Executive function in young preschool children with symptoms of ADHD Annette Holth Skogan Child and Adolescent Mental Health Research Unit Oslo University Hospital, Ullevål Submitted for the PhD degree at the Department of Psychology, Faculty of Social Sciences, University of Oslo, 2015 © Annette Holth Skogan, 2015 Series of dissertations submitted to the Faculty of Social Sciences, University of Oslo No. 514 ISSN 1504-3991 All rights reserved. No part of this publication may be reproduced or transmitted, in any form or by any means, without permission. Cover: Hanne Baadsgaard Utigard. Printed in Norway: AIT Oslo AS. Produced in co-operation with Akademika publishing, Oslo. The thesis is produced by Akademika publishing merely in connection with the thesis defence. Kindly direct all inquiries regarding the thesis to the copyright holder or the unit which grants the doctorate. TABLE OF CONTENTS AKNOWLEDGEMENTS ........................................................................................................... I SUMMARY ............................................................................................................................. III ABBREVIATIONS ................................................................................................................... V LIST OF PAPERS ................................................................................................................ VI 1. INTRODUCTION .............................................................................................................. 1 1.1. Perspectives and definitions ........................................................................................ 2 1.1.1. ADHD .................................................................................................................. 2 1.1.2. ADHD in preschool age ....................................................................................... 3 1.1.3. Executive function ................................................................................................ 5 1.1.3.1. Inhibition ....................................................................................................... 6 1.1.3.2. Working memory .......................................................................................... 6 1.1.3.3. Mental flexibility .......................................................................................... 7 1.1.3.4. Planning ........................................................................................................ 7 1.1.3.5. Emotional control .......................................................................................... 8 1.1.4. Structural organization of early EF ...................................................................... 9 1.2. Neurocognition in ADHD ......................................................................................... 10 1.2.1. Neuropsychological endophenotypes for ADHD .............................................. 11 1.2.2. Executive dysfunction in preschool children with ADHD ................................. 12 1.2.2.1. Evidence from clinically administered tests ............................................... 12 1.2.2.2. Evidence from behavior ratings .................................................................. 13 1.2.3. EF in preschool children with symptoms of ADHD: A summary ..................... 14 2. OBJECTIVES .................................................................................................................. 15 3. MATERIALS AND METHODS ..................................................................................... 16 3.1. Sample ....................................................................................................................... 16 3.2. Participants ................................................................................................................ 18 3.2.1. Paper I ................................................................................................................ 18 3.2.2. Paper II ............................................................................................................... 19 3.2.3. Paper III .............................................................................................................. 19 3.3. Measures .................................................................................................................... 19 3.3.1. Preschool Age Psychiatric Assessment (PAPA) interview ................................ 20 3.3.2. General intellectual ability ................................................................................. 20 3.3.3. Working memory ............................................................................................... 20 3.3.4. Inhibition ............................................................................................................ 21 3.3.5. BRIEF-P ............................................................................................................. 22 3.4. Statistical analyses ..................................................................................................... 22 3.5. Ethics ......................................................................................................................... 24 4. MAIN FINDINGS ............................................................................................................ 25 4.1. Paper I ........................................................................................................................ 25 4.2. Paper II ...................................................................................................................... 25 4.3. Paper III ..................................................................................................................... 26 5. GENERAL DISCUSSION ............................................................................................... 27 5.1. Methodological considerations .................................................................................. 27 5.1.1. The measurement of executive function in preschool children .......................... 27 5.1.1.1. Neuropsychological assessment .................................................................. 28 5.1.1.2. Behavior ratings .......................................................................................... 31 5.1.1.3. Relationships between neuropsychological tests and BRIEF-P ratings ..... 34 5.1.2. Representativeness and generalizability of findings .......................................... 40 5.1.3. Strengths and limitations, a summary ................................................................ 42 5.2. Interpretation of the main results ............................................................................... 42 5.2.1. Differentiation and structural organization of early EF ..................................... 43 5.2.2. EF in young preschool children with symptoms of ADHD ............................... 46 5.2.3. Neuropsychological tests and behavioral ratings as measures of emerging EF . 50 5.3. Implications ............................................................................................................... 52 5.3.1. Implications for clinical practice ........................................................................ 52 5.3.2. Implications for future research ......................................................................... 53 References ................................................................................................................................ 55 Appendix .................................................................................................................................. 76 Papers I-III AKNOWLEDGEMENTS The research presented in this thesis was conducted between 2010 and 2015 at the Division of Mental Health and Addiction at Oslo University Hospital, based on data from two large studies, the Mother and Child Cohort study (MoBa) at the Norwegian Institute of Public Health and the ADHD study, a collaboration between the Norwegian Institute of Public Health and Oslo University Hospital. I would like to thank: All the children and their parents for their efforts taking part in the ADHD study. My supervisor, Professor at the University of Oslo, Jens Egeland for solid guidance and encouragement. His fascinating ability to combine enthusiasm and creativity with clear thinking and profound knowledge has inspired and guided me during the writing of this thesis. Heidi Aase, PhD and my co-supervisor, for her continuous support, generosity, sharp thinking and friendly guidance. Anne-Grethe Urnes, clinical neuropsychologist, for sharing her vast knowledge of child neuropsychology and for introducing me to this field of research many years ago. Pål Zeiner, PhD, for enduring support and guidance, and for not letting me forget the clinical perspective- asking ”so what”? Ted Reichborn-Kjennerud, Professor at the University of Oslo, for valuable, critical article review. Pål Zeiner, and Anne Margrethe Myhre, Associate Professor at the University of Oslo and Head of Division of Mental Health and Addiction at Oslo University Hospital for providing a supportive base, and the University of Oslo for the doctoral education programme. All the dedicated people in the ADHD-study, Eli Nyhus and Line Glemmestad in particular, for the years spent obtaining valuable data for the ADHD study. It was a fantastic workplace! Friends and colleagues Kristin Romvig Øvergaard and Nina Rohrer-Baumgartner, for their friendship and support during these years of work. In their company, getting stuck (in an elevator or in a manuscript) is not necessarily a problem. Beate Ørbeck, PhD, for her clear thinking, enthusiasm and support when the going gets tough. I My parents Annelise and Knut, for always being there, with all sorts of support, and for teaching me to persist. My parents in-law, Sigrid and Knut, for their generous and valuable help all along. My three-year old niece Ylva for generously sharing inside information. Finally, the love of my life, Tor, and our sons Sindre and Erlend. I could not have completed this project without your patience, love and care. Thank you. The presented research received financial support from: -The South Eastern Health Region, -Oslo University Hospital and -The Norwegian Resource Centre for ADHD, Tourette´s syndrome, and Narcolepsy. II SUMMARY The overarching goal of research presented in this thesis was to provide new knowledge about basic, self-regulatory skills- or executive function (EF)- in young preschool children with behavioral symptoms characteristic of Attention-Deficit/Hyperactivity Disorder (ADHD). Etiological models of ADHD emphasize an onset during kindergarten and preschool years, and neuropsychological theories have converged on deficits in early developing EF processes as a possible developmental pathway towards ADHD. Despite a growing interest in EF development and the introduction of several developmentally appropriate methods of EF measurement for use with the youngest age groups, studies addressing EF in young children with elevated levels of ADHD symptoms are still scarce. Research hypotheses in this thesis had thus to be based on theoretical models of EF development, together with findings from the preschool group as a whole (pooled data from children aged 3 –6 years), and from older children. We hypothesized that EF structure in early preschool years would differ from that described in older children (Paper II), but that associations between deficiencies in early emerging EF processes and symptoms of ADHD would be identifiable. This was expected to hold both when EF was assessed through neuropsychological tests (Paper I), and by use of parents’ ratings of EF behavior in everyday settings (Paper III). The relationship between clinically administered tests of EF and parents’ ratings of EF behavior was specifically addressed in an additional empirical chapter. Our results indicate that at age three, some differentiation has taken place, which is measurable both by neuropsychological tasks and ratings of EF behavior in everyday settings. Labels used to define EF subcomponents in school-aged children and adolescents may not map directly onto emerging EF skills during early preschool years. Performance on neuropsychological tests of inhibition and working memory were related to symptoms of ADHD in our sample. Effect sizes were small, limiting the measures’ clinical utility at this early stage in development. Behavioral ratings of EF in these two domains were more closely related to symptoms of ADHD than the performance-based measures. According to parent ratings of EF, children meeting diagnostic criteria for ADHD presented with higher problem scores across EF domains, and a different EF profile relative to children with internalizing problems and typically developing controls. We found that performance-based measures of EF and ratings of EF behavior were related in our sample. These two methods of III measurement are likely to tap into different aspects of early EF and should not be used interchangeably as parallel measures of EF. IV ABBREVIATIONS ANOVA Analysis of Variance ANCOVA Analysis of Covariance BRIEF-P Behavior Rating Inventory of Executive Function - Preschool Version CFA Confirmatory Factor Analysis DSM Diagnostic and Statistical Manual for Mental Disorders EF Executive function EdF Executive dysfunction EFA Exploratory Factor Analysis MANOVA Multiple Analysis of Variance MANCOVA Multiple Analysis of Covariance ODD Oppositional Defiant Disorder PAPA Preschool Age Psychiatric Assessment interview PFC Prefrontal Cortex PCA Principal Components Analysis SPSS Statistical Package for Social Sciences StB Stanford-Binet Intelligence Scales VWM Verbal Working Memory NVWM Nonverbal Working Memory V LIST OF PAPERS I Skogan, A.H., Zeiner, P., Egeland, J., Rohrer-Baumgartner, N., Urnes, A-G., Reichborn-Kjennerud, T., Aase, H. (2014). Inhibition and working memory in young preschool children with symptoms of ADHD and/or oppositional- defiant disorder. Child Neuropsychology, 20, 607-624. II Skogan, A.H., Egeland, J., Zeiner, P., Overgaard, K.R., Oerbeck, B., Reichborn- Kjennerud, T., Aase, H. (2014). Factor structure of the Behavior Rating Inventory of Executive Functions (BRIEF-P) at age three years. Child Neuropsychology, advance online publication, doi: 10.1080/09297049.2014.992401. III Skogan, A.H., Zeiner, P., Egeland, J., Urnes, A-G., Reichborn-Kjennerud, T., Aase, H. (2015). Parent ratings of executive function in young preschool children with symptoms of attention deficit hyperactivity disorder. Behavioral and Brain Functions, 11:16. doi: 10.1186/s12993-015-0060-1. VI