Autonomic Regulation as a Therapeutic Target in Attention-Deficit/Hyperactivity Disorder: A Narrative Review and Novel Phenotype-Guided Intervention Protocol

This document presents the study protocol for a Phase IIa proof-of-concept investigation of the Autonomic Regulation Protocol (ARP), a manualized psychotherapy intervention for adults with attention-deficit/hyperactivity disorder (ADHD). The ARP targets autonomic nervous system dysregulation — a well-documented but therapeutically unaddressed neurobiological substrate of ADHD — through three integrated components: (1) baseline autonomic phenotyping to classify patients into hypo-aroused, hyper-aroused, or mixed autonomic profiles using heart rate variability (HRV) metrics, (2) individualized resonance frequency HRV biofeedback as a standalone mechanistic intervention, and (3) phenotype-matched somatic regulation tools prescribed according to the patient's autonomic profile. The study employs a multiple-baseline across-clients single-case experimental design (SCED) with 5–8 adult participants, following the ORBIT (Obesity-Related Behavioral Intervention Trials) model for behavioral treatment development. The primary outcome is change in resting RMSSD (root mean square of successive differences), a validated index of vagally-mediated HRV and autonomic flexibility. Secondary outcomes include the Difficulties in Emotion Regulation Scale (DERS), the Adult ADHD Self-Report Scale (ASRS-v1.1), the Behavior Rating Inventory of Executive Function–Adult Version (BRIEF-A), and the Sheehan Disability Scale (SDS). Prespecified Go/No-Go criteria for advancement to a pilot randomized controlled trial are included. This protocol is publicly archived prior to data collection to establish transparency, intellectual priority, and methodological accountability. No existing manualized intervention integrates autonomic phenotyping, standalone HRV resonance frequency biofeedback, and somatic regulation matching for ADHD within a single protocol. The research program aligns with the NIMH Research Domain Criteria (RDoC) framework and the R61/R33 experimental therapeutics mandate. Author: Marisa Cherry, LCSW Contact: [email protected]