex (anatomy), medicine, Humans, Autistic Disorder, Child, Biological Psychiatry, Aspartic Acid, Brain Mapping, medicine.diagnostic_test, Brain, Spectrometry, X-Ray Emission, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, Developmental disorder, Endocrinology, medicine.anatomical_structure, chemistry, Case-Control Studies, Child, Preschool, Autism, Female, Psychology, Neuroscience
Abstract

Background Autism is a developmental disorder of unknown neurologic basis. Based on prior work, we used proton magnetic resonance spectroscopic imaging (1H- MRSI) to investigate brain structures, including cingulate and caudate, that we hypothesized would reveal metabolic abnormalities in subjects with autism. Methods In 22 children with autism, 5 to 16 years old, and 20 age-matched healthy control subjects, 1H-MRSI assessed levels of N-acetyl compounds (NAA), choline compounds (Cho), and creatine plus phosphocreatine (Cr) at 272 msec echo-time and 1.5 T. Results In subjects with autism compared with control subjects, Cho was 27.2% lower in left inferior anterior cingulate and 19.1% higher in the head of the right caudate nucleus; Cr was 21.1% higher in the head of the right caudate nucleus, but lower in the body of the left caudate nucleus (17.9%) and right occipital cortex (16.6%). Conclusions Results are consistent with altered membrane metabolism, altered energetic metabolism, or both in the left anterior cingulate gyrus, both caudate nuclei, and right occipital cortex in subjects with autism compared with control subjects.

Published
2003

34. Genome-wide scan of reading ability in affected sibling pairs with attention-deficit/hyperactivity disorder: unique and shared genetic effects

Author

Simon E. Fisher, Stan F. Nelson, May Yang, Anthony P. Monaco, Sandra K. Loo, I L MacPhie, Matthew N. Ogdie, James T. McCracken, Susan L. Smalley, Clyde Francks, and James J. McGough

Subjects
Male, Reading disability, Adolescent, Genetic Linkage, Quantitative Trait Loci, Comorbidity, Quantitative trait locus, Genetic determinism, Developmental psychology, Dyslexia, Cellular and Molecular Neuroscience, Quantitative Trait, Heritable, Genetic linkage, Communication disorder, medicine, Chromosomes, Human, Humans, Attention deficit hyperactivity disorder, Computer Simulation, Genetic Predisposition to Disease, Sibling, Child, Molecular Biology, Genetics, Models, Genetic, Genome, Human, Siblings, medicine.disease, Psychiatry and Mental health, Reading, Attention Deficit Disorder with Hyperactivity, Child, Preschool, Female, Psychology
Abstract

Attention-deficit/hyperactivity disorder (ADHD) and reading disability (RD) are common highly heritable disorders of childhood, which frequently co-occur. Data from twin and family studies suggest that this overlap is, in part, due to shared genetic underpinnings. Here, we report the first genome-wide linkage analysis of measures of reading ability in children with ADHD, using a sample of 233 affected sibling pairs who previously participated in a genome-wide scan for susceptibility loci in ADHD. Quantitative trait locus (QTL) analysis of a composite reading factor defined from three highly correlated reading measures identified suggestive linkage (multipoint maximum lod score, MLS>2.2) in four chromosomal regions. Two regions (16p, 17q) overlap those implicated by our previous genome-wide scan for ADHD in the same sample: one region (2p) provides replication for an RD susceptibility locus, and one region (10q) falls approximately 35 cM from a modestly highlighted region in an independent genome-wide scan of siblings with ADHD. Investigation of an individual reading measure of Reading Recognition supported linkage to putative RD susceptibility regions on chromosome 8p (MLS=2.4) and 15q (MLS=1.38). Thus, the data support the existence of genetic factors that have pleiotropic effects on ADHD and reading ability--as suggested by shared linkages on 16p, 17q and possibly 10q--but also those that appear to be unique to reading--as indicated by linkages on 2p, 8p and 15q that coincide with those previously found in studies of RD. Our study also suggests that reading measures may represent useful phenotypes in ADHD research. The eventual identification of genes underlying these unique and shared linkages may increase our understanding of ADHD, RD and the relationship between the two.

Published
2003

35. Genetic Linkage of Attention-Deficit/Hyperactivity Disorder on Chromosome 16p13, in a Region Implicated in Autism

Author

Clyde Francks, I. Laurence MacPhie, Sonia L. Minassian, Simon E. Fisher, Jennifer Stone, Matthew N. Ogdie, James T. McCracken, Stanley F. Nelson, James J. McGough, Susan L. Smalley, Vlad Kustanovich, Rita M. Cantor, and Anthony P. Monaco

Subjects
Male, Genetic Linkage, Biology, Genetic determinism, 03 medical and health sciences, 0302 clinical medicine, Genetic linkage, Report, mental disorders, medicine, Genetics, Attention deficit hyperactivity disorder, Humans, 0501 psychology and cognitive sciences, Genetics(clinical), Allele, Autistic Disorder, Genetics (clinical), 05 social sciences, Chromosome, Chromosome Mapping, medicine.disease, Developmental disorder, Attention Deficit Disorder with Hyperactivity, Autism, Female, 030217 neurology & neurosurgery, Chromosomes, Human, Pair 16, 050104 developmental & child psychology, Psychopathology
Abstract

Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed behavioral disorder in childhood and likely represents an extreme of normal behavior. ADHD significantly impacts learning in school-age children and leads to impaired functioning throughout the life span. There is strong evidence for a genetic etiology of the disorder, although putative alleles, principally in dopamine-related pathways suggested by candidate-gene studies, have very small effect sizes. We use affected-sib-pair analysis in 203 families to localize the first major susceptibility locus for ADHD to a 12-cM region on chromosome 16p13 (maximum LOD score 4.2; P=.000005), building upon an earlier genomewide scan of this disorder. The region overlaps that highlighted in three genome scans for autism, a disorder in which inattention and hyperactivity are common, and physically maps to a 7-Mb region on 16p13. These findings suggest that variations in a gene on 16p13 may contribute to common deficits found in both ADHD and autism.

Published
2002
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36. A Genomewide Scan for Loci Involved in Attention-Deficit/Hyperactivity Disorder

Author

Stanley F. Nelson, Lori Crawford, Anthony P. Monaco, Dianne F. Newbury, Simon E. Fisher, Christina G.S. Palmer, Susan L. Smalley, Dennis P. Cantwell, J. Arthur Woodward, James J. McGough, Melissa Del’Homme, Angela J. Marlow, Clyde Francks, I. Laurence MacPhie, and James T. McCracken

Subjects
Male, Candidate gene, Genotype, Biology, Quantitative trait locus, Genetic determinism, 03 medical and health sciences, Quantitative Trait, Heritable, 0302 clinical medicine, Ethnicity, medicine, Genetics, Chromosomes, Human, Humans, Attention deficit hyperactivity disorder, Genetics(clinical), Autistic Disorder, Allele, Alleles, Genetics (clinical), X chromosome, 030304 developmental biology, Linkage (software), 0303 health sciences, Genome, Human, Racial Groups, Chromosome Mapping, Articles, medicine.disease, Major gene, Attention Deficit Disorder with Hyperactivity, Female, Lod Score, 030217 neurology & neurosurgery, Microsatellite Repeats
Abstract

Attention deficit/hyperactivity disorder (ADHD) is a common heritable disorder with a childhood onset. Molecular genetic studies of ADHD have previously focused on examining the roles of specific candidate genes, primarily those involved in dopaminergic pathways. We have performed the first systematic genomewide linkage scan for loci influencing ADHD in 126 affected sib pairs, using a approximately 10-cM grid of microsatellite markers. Allele-sharing linkage methods enabled us to exclude any loci with a lambda(s) of > or =3 from 96% of the genome and those with a lambda(s) of > or =2.5 from 91%, indicating that there is unlikely to be a major gene involved in ADHD susceptibility in our sample. Under a strict diagnostic scheme we could exclude all screened regions of the X chromosome for a locus-specific lambda(s) of >/=2 in brother-brother pairs, demonstrating that the excess of affected males with ADHD is probably not attributable to a major X-linked effect. Qualitative trait maximum LOD score analyses pointed to a number of chromosomal sites that may contain genetic risk factors of moderate effect. None exceeded genomewide significance thresholds, but LOD scores were >1.5 for regions on 5p12, 10q26, 12q23, and 16p13. Quantitative-trait analysis of ADHD symptom counts implicated a region on 12p13 (maximum LOD 2.6) that also yielded a LOD >1 when qualitative methods were used. A survey of regions containing 36 genes that have been proposed as candidates for ADHD indicated that 29 of these genes, including DRD4 and DAT1, could be excluded for a lambda(s) of 2. Only three of the candidates-DRD5, 5HTT, and CALCYON-coincided with sites of positive linkage identified by our screen. Two of the regions highlighted in the present study, 2q24 and 16p13, coincided with the top linkage peaks reported by a recent genome-scan study of autistic sib pairs.

Published
2002
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37. Community-Based Mindfulness Program for Disease Prevention and Health Promotion: Targeting Stress Reduction

Author

M. Jennifer Kitil, David StC. Black, Brian M. Galla, Gillian A. O’Reilly, and Susan L. Smalley

Subjects
Gerontology, Adult, Male, Stress management, medicine.medical_specialty, Health (social science), Mindfulness, Health Promotion, Nursing, Intervention (counseling), medicine, Humans, Public health, Multilevel model, Public Health, Environmental and Occupational Health, Middle Aged, Los Angeles, Test (assessment), Health promotion, Meditation, Community health, Female, Empathy, Psychology, Stress, Psychological
Abstract

Purpose. Poorly managed stress leads to detrimental physical and psychological consequences that have implications for individual and community health. Evidence indicates that U.S. adults predominantly use unhealthy strategies for stress management. This study examines the impact of a community-based mindfulness training program on stress reduction. Design. This study used a one-group pretest-posttest design. Setting. The study took place at the UCLA Mindful Awareness Research Center in urban Los Angeles. Subjects. A sample of N = 127 community residents (84% Caucasian, 74% female) were included in the study. Intervention. Participants received mindfulness training through the Mindful Awareness Practices (MAPs) for Daily Living I. Measures. Mindfulness, self-compassion, and perceived stress were measured at baseline and postintervention. Analysis. Paired-sample t-tests were used to test for changes in outcome measures from baseline to postintervention. Hierarchical regression analysis was fit to examine whether change in self-reported mindfulness and self-compassion predicted postintervention perceived stress scores. Results. There were statistically significant improvements in self-reported mindfulness (t = −10.67, p < .001, d = .90), self-compassion (t = −8.50, p < .001, d = .62), and perceived stress (t = 9.28, p < .001, d = –.78) at postintervention. Change in self-compassion predicted postintervention perceived stress (β = –.44, t = −5.06, p < .001), but change in mindfulness did not predict postintervention perceived stress (β = –.04, t = –.41, p = .68). Conclusion. These results indicate that a community-based mindfulness training program can lead to reduced levels of psychological stress. Mindfulness training programs such as MAPs may offer a promising approach for general public health promotion through improving stress management in the urban community.

Published
2014

38. Genetic variation associated with euphorigenic effects of d-amphetamine is associated with diminished risk for schizophrenia and attention deficit hyperactivity disorder

Author

Robert D. Oades, Andreas Reif, Lindsey Kent, Abraham A. Palmer, Barbara E. Engelhardt, Amy B. Hart, Tobias Banaschewski, Josep Antoni Ramos-Quiroga, Bru Cormand, Josephine Elia, P. Asherson, Anita Thapar, Joseph Biederman, Neale Bm, J. J. McGough, Eric R. Gamazon, Edmund Sonuga-Barke, Nancy J. Cox, Russell Schachar, Pamela Sklar, Christina M. Hultman, Anna K. Kähler, Nigel Williams, Susan L. Smalley, Jennifer Crosbie, H. de Wit, Stan F. Nelson, Patrick F. Sullivan, Hans-Christoph Steinhausen, Mònica Bayés, S. E. Medland, Sandra K. Loo, Barbara Franke, Stephen V. Faraone, M. Ribasés, Jan K. Buitelaar, M. Casas, Aribert Rothenberger, Benjamin M. Neale, K.P. Lesch, Richard Anney, Alysa E. Doyle, Jonna Kuntsi, University of Zurich, and Palmer, Abraham A

Subjects
medicine.medical_specialty, Bipolar Disorder, Dextroamphetamine, medicine.medical_treatment, Medizin, 610 Medicine & health, Protective Agents, behavioral disciplines and activities, Polymorphism, Single Nucleotide, Euphoriant, Risk Factors, mental disorders, medicine, ddc:61, Humans, Attention deficit hyperactivity disorder, Genetic Predisposition to Disease, ddc:610, Medizinische Fakultät » Universitätsklinikum Essen » LVR-Klinikum Essen » Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters, Bipolar disorder, Psychiatry, Amphetamine, 1000 Multidisciplinary, Multidisciplinary, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Genetic Variation, Reproducibility of Results, Euphoria, Biological Sciences, 10058 Department of Child and Adolescent Psychiatry, medicine.disease, Stimulant, Phenotype, Attention Deficit Disorder with Hyperactivity, Schizophrenia, Endophenotype, Immunology, Psychology, medicine.drug
Abstract

Item does not contain fulltext Here, we extended our findings from a genome-wide association study of the euphoric response to d-amphetamine in healthy human volunteers by identifying enrichment between SNPs associated with response to d-amphetamine and SNPs associated with psychiatric disorders. We found that SNPs nominally associated (P

Published
2014

39. Randomised controlled pilot trial of mindfulness training for stress reduction during pregnancy

Author

Christine M. Guardino, Christine Dunkel Schetter, Michael C. Lu, Julienne E. Bower, and Susan L. Smalley

Subjects
and promotion of well-being, Mindfulness, mindfulness, 6.6 Psychological and behavioural, Psychological intervention, Pilot Projects, Reproductive health and childbirth, Anxiety, law.invention, Randomized controlled trial, law, Pregnancy, Psychology, Meditation, Applied Psychology, media_common, General Medicine, Clinical Psychology, Mental Health, Treatment Outcome, Female, Worry, medicine.symptom, Clinical psychology, Adult, meditation, media_common.quotation_subject, Clinical Trials and Supportive Activities, Stress, Article, Complementary and Alternative Medicine, Clinical Research, Intervention (counseling), Behavioral and Social Science, Complementary and Integrative Health, medicine, Humans, Prevention, Public Health, Environmental and Occupational Health, Evaluation of treatments and therapeutic interventions, General Chemistry, medicine.disease, Prevention of disease and conditions, prenatal stress, pregnancy anxiety, Psychological, 3.1 Primary prevention interventions to modify behaviours or promote wellbeing, Pregnant Women, 3.1 Primary prevention interventions to modify behaviours or promote well-being, Mind and Body, Curriculum and Pedagogy, Stress, Psychological, Follow-Up Studies
Abstract

This randomised controlled pilot trial tested a six-week mindfulness-based intervention in a sample of pregnant women experiencing high levels of perceived stress and pregnancy anxiety. Forty-seven women enrolled between 10 and 25 weeks gestation were randomly assigned to either a series of weekly Mindful Awareness Practices classes (n = 24) with home practice or to a reading control condition (n = 23). Hierarchical linear models of between-group differences in change over time demonstrated that participants in the mindfulness intervention experienced larger decreases from pre-to post-intervention in pregnancy-specific anxiety and pregnancy-related anxiety (PRA) than participants in the reading control condition. However, these effects were not sustained through follow-up at six weeks post-intervention. Participants in both groups experienced increased mindfulness, as well as decreased perceived stress and state anxiety over the course of the intervention and follow-up periods. This study is one of the first randomised controlled pilot trials of a mindfulness meditation intervention during pregnancy and provides some evidence that mindfulness training during pregnancy may effectively reduce PRA and worry. We discuss some of the dilemmas in pursuing this translational strategy and offer suggestions for researchers interested in conducting mind-body interventions during pregnancy. © 2013 © 2013 Taylor & Francis.

Published
2013

40. Macrocephaly in autism and other pervasive developmental disorders

Author

Julia N. Bailey, Deborah J. Fidler, and Susan L. Smalley

Subjects
Adult, Male, Proband, medicine.medical_specialty, Adolescent, Audiology, Age and sex, Tuberous sclerosis, Developmental Neuroscience, Risk Factors, Seizures, Tuberous Sclerosis, medicine, Humans, Autistic Disorder, Child, Anthropometry, Incidence (epidemiology), Macrocephaly, medicine.disease, Familial risk factor, Pedigree, Seizure Disorders, Pediatrics, Perinatology and Child Health, Autism, Female, Neurology (clinical), medicine.symptom, Psychology, Head
Abstract

To assess the prevalence of macrocephaly (head circumference [ges ]1.88 standard deviations above normative data for age and sex or >97th centile) in autism and other pervasive developmental disorders, 41 children with autism, and a comparison group of 21 children with tuberous sclerosis complex (TSC) or an unspecified seizure disorder were studied. Familiality of head circumference was also assessed from measurements of 133 first-degree relatives. Significantly higher rates of macrocephaly were found in probands with autism (12.2%) and their first-degree relatives (15.5%) when compared against a published normative sample. The incidence of macrocephaly in the comparison group of probands with TSC and seizure disorder (9.5%) and their first-degree relatives (8.3%) was higher than normative data as well, although the relation between macrocephaly and autism was more pronounced. Head circumference and extreme scores reflecting macrocephaly were moderately heritable in the present sample (H2=0.47). The increased prevalence of macrocephaly in relatives of children with autism compared with control children suggests that this characteristic may be a familial risk factor in the pathogenesis of autism.

Published
2000

41. No evidence of linkage or linkage disequilibrium between DAT1 and attention deficit hyperactivity disorder in a large sample

Author

Joan Rosenbaum Asarnow, J. A. Woodward, Christina G.S. Palmer, Dennis P. Cantwell, Melissa Del’Homme, James J. McGough, Susan L. Smalley, C. Ramsey, Stan F. Nelson, Janet S. Sinsheimer, Robert F. Asarnow, and Julia N. Bailey

Subjects
Male, Linkage disequilibrium, Bipolar Disorder, Genetic Linkage, Nerve Tissue Proteins, California, Linkage Disequilibrium, White People, Genetics, Humans, Medicine, Attention deficit hyperactivity disorder, Family, Child, Biological Psychiatry, Genetics (clinical), Linkage (software), Dopamine Plasma Membrane Transport Proteins, Membrane Glycoproteins, Mood Disorders, business.industry, Membrane Transport Proteins, medicine.disease, Large sample, Psychiatry and Mental health, Attention Deficit Disorder with Hyperactivity, Female, Carrier Proteins, business
Published
1999

42. Sixth World Congress of Psychiatric Genetics X chromosome workshop

Author

Nadine Norton, Ole Mors, Douglas F. Levinson, Hiroshi Kunugi, Sabine M. Klauck, Iiris Hovatta, Charles A. Kaufmann, Dirk Goossens, Lynn E. DeLisi, PV Gejman, Andrew D. Paterson, Stephen V. Faraone, and Susan L. Smalley

Subjects
Linkage (software), medicine.medical_specialty, medicine.disease, Developmental disorder, Schizophrenia, medicine, Attention deficit hyperactivity disorder, Autism, Bipolar disorder, Psychology, Psychiatry, Genetics (clinical), X chromosome, Psychiatric genetics
Abstract

At the X chromosome workshop of the Sixth World Congress on Psychiatric Genetics, new data regarding psychiatric phenotypes and the X chromosome were presented. In the last year a number of groups have published linkage results for the X chromosome in schizophrenia, which provide no significant evidence for linkage. Presentations by groups from Cardiff, Oxford, State University of New York (SUNY), and Finland provide weak nonsignificant evidence for linkage of markers on the Xp11.4-p11.3, Xq21, and Xq26 with schizophrenia. However, the presence of a male-specific transmission ratio distorter (DMS1) that maps to Xp11.4-21.2 [Naumova et al., 1998: Am. J. Hum. Genet. 62:1493-1499] makes the interpretation of linkage findings in brother-brother pairs difficult in this region. Regarding bipolar affective disorder, little new data were reported, but previous reports provide evidence for linkage to Xq25-q26. Summary tables of linkage results for schizophrenia and bipolar disorder can be obtained from http://www.camh.net/ research/x-chromosome/. No linkage or transmission disequilibrium of polymorphisms of MAOA and MAOB in attention deficit hyperactivity disorder was seen. Negative results for transmission disequilibrium of polymorphisms of HTR2C and MAOA with autism were provided from German and Austrian families.

Published
1999

43. Search for a gene×environment interaction: G×E hunt

Author

Susan L. Smalley, Janet S. Sinsheimer, Julia N. Bailey, and Marc A. Suchard

Subjects
Genetics, Affected sibling, Epidemiology, Genetic marker, Genetic linkage, Simulated data, Allele, Biology, Gene, Genome, Genetics (clinical)
Abstract

We developed a method to identify gene x environment interactions (G x Es). To test this method in the simulated data (Problem 2, GAW11), we first identified an environmental factor (E1) that was associated with the simulated disorder. We stratified affected sibling pairs (ASPs) into two groups, those concordant for the presence of E1 and those concordant for the absence of E1. We then localized genes on chromosomes 3 and 5 using identity-by-descent (IBD) sharing rates among ASPs. Because the stratified IBD sharing rates are independent of the environmental factor if there is no G x E, we inferred the existence of a G x E near loci 3G44 and 3G45 by testing whether the proportion of ASPs sharing no alleles IBD differed among the two groups.

Published
1999

44. Evidence that the dopamine D4 receptor is a susceptibility gene in attention deficit hyperactivity disorder

Author

Dennis P. Cantwell, C. Ramsey, Melissa Del’Homme, J. A. Woodward, Joan Rosenbaum Asarnow, Julia N. Bailey, Susan L. Smalley, Christina G.S. Palmer, James J. McGough, and Stan F. Nelson

Subjects
Genetics, medicine.medical_specialty, School age child, Susceptibility gene, medicine.disease, Genetic determinism, Cellular and Molecular Neuroscience, Psychiatry and Mental health, Endocrinology, Dopamine, Internal medicine, medicine, Attention deficit hyperactivity disorder, Psychology, Receptor, Molecular Biology, medicine.drug
Abstract

Evidence that the dopamine D4 receptor is a susceptibility gene in attention deficit hyperactivity disorder

Published
1998

45. [Untitled]

Author

Peter E. Tanguay, Griselda Gutierrez, and Susan L. Smalley

Subjects
Proband, congenital, hereditary, and neonatal diseases and abnormalities, medicine.disease, behavioral disciplines and activities, nervous system diseases, Substance abuse, Developmental disorder, Tuberous sclerosis, El Niño, mental disorders, Developmental and Educational Psychology, medicine, Pervasive developmental disorder, Autism, Risk factor, Psychology, neoplasms, Clinical psychology
Abstract

The frequency and clinical presentation of autism in 28 probands with tuberous sclerosis complex (TSC) are reported and risk factors that may influence the development of autism in TSC are examined. Eight probands meet ICD-10 and DSM-IV criteria for autism, an additional 4 meet criteria for pervasive developmental disorder (PDD). Twelve TSC probands with autism/PDD are compared to 16 TSC probands without these conditions for factors which may underlie the association of autism and TSC. A specific seizure type, infantile spasms, as well as mental retardation, are increased in the TSC, autistic/PDD group. Furthermore, rates of social phobia and substance abuse are elevated among first-degree relatives of TSC probands with autism compared to first-degree relatives of TSC probands without autism. Implications of these findings in understanding the association of autism and TSC are discussed.

Published
1998

46. A multivariate approach to affected-sib-pair analysis using highly dense molecular maps

Author

J. Arthur Woodward, Christina G.S. Palmer, Julia N. Bailey, and Susan L. Smalley

Subjects
Data set, Multivariate statistics, Epidemiology, business.industry, Statistics, False positive paradox, Pattern recognition, Artificial intelligence, Biology, business, Sib pairs, Genetics (clinical)
Abstract

A multivariate approach to affected-sib-pair analyses was performed to localize disease-susceptibility genes with a minimum number of type I errors (false positives). Using 1,155 independent affected sib pairs extracted from Problem 2A of the GAW10 data set, we were able to localize major genes (MG) 1 and 2. Using 30% of the affected-sib-pair sample (N = 337) we were able to localize MG1. False positives were not detected in either of these samples.

Published
1997

47. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

Author

Laura J. Scott, Bernie Devlin, Steven A. McCarroll, James S. Sutcliffe, Stefan Herms, Yunjung Kim, Richard O. Day, Thomas F. Wienker, Frank Dudbridge, I. Nicol Ferrier, Bettina Konte, Marta Ribasés, C. Robert Cloninger, Brenda W.J.H. Penninx, Detelina Grozeva, Herbert Roeyers, Peter Holmans, Colm O'Dushlaine, Scott D. Gordon, Sarah E. Bergen, Fan Meng, Morten Mattingsdal, Hugh Gurling, Ina Giegling, Gerard van Grootheest, Ania Korszun, Markus J. Schwarz, George Kirov, Sebastian Zöllner, Kenneth S. Kendler, Nicholas G. Martin, Michael Conlon O'Donovan, Michael C. Neale, Jim van Os, Aravinda Chakravarti, Timothy W. Yu, Mikael Landén, Inez Myin-Germeys, Markus M. Nöthen, Kathryn Roeder, James B. Potash, Alan W. McLean, Louise Gallagher, Anna K. Kähler, Thomas Bettecken, Nigel Williams, Frank Bellivier, Joseph D. Buxbaum, Derek W. Morris, Susan L. Smalley, Jung-Ying Tzeng, Martin Schalling, Douglas M. Ruderfer, Caroline M. Nievergelt, T. Scott Stroup, David H. Ledbetter, Jennifer Crosbie, Anita Thapar, Barbara Franke, Jeffrey A. Lieberman, Huda Akil, Miguel Casas, Daniel H. Geschwind, Paul Cormican, Bertram Müller-Myhsok, Lyudmila Georgieva, Robert Krasucki, Martin Hautzinger, Alysa E. Doyle, Cinnamon S. Bloss, Gerard D. Schellenberg, Todd Lencz, Melvin G. McInnis, Catalina Betancur, Josep Antoni Ramos-Quiroga, Stephen Sanders, Eftichia Duketis, Don H. Linszen, Matthew W. State, Richard M. Myers, Soumya Raychaudhuri, Lizzy Rossin, Howard J. Edenberg, Michael E. Goddard, S. Hong Lee, Elisabeth B. Binder, Pablo V. Gejman, William A. Scheftner, Wolfgang Maier, Judith A. Badner, Christel M. Middeldorp, Maria Helena Pinto de Azevedo, Johannes H. Smit, Willem A. Nolen, Lieuwe de Haan, Gonneke Willemsen, Keith Matthews, Ellen M. Wijsman, Jennifer K. Lowe, Rebecca McKinney, Magdalena Gross, Dorothy E. Grice, James A. Knowles, Andrew C. Heath, Jana Strohmaier, Vishwajit L. Nimgaonkar, William Byerley, William E. Bunney, Dan E. Arking, Andrew McQuillin, William M. McMahon, Manuel Mattheisen, Hans-Christoph Steinhausen, Joseph Biederman, Guy A. Rouleau, James J. McGough, Sian Caesar, Edward M. Scolnick, Lefkos T. Middleton, Jack D. Barchas, Ian B. Hickie, Danyu Lin, Patrik K. E. Magnusson, Douglas Blackwood, Francis J. McMahon, Ingrid Agartz, Elena Maestrini, Marian L. Hamshere, Lindsey Kent, Walter J. Muir, Stephan Ripke, Lydia Krabbendam, Christine Fraser, Maria Hipolito, Louise Frisén, Eric Fombonne, Emma M. Quinn, Michael Bauer, Richard P. Ebstein, Michael Steffens, Jordan W. Smoller, Stanley J. Watson, Michael Boehnke, Philip Asherson, Agatino Battaglia, Elliot S. Gershon, Russell Schachar, Marcus Ising, Peng Zhang, Margaret A. Pericak-Vance, Joachim Hallmayer, Sean Ennis, Radhika Kandaswamy, René S. Kahn, Susanne Hoefels, Thomas W. Mühleisen, Pamela Sklar, Paul Lichtenstein, Verneri Anttila, Michael L. Cuccaro, Florian Holsboer, René Breuer, Eric M. Morrow, Vinay Puri, Naomi R. Wray, Szabocls Szelinger, Sabine M. Klauck, John B. Vincent, Shrikant Mane, Aribert Rothenberger, Marion Friedl, Ian Jones, Khalid Choudhury, Michael R. Barnes, Adebayo Anjorin, Edwin H. Cook, William Lawson, Allan H. Young, Lambertus Klei, Bryan J. Mowry, Johannes Schumacher, Michael Gill, James L. Kennedy, Marcella Rietschel, Aiden Corvin, Henrik B. Rasmussen, Susmita Datta, Kimberly Chambert, Daniel Moreno-De-Luca, Benjamin S. Pickard, Stan F. Nelson, Veronica J. Vieland, Stephen W. Scherer, Peter M. Visscher, John Strauss, Andreas Reif, Andrew D. Paterson, Ann Olincy, Phoenix Kwan, Anthony J. Bailey, Patrick F. Sullivan, Pierandrea Muglia, Gunnar Morken, Susanne Lucae, Ayman H. Fanous, Jacob Lawrence, Donald J. MacIntyre, Nancy G. Buccola, Rita M. Cantor, Christina M. Hultman, Weihua Guan, Anthony P. Monaco, Jouke-Jan Hottenga, Elaine Kenny, Jianxin Shi, Dale R. Nyholt, Kevin A. McGhee, Falk W. Lohoff, Jonna Kuntsi, Niklas Långström, John I. Nurnberger, Nelson B. Freimer, Erin N. Smith, John P. Rice, Michael T. Murtha, Thomas H. Wassink, Alexandre A. Todorov, Edmund J.S. Sonuga-Barke, Dan Rujescu, Roy H. Perlis, John S. Witte, Christopher A. Walsh, Matthew C. Keller, Pamela B. Mahon, Patrick J. McGrath, Susan L. Santangelo, Annette M. Hartmann, Ole A. Andreassen, Tatiana Foroud, Shaun Purcell, Josef Frank, Douglas F. Levinson, William Coryell, Ana Miranda, Alan F. Schatzberg, Peter Szatmari, Jun Li, Gerome Breen, Stephen V. Faraone, Anil K. Malhotra, Helena Medeiros, Martin A. Kohli, Nicholas Bass, Catherine Lord, Peter Propping, Wei Xu, Federica Tozzi, Ivan Nikolov, Jan K. Buitelaar, Thomas G. Schulze, Katherine Gordon-Smith, Michele L. Pergadia, Fritz Poustka, Valentina Moskvina, David Curtis, Tobias Banaschewski, Devin Absher, Danielle Posthuma, Stanley Zammit, Gary Donohoe, Ingrid Melle, Karola Rehnström, Thomas Hansen, Myrna M. Weissman, Stanley I. Shyn, Hakon Hakonarson, Christa Lese Martin, Digby Quested, Darina Czamara, Jeremy R. Parr, Pamela A. F. Madden, Jens Treutlein, Aarno Palotie, Robert Freedman, Sandra Meier, Bru Cormand, Nicholas J. Schork, Michele T. Pato, John R. Kelsoe, Vanessa Hus, Frans G. Zitman, Josephine Elia, David St Clair, Roel A. Ophoff, Peter McGuffin, Jonathan Pimm, Jonathan L. Haines, Wiepke Cahn, Matthew Flickinger, Steven P. Hamilton, Michael John Owen, Paul D. Shilling, Jeremy M. Silverman, David Craig, Mark J. Daly, Sarah E. Medland, Robert D. Oades, Marion Leboyer, Alan R. Sanders, Vihra Milanova, Chunyu Liu, Jobst Meyer, Dorret I. Boomsma, Evaristus A. Nwulia, Thomas B. Barrett, Jennifer L. Moran, Donald W. Black, Mònica Bayés, Witte J.G. Hoogendijk, Franziska Degenhardt, Benjamin M. Neale, Daniel L. Koller, Carlos N. Pato, Nicholas John Craddock, Richard Bruggeman, Enda M. Byrne, Edward G. Jones, Eco J. C. de Geus, Stéphane Jamain, Jubao Duan, Anne Farmer, Astrid M. Vicente, Grant W. Montgomery, Thomas Werge, Cathryn M. Lewis, Srdjan Djurovic, Phil Lee, Richard Anney, Elaine K. Green, Wade H. Berrettini, Peter P. Zandi, Susan L. Slager, Stephanie H. Witt, Ian W. Craig, Lisa Jones, Sven Cichon, Bruno Etain, Mark Lathrop, Hilary Coon, Robert C. Thompson, Lena Backlund, A. Jeremy Willsey, Andres Ingason, Christine M. Freitag, Sandra K. Loo, Guiomar Oliveira, Line Olsen, Edwin J. C. G. van den Oord, Geraldine Dawson, Joseph A. Sergeant, David A. Collier, Farooq Amin, Srinivasa Thirumalai, Manfred Uhr, Joseph Piven, Andrew M. McIntosh, Anjali K. Henders, Urban Ösby, Klaus-Peter Lesch, Tiffany A. Greenwood, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Perceptual and Cognitive Neuroscience (PCN), Lee, S Hong, Ripke, Stephan, Neale, Benjamin M, Faraone, Stephen V, Wray, Naomi R, Cross-Disorder Group of the Psychiatric Genomics Consortium, International Inflammatory Bowel Disease Genetics Consortium (IIBDGC), Queensland Brain Institute, University of Queensland [Brisbane], Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], SUNY Upstate Medical University, State University of New York (SUNY), Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), Psychiatric and Neurodevelopmental Genetics Unit, Queensland Centre for Mental Health Research, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council (MRC)-School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff]-Cardiff University-Institute of Medical Genetics [Cardiff], New South Wales Department of Primary Industries (NSW DPI), Faculty of Land and Food Resources, University of Melbourne, HudsonAlpha Institute for Biotechnology [Huntsville, AL], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Diakonhjemmet Hospital, University of Michigan [Ann Arbor], University of Michigan System, Molecular and Behavioral Neuroscience Institute (MBNI), University of Michigan System-University of Michigan System, Emory University [Atlanta, GA], Oslo University Hospital [Oslo], University College of London [London] (UCL), Trinity College Dublin, Johns Hopkins University School of Medicine [Baltimore], MRC Social Genetic Developmental and Psychiatry Centre, Institute of Psychiatry, King's College London, University of Coimbra [Portugal] (UC), Karolinska Institutet [Stockholm], University of Chicago, University of British Columbia (UBC), Department of Child and Adolescent Psychiatry and Psychotherapy [Mannheim], Universität Heidelberg [Heidelberg] = Heidelberg University, Weill Medical College of Cornell University [New York], GlaxoSmithKline, Glaxo Smith Kline, Portland Veterans Administration Medical Center, Windeyer Institute for Medical Sciences, IRCCS Fondazione Stella Maris [Pisa], University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Centro Nacional de Analisis Genomico [Barcelona] (CNAG), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), European Network of Bipolar Research Expert Centres (ENBREC), ENBREC, Department of Psychiatry [Philadelphia], University of Pennsylvania, Physiopathologie des Maladies du Système Nerveux Central, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche Phytopharmacie et Médiateurs Chimiques (UPMC), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Massachusetts General Hospital [Boston, MA, USA], University of Iowa [Iowa City], University of Edinburgh, Royal Hospital for Sick Children [Edinburgh], The Scripps Research Institute [La Jolla, San Diego], MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London-The Institute of Psychiatry, Institute of Medical Sciences, University of Aberdeen, Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London, Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg] = Heidelberg University-Central Institute of Mental Health Mannheim, Department of Psychiatry, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG), Trinity College Dublin-St. James's Hospital, School of Nursing, Louisiana State University (LSU), Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], Department of Psychiatry and Human Behavior, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Friedman Brain Institute, Mount Sinai, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Seaver Autism Center for Research and Treatment, Department of Neuroscience, Departments of Psychiatry, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Seaver Autism Center-, The Mindich Child Health & Development Institute, Friedman Brain Institute, The Mindich Child Health and Development Institute, University of California [San Francisco] (UC San Francisco), Department of Psychiatry, School of Clinical and Experimental Medicine, University of Alabama at Birmingham [ Birmingham] (UAB), Department of Human Genetics, Los Angeles, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Stanley Center for Psychiatric Research, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Mental Health Sciences Unit, Department of Genomics, Life and Brain Center, Universität Bonn = University of Bonn, Institute of Human Genetics, Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Academic Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Department of Disability and Human Development, University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Department of Developmental Neuroscience, Neuropsychiatric Genetics Research Group, University of California [San Diego] (UC San Diego), John P. Hussman Institute for Human Genomics, University of Miami [Coral Gables], East London NHS Foundation Trust, Queen Mary University of London (QMUL), Max-Planck-Institut für Psychiatrie, Genetics Institute, Autism Speaks and the Department of Psychiatry, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), School of Neurology, Neurobiology and Psychiatry, Royal Victoria Infirmary, Medstar Research Institute, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Deparment of Medical Genetics, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Department of Psychiatry and Behavioral Sciences, University of Chicago-NorthShore University Health System, Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine (LSHTM), Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, Psychology Department, National University of Singapore (NUS), Department of Biochemistry and Molecular Biology, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indiana University System-Indiana University System, Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University (VCU), University of Dundee School of Medicine, University of Dundee, Department of Biostatistics and Center for Statistical Genetics, University of Michigan System-University of Michigan System-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Child Psychiatry, McGill University = Université McGill [Montréal, Canada]-Montreal Children's Hospital, McGill University Health Center [Montreal] (MUHC)-McGill University Health Center [Montreal] (MUHC), Howard University College of Medicine, University of Colorado [Denver], Center for Neurobehavioral Genetics, Department of Genomics, Department of Molecular Medicine, Department of Neurology, University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], Medical Research Council-Cardiff University, Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Fisico-Quimica Biologica, Universidade Federal do Rio de Janeiro (UFRJ), Vanderbilt Brain Institute, Vanderbilt University School of Medicine [Nashville], Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania-Children’s Hospital of Philadelphia (CHOP ), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Institute for Human Genetics, Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Department of Clinical and Developmental Psychology, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Clinical Research Unit, Brain & Mind Research Institute-The University of Sydney, Functional Genomics, Neuronal Plasticity / Mouse Behaviour, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Medical Epidemiology and Biostatistics (MEB), Autism and Communicative Disorders Centre, Center for Human Genetic Research, Center for neuroscience-University of California [Davis] (UC Davis), Bioinformatics Research Center, North Carolina State University [Raleigh] (NC State), Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU)-Norwegian University of Science and Technology (NTNU), Emory University [Atlanta, GA]-Atlanta Veterans Affairs Medical Center, Psychiatric Neurogenetics Section, Centre for Addiction and Mental Health, School of Medicine, University of St Andrews [Scotland], Institute of Human Genetics [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Division of Molecular Genome Analysis, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Ecology and Evolutionary Biology, Insitute of Neuroscience and Physiology, University of Gothenburg (GU), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Developmental Brain and Behaviour Unit, University of Southampton, Division of Psychiatric Genomics, Rheinische Friedrich-Wilhelms-Universität Bonn, Statistical Genetics Group, Department of Human Genetics, Department of Pharmacy and Biotechnology, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Department of Psychiatry and Psychotherapy, Department of Mental Health, Johns Hopkins University and Hospital, W.M. Keck Biotechnology Resource Laboratory, Yale University [New Haven], Institutes of Neuroscience and Health and Society, Newcastle University [Newcastle], Genetic Epidemiology Unit, Queensland Institute of Medical Research, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], Sorlandet Hospital HF, Division of Psychiatry, University of Edinburgh-Royal Edinburgh Hospital, Medical Genetics Section, University of Edinburgh-Western General Hospital, Unit on the Genetic Basis of Mood and Anxiety Disorders, National Institutes of Health [Bethesda] (NIH), Unidade de Neurodesenvolvimento e Autismo (UNDA), Hospital Pediatrico de Coimbra, Division of Mental Health and Addiction, Molecular Psychiatry Laboratory, University of Michigan System-University of Michigan System-Molecular and Behavioral Neuroscience Institute, Research and Development, First Psychiatric Clinic-Alexander University Hospital, Registo Oncológico Regional-Sul, Instituto Português de Oncologia de Francisco Gentil, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, St. Olav's Hospital, Brown University, Department of Molecular Biology, Cell Biology and Biochemistry, Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig-Universität Leipzig, Human Genetics Department, University of Pittsburgh (PITT), Institute for Biomedical Imaging and Life Science, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Head of Medical Sequencing, Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, The Centre for Applied Genomics, Toronto, The Hospital for sick children [Toronto] (SickKids)-University of Toronto-Department of Molecular Genetics-McLaughlin Centre, Carolina Institute for Developmental Disabilities, Analytic and Translational Genetics Unit, Rush University Medical Center [Chicago], Julius-Maximilians-Universität Würzburg (JMU), Washington University in Saint Louis (WUSTL), Department of Statistics, Carnegie Mellon University [Pittsburgh] (CMU), Department of Experimental Clinical and Health Psychology, Universiteit Gent = Ghent University (UGENT), Department of Child and Adolescent Psychiatry, Georg-August-University = Georg-August-Universität Göttingen, Department of Medicine, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM)-Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Departments of Psychiatry and Genetics, Yale School of Medicine [New Haven, Connecticut] (YSM), Maine Medical Center, Free University of Amsterdam, Department of Psychiatry and Behavioral Sciences [Stanford], Pathology and Laboratory Medicine, The Scripps Translational Science Institute and The Scripps Research Institute, Psychiatric Center Nordbaden, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), The Scripps Translational Science Institute and Scripps Health, Child and Adolescent Psychiatry, Aarhus University Hospital, Molecular Neuropsychiatry and Development Laboratory, Department of Molecular Physiology & Biophysics and Psychiatry, Vanderbilt University [Nashville]-Centers for Human Genetics Research and Molecular Neuroscience, Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario]-Offord Centre for Child Studies, The Translational Genomics Research Institute (TGen), Oxford Health NHS Foundation Trust, Marlborough House Secure Unit, Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), BioFIG, Center for Biodiversity, Functional and Integrative Genomics, Battelle Center for Mathematical Medicine, Ohio State University [Columbus] (OSU)-Nationwide Children's Hospital, University of Toronto, Diamantina Institute, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Departments of Biostatistics and Medicine, University of Washington [Seattle], ArcelorMittal Maizières Research SA, ArcelorMittal, Institute of Mental Health, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), Psychiatrie & Neuropsychologie, Farmacologie en Toxicologie, RS: CARIM School for Cardiovascular Diseases, RS: MHeNs School for Mental Health and Neuroscience, Biological Psychology, Educational Neuroscience, Clinical Neuropsychology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, LEARN! - Social cognition and learning, Biophotonics and Medical Imaging, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, LEARN! - Brain, learning and development, EMGO+ - Mental Health, LEARN!, Neuroscience Campus Amsterdam - Brain Imaging Technology, LaserLaB - Biophotonics and Microscopy, State University of New York (SUNY)-State University of New York (SUNY), Department of Neuroscience and Physiology, Faculty of Land and Environment, Biosciences Research Division, Department of Environment and Primary Industries Victoria, Department of Epidemiology and Biostatistics, University of California [San Francisco] (UCSF), University of California-University of California, Universität Heidelberg [Heidelberg], Cornell University [New York]-Weill Medical College of Cornell University [New York], Bioinformatics, Internal Medicine, Portland Va Medical Center : Ganzini Linda MD, Technische Universität Dresden = Dresden University of Technology (TU Dresden)-University Hospital Carl Gustav Carus, Centro Nacional de Análisis Genómico (CNAG), Parc Científic de Barcelona (PCB), University of Pennsylvania [Philadelphia], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Division Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, Radboud university [Nijmegen]-Radboud university [Nijmegen], University of California [Irvine] (UCI), University of California-University of California-University of California [Los Angeles] (UCLA), University of Bonn, University of California-University of California-David Geffen School of Medicine [Los Angeles], Cardiff University-Medical Research Council, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Children’s Hospital of Philadelphia (CHOP ), Bureau d'Économie Théorique et Appliquée (BETA), Institut National de la Recherche Agronomique (INRA)-Université de Strasbourg (UNISTRA)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University of Oxford [Oxford], Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], University of Toronto-The Hospital for sick children [Toronto] (SickKids)-Department of Molecular Genetics-McLaughlin Centre, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Universiteit Gent = Ghent University [Belgium] (UGENT), University of Göttingen - Georg-August-Universität Göttingen, Yale University School of Medicine, Georg-August-University [Göttingen], ANS - Amsterdam Neuroscience, Adult Psychiatry, Child Psychiatry, Psychiatry, Human genetics, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, Perlis RH, Mowry BJ, Thapar A, Goddard ME, Witte JS, Absher D, Agartz I, Akil H, Amin F, Andreassen OA, Anjorin A, Anney R, Anttila V, Arking DE, Asherson P, Azevedo MH, Backlund L, Badner JA, Bailey AJ, Banaschewski T, Barchas JD, Barnes MR, Barrett TB, Bass N, Battaglia A, Bauer M, Bayés M, Bellivier F, Bergen SE, Berrettini W, Betancur C, Bettecken T, Biederman J, Binder EB, Black DW, Blackwood DH, Bloss CS, Boehnke M, Boomsma DI, Breen G, Breuer R, Bruggeman R, Cormican P, Buccola NG, Buitelaar JK, Bunney WE, Buxbaum JD, Byerley WF, Byrne EM, Caesar S, Cahn W, Cantor RM, Casas M, Chakravarti A, Chambert K, Choudhury K, Cichon S, Cloninger CR, Collier DA, Cook EH, Coon H, Cormand B, Corvin A, Coryell WH, Craig DW, Craig IW, Crosbie J, Cuccaro ML, Curtis D, Czamara D, Datta S, Dawson G, Day R, De Geus EJ, Degenhardt F, Djurovic S, Donohoe GJ, Doyle AE, Duan J, Dudbridge F, Duketis E, Ebstein RP, Edenberg HJ, Elia J, Ennis S, Etain B, Fanous A, Farmer AE, Ferrier IN, Flickinger M, Fombonne E, Foroud T, Frank J, Franke B, Fraser C, Freedman R, Freimer NB, Freitag CM, Friedl M, Frisén L, Gallagher L, Gejman PV, Georgieva L, Gershon ES, Geschwind DH, Giegling I, Gill M, Gordon SD, Gordon-Smith K, Green EK, Greenwood TA, Grice DE, Gross M, Grozeva D, Guan W, Gurling H, De Haan L, Haines JL, Hakonarson H, Hallmayer J, Hamilton SP, Hamshere ML, Hansen TF, Hartmann AM, Hautzinger M, Heath AC, Henders AK, Herms S, Hickie IB, Hipolito M, Hoefels S, Holmans PA, Holsboer F, Hoogendijk WJ, Hottenga JJ, Hultman CM, Hus V, Ingason A, Ising M, Jamain S, Jones EG, Jones I, Jones L, Tzeng JY, Kähler AK, Kahn RS, Kandaswamy R, Keller MC, Kennedy JL, Kenny E, Kent L, Kim Y, Kirov GK, Klauck SM, Klei L, Knowles JA, Kohli MA, Koller DL, Konte B, Korszun A, Krabbendam L, Krasucki R, Kuntsi J, Kwan P, Landén M, Långström N, Lathrop M, Lawrence J, Lawson WB, Leboyer M, Ledbetter DH, Lee PH, Lencz T, Lesch KP, Levinson DF, Lewis CM, Li J, Lichtenstein P, Lieberman JA, Lin DY, Linszen DH, Liu C, Lohoff FW, Loo SK, Lord C, Lowe JK, Lucae S, MacIntyre DJ, Madden PA, Maestrini E, Magnusson PK, Mahon PB, Maier W, Malhotra AK, Mane SM, Martin CL, Martin NG, Mattheisen M, Matthews K, Mattingsdal M, McCarroll SA, McGhee KA, McGough JJ, McGrath PJ, McGuffin P, McInnis MG, McIntosh A, McKinney R, McLean AW, McMahon FJ, McMahon WM, McQuillin A, Medeiros H, Medland SE, Meier S, Melle I, Meng F, Meyer J, Middeldorp CM, Middleton L, Milanova V, Miranda A, Monaco AP, Montgomery GW, Moran JL, Moreno-De-Luca D, Morken G, Morris DW, Morrow EM, Moskvina V, Muglia P, Mühleisen TW, Muir WJ, Müller-Myhsok B, Murtha M, Myers RM, Myin-Germeys I, Neale MC, Nelson SF, Nievergelt CM, Nikolov I, Nimgaonkar V, Nolen WA, Nöthen MM, Nurnberger JI, Nwulia EA, Nyholt DR, O'Dushlaine C, Oades RD, Olincy A, Oliveira G, Olsen L, Ophoff RA, Osby U, Owen MJ, Palotie A, Parr JR, Paterson AD, Pato CN, Pato MT, Penninx BW, Pergadia ML, Pericak-Vance MA, Pickard BS, Pimm J, Piven J, Posthuma D, Potash JB, Poustka F, Propping P, Puri V, Quested DJ, Quinn EM, Ramos-Quiroga JA, Rasmussen HB, Raychaudhuri S, Rehnström K, Reif A, Ribasés M, Rice JP, Rietschel M, Roeder K, Roeyers H, Rossin L, Rothenberger A, Rouleau G, Ruderfer D, Rujescu D, Sanders AR, Sanders SJ, Santangelo SL, Sergeant JA, Schachar R, Schalling M, Schatzberg AF, Scheftner WA, Schellenberg GD, Scherer SW, Schork NJ, Schulze TG, Schumacher J, Schwarz M, Scolnick E, Scott LJ, Shi J, Shilling PD, Shyn SI, Silverman JM, Slager SL, Smalley SL, Smit JH, Smith EN, Sonuga-Barke EJ, St Clair D, State M, Steffens M, Steinhausen HC, Strauss JS, Strohmaier J, Stroup TS, Sutcliffe JS, Szatmari P, Szelinger S, Thirumalai S, Thompson RC, Todorov AA, Tozzi F, Treutlein J, Uhr M, van den Oord EJ, Van Grootheest G, Van Os J, Vicente AM, Vieland VJ, Vincent JB, Visscher PM, Walsh CA, Wassink TH, Watson SJ, Weissman MM, Werge T, Wienker TF, Wijsman EM, Willemsen G, Williams N, Willsey AJ, Witt SH, Xu W, Young AH, Yu TW, Zammit S, Zandi PP, Zhang P, Zitman FG, Zöllner S, Devlin B, Kelsoe JR, Sklar P, Daly MJ, O'Donovan MC, Craddock N, Sullivan PF, Smoller JW, Kendler KS, Wray NR, Cardiff University-Medical Research Council (MRC), HudsonAlpha Institute for Biotechnology, The Institute of Psychiatry-King‘s College London, Cornell University-Weill Medical College of Cornell University [New York], Stanford University Medical School, Technische Universität Dresden (TUD)-University Hospital Carl Gustav Carus, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, McGill University-Montreal Children's Hospital, Universidade Federal do Rio de Janeiro [Rio de Janeiro] (UFRJ), Stanford University School of Medicine [Stanford], Stanford University [Stanford], Eberhard Karls Universität Tübingen, Friedrich Alexander University [Erlangen-Nürnberg], Università di Bologna [Bologna] (UNIBO), University of Toronto-The Hospital for Sick Children-Department of Molecular Genetics-McLaughlin Centre, Washington University School of Medicine, Ghent University [Belgium] (UGENT), University of Goettingen, CHUM Research Center, Psychiatry and Behavioral Science, Stanford University School of Medicine [CA, USA], Aalborg Psychiatric Hospital, Aarhus University Hospital, Washington University in St Louis, Instituto Nacional de Saude Dr Ricardo Jorge, Oades, Robert D., Guellaen, Georges, Medical Oncology, Epidemiology, Child and Adolescent Psychiatry / Psychology, and Hematology

Subjects
Netherlands Twin Register (NTR), Medizin, Inheritance Patterns, Social Sciences, AUTISM SPECTRUM DISORDERS, nosology, heritability, COMMON SNPS, 0302 clinical medicine, Crohn Disease, SCHIZOPHRENIA, Child, Psychiatric genetics, Genetics & Heredity, MAJOR DEPRESSIVE DISORDER, RISK, 0303 health sciences, ATTENTION-DEFICIT/HYPERACTIVITY DISORDER, 120 000 Neuronal Coherence, Mental Disorders, Variants, BIPOLAR DISORDER, ASSOCIATION, Genomic disorders and inherited multi-system disorders [DCN PAC - Perception action and control IGMD 3], Psychiatric Disorders, CROHNS-DISEASE, 3. Good health, Schizophrenia, genetic association study, Medical genetics, Major depressive disorder, SNPs, Adult, medicine.medical_specialty, genetic etiology, medical genetics, DEFICIT HYPERACTIVITY DISORDER, Biology, Polymorphism, Single Nucleotide, behavioral disciplines and activities, Article, Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3], Heritability, Genetic Heterogeneity, 03 medical and health sciences, Prevalence of mental disorders, mental disorders, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, medicine, ddc:61, Humans, Attention deficit hyperactivity disorder, Genetic Predisposition to Disease, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, DCN PAC - Perception action and control NCEBP 9 - Mental health, ddc:610, Medizinische Fakultät » Universitätsklinikum Essen » LVR-Klinikum Essen » Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters, Bipolar disorder, Psychiatry, 030304 developmental biology, Depressive Disorder, Major, Genome, Human, Genetic heterogeneity, medicine.disease, schizophrenia, Attention Deficit Disorder with Hyperactivity, Child Development Disorders, Pervasive, Perturbações do Desenvolvimento Infantil e Saúde Mental, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

AM Vicente - Cross-Disorder Group of the Psychiatric Genomics Consortium Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

Published
2013

48. Autism, affective disorders, and social phobia

Author

James T. McCracken, Peter E. Tanguay, and Susan L. Smalley

Subjects
Male, Proband, Intelligence, Intellectual Disability, mental disorders, medicine, Humans, Family, Autistic Disorder, First-degree relatives, Child, Genetics (clinical), Depression (differential diagnoses), Models, Genetic, Mood Disorders, business.industry, medicine.disease, Phobic Disorders, Mood disorders, Seizure Disorders, Case-Control Studies, Child, Preschool, Autism, Major depressive disorder, Anxiety, Female, medicine.symptom, business, Clinical psychology
Abstract

The purpose of this study is to test the hypothesis that major affective and/or anxiety disorders are increased among relatives of autistic probands compared with controls. Among 36 families with an autistic child, 23 (64%) have a first degree relative diagnosed with major depressive disorder and 14 (39%) have a first degree relative diagnosed with social phobia. These rates are significantly greater than the 19% and 5%, respectively, found among 21 families with a child having a genetic condition, tuberous sclerosis complex, or a seizure disorder but no autism. The frequency of major depression among the 96 first degree relatives of autistic probands is 37.5% compared with 11.1% found among 45 relatives of control probands. The frequency of social phobia, 20.2%, is approximately 10 times more common than that found among the relatives of the control probands (2.4%). Elevated rates of both major depression and social phobia are found among parents and siblings in the families with an autistic child. Furthermore, 64% of parents affected with a major depression had the onset of the first depressive episode prior to the birth of the autistic child and all parents with social phobia had the onset of condition prior to the birth of the autistic child. Family patterns differ depending on the intellectual level of the autistic child; specifically, social phobia is significantly greater among the first degree relatives of nonretarded autistic probands than among relatives of individuals with autism and comorbid mental retardation. Whether this familial association of autism, major mood disorders, and social phobia reflects shared genetic underpinnings requires further research. © 1995 Wiley-Liss, Inc.

Published
1995

49. Phenotypic variation of tuberous sclerosis in a single extended kindred

Author

Susan L. Smalley, F Burger, and Moyra Smith

Subjects
Adult, Male, congenital, hereditary, and neonatal diseases and abnormalities, Adolescent, Neuropsychological Tests, Biology, Interviews as Topic, Tuberous sclerosis, Tuberous Sclerosis, Locus heterogeneity, hemic and lymphatic diseases, Genetic variation, Genetics, medicine, Humans, Physical Examination, neoplasms, Gene, Genetics (clinical), Mental Disorders, Chromosome Mapping, Genetic Variation, Chromosome, medicine.disease, Phenotype, nervous system diseases, Variation (linguistics), embryonic structures, Female, Lod Score, TSC2, Chromosomes, Human, Pair 16, Research Article
Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with a great degree of phenotypic variability. Given the presence of two gene loci underlying this disorder, locus heterogeneity may account for some of the variability. However, significant within family variation suggests that different genes do not explain the majority of this variation. The purpose of this research is to identify physical and behavioural variation in expression of TSC in a single large extended kindred. TSC in this kindred is cosegregating with markers localised to chromosome 16p13.3. The expression of TSC in this kindred is quite variable with a substantial proportion of persons showing very mild physical expression of TSC. In contrast to very mild physical expression of TSC in some family members, there is a significant clustering of psychiatric disorders among persons affected with TSC compared to their unaffected relatives. This finding, coupled with the mild physical expression of TSC in some family members, supports a hypothesis that the TSC2 gene may present phenotypically as mild skin signs and significant behavioural problems.

Published
1994

50. Commingling analysis of memory performance in elderly men

Author

Susan L. Smalley, Asenath La Rue, Bonnie H. Wolkenstein, Christina G.S. Palmer, and Gary E. Swan

Subjects
education.field_of_study, Epidemiology, Offspring, Population, Cognition, Biology, medicine.disease, Disease cluster, Major gene, Benton Visual Retention Test, medicine, Dementia, Memory disorder, education, Genetics (clinical), Demography
Abstract

Smalley et al. [(1992) Genet Epidemiol 9:333–345] found evidence of a mixture of two distributions in memory performance among offspring of patients with dementia of the Alzheimer type (DAT), suggesting that these groups reflect genotypic subgroups of carriers and non-carriers of a putative DAT gene. One prediction of this hypothesis is that, in the general population, two distributions of memory performance are present, with a smaller proportion of subjects in the low-scoring cluster than that found among the offspring sample, but similar to the prevalence of DAT in the elderly community-at-large. Memory performance was investigated in a large sample of normal elderly males (N = 1,149; mean age = 71.4 ± 4.7 years) to test this hypothesis. Commingling analyses of performance on the Benton visual retention test demonstrated significant negative skewness in the distribution of memory performance, requiring a transformation to fit a single normal distribution. In the absence of a transformation, two distributions fit better than one, with 6% of subjects falling into a “low”-scoring cluster. These findings are consistent with the hypothesis that memory performance may represent a premorbid or morbid difference in those who go on to develop, or currently have, DAT, possibly allowing identification of at-risk carriers of a putative single major gene for DAT. © 1994 Wiley-Liss, Inc.

Published
1994

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