Subtyping Attention-Deficit/Hyperactivity Disorder Using Temperament Dimensions

Abstract

IMPORTANCE 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).OBJECTIVE To refine subtyping of childhood ADHD by using biologically based behavioral dimensions (ie, temperament), novel classification algorithms, and multiple external validators. DESIGN, SETTING, AND PARTICIPANTSA 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. MAIN OUTCOMES AND MEASURESParent/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). RESULTSThe community detection algorithm suggested 3 novel types of ADHD, labeled as mild (normative emotion regulation), surgent (extreme levels of positive approachmotivation), 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. CONCLUSIONS AND RELEVANCEResults 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.

Cognitive Subtypes of Schizophrenia Characterized by Differential Brain Volumetric Reductions and Cognitive Decline

“…Thus, the deteriorated group, as originally pre- sis of the IQ classification analysis results presented here, which are supported by the volumetric differences. Overall, our findings confirm that schizophrenia may be classified on the basis of distinct subgroups related to IQ deterioration from premorbid levels, which may account for the neurobiological heterogeneity present in the illness, as shown in other disorders 22 in which temperament-based attention-deficit/hyperactivity disorder subgroups were related to resting-state functional connectivity MRI. Lending further support to the existence of a distinct, severely deteriorated subset of patients with schizophrenia is our finding that this group had the largest and most widespread reductions based on cognitive, functional, emotional, and brain volumetric measures relative to healthy controls, which is generally consistent with the findings of previous studies.…”

Impulsivity and Aggression in Female BPD and ADHD Patients: Association with ACC Glutamate and GABA Concentrations

“…Comorbidities were somewhat less frequent in the ADHD group. Nevertheless, ADHD, as recently described by Karalunas et al, 2014, is not a uniform disorder but can further be divided into three subtypes by a biologically informed temperament-based typology, thus impulsivity and aggression might not be equally expressed in these three subtypes, which we did not differentiate. Furthermore, our MRS findings are not yet linked to other imaging parameters such as default mode network connectivity or task-related functional activation.…”

Types of adult attention-deficit hyperactivity disorder (ADHD): baseline characteristics, initial response, and long-term response to treatment with methylphenidate

“…Rösler et al (2008), using a different scoring technique for the German version of the WRAADDS, reported a two-factor result in which the emotional items loaded on the same factor as hyperactivity. Finally, Karalunas et al (2014) published a report using a cluster analysis methodology and scores from a temperament scale to arrive at three types of ADHD children. One had prominent anger as a distinguishing feature, while a second evidenced high levels of positive approach motivation.…”