An Individualized, Data-Driven Biological Approach to Attention-Deficit/Hyperactivity Disorder (ADHD) Heterogeneity

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed mental health disorder in childhood, however, there is well-established heterogeneity in both the presentation of ADHD symptoms and secondary characteristics across the literature. Existing Diagnostic and Statistical Manual of Mental Disorders (DSM-5) nosology has been ineffective in explaining such heterogeneity in terms of both pathophysiology and clinical trajectories. The current study investigated ADHD heterogeneity via a biologically-based, data-driven approach (k-Means algorithm). Specifically, unique biological profiles (derived from patterns of parasympathetic and sympathetic functioning) were identified and utilized as predictors of clinical presentations. Two hundred eighty-nine participants (167 youth with ADHD), ages 5 to 13 years, completed an emotion-based task while indexes of parasympathetic (i.e., respiratory sinus arrhythmia [RSA]) and sympathetic (i.e., electrodermal activity [EDA]) activity were obtained. Overall, results suggest that three distinct biological profiles among youth with ADHD are evident, with biological profiles differing in regulation and arousal levels during emotionally evocative contexts: (Profile 1) underregulated, hyperaroused (negative contexts only), (Profile 2) typically regulated, underaroused, and (Profile 3) overregulated (positive contexts only), hyperaroused. Results are supported by several dopaminergic- and reward-based theories, integrating differing concepts across the literature, and adds biological support for existing models. Behaviorally, results may translate into differing clinical presentations, however, further work is needed. In general, youth with ADHD are heterogenous in autonomic functioning, which could have implications for synthesizing across differing theories within the literature, predicting clinical presentations, and developing targeted treatments.

Keywords: Attention-deficit/hyperactivity disorder (ADHD); Clinical heterogeneity; Electrodermal activity (EDA); Respiratory sinus arrhythmia (RSA).