title: Subtyping attention-deficit/hyperactivity disorder using temperament dimensions: toward biologically based nosologic criteria.
abstract: Psychiatric nosology is limited by behavioral and biological heterogeneity within existing disorder categories. The imprecise nature of current nosologic distinctions limits both mechanistic understanding and clinical prediction. We demonstrate an approach consistent with the National Institute of Mental Health Research Domain Criteria initiative to identify superior, neurobiologically valid subgroups with better predictive capacity than existing psychiatric categories for childhood attention-deficit/hyperactivity disorder (ADHD).
  
  
  
  To refine subtyping of childhood ADHD by using biologically based behavioral dimensions (i.e., temperament), novel classification algorithms, and multiple external validators.
  
  
  
  A total of 437 clinically well-characterized, community-recruited children, with and without ADHD, participated in an ongoing longitudinal study. Baseline data were used to classify children into subgroups based on temperament dimensions and examine external validators including physiological and magnetic resonance imaging measures. One-year longitudinal follow-up data are reported for a subgroup of the ADHD sample to address stability and clinical prediction.
  
  
  
  Parent/guardian ratings of children on a measure of temperament were used as input features in novel community detection analyses to identify subgroups within the sample. Groups were validated using 3 widely accepted external validators: peripheral physiological characteristics (cardiac measures of respiratory sinus arrhythmia and pre-ejection period), central nervous system functioning (via resting-state functional connectivity magnetic resonance imaging), and clinical outcomes (at 1-year longitudinal follow-up).
  
  
  
  The community detection algorithm suggested 3 novel types of ADHD, labeled as mild (normative emotion regulation), surgent (extreme levels of positive approach-motivation), and irritable (extreme levels of negative emotionality, anger, and poor soothability). Types were independent of existing clinical demarcations including DSM-5 presentations or symptom severity. These types showed stability over time and were distinguished by unique patterns of cardiac physiological response, resting-state functional brain connectivity, and clinical outcomes 1 year later.
  
  
  
  Results suggest that a biologically informed temperament-based typology, developed with a discovery-based community detection algorithm, provides a superior description of heterogeneity in the ADHD population than does any current clinical nosologic criteria. This demonstration sets the stage for more aggressive attempts at a tractable, biologically based nosology.
authors.affiliation: Division of Psychology, Department of Psychiatry, Oregon Health and Science University, Portland.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Karalunas
authors.affiliation: Division of Psychology, Department of Psychiatry, Oregon Health and Science University, Portland2Department of Behavioral Neuroscience, Oregon Health and Science University, Portland3Advanced Imaging Research Center, Oregon Health and Science University.
authors.forename: Damien
authors.initials: D
authors.lastname: Fair
authors.affiliation: Division of Clinical Science, Department of Psychology, Florida International University, Miami.
authors.forename: Erica D
authors.initials: ED
authors.lastname: Musser
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health and Science University, Portland.
authors.forename: Kamari
authors.initials: K
authors.lastname: Aykes
authors.affiliation: Functional Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Swathi P
authors.initials: SP
authors.lastname: Iyer
authors.affiliation: Division of Psychology, Department of Psychiatry, Oregon Health and Science University, Portland2Department of Behavioral Neuroscience, Oregon Health and Science University, Portland.
authors.forename: Joel T
authors.initials: JT
authors.lastname: Nigg
mesh_terms: D000465:Algorithms; D001289:Attention Deficit Disorder with Hyperactivity / Q000145:classification* / Q000175:diagnosis / Q000503:physiopathology / Q000523:psychology; D001921:Brain / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D004562:Electrocardiography; D005260:Female; D059907:Functional Neuroimaging; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D065809:Respiratory Sinus Arrhythmia / Q000502:physiology; D011795:Surveys and Questionnaires; D013694:Temperament