Severe Self-Injury in Persons with Autism and Related Neurodevelopmental Disorders: Differences in Sensory, Autonomic, and Immune Markers Suggest Hyperalgesia

Background:   Self-injurious behavior (SIB) is a costly and treatment resistant form of repetitive behavior seen in the context of neurodevelopmental disorders such as autism. Physiological mechanisms regulating SIB have been understudied. Conventional wisdom surrounding self-injurious behavior is that persons who engage in SIB are insensitive to pain; however, studies directly examining sensory function and relevant biomarkers are needed. 

Objectives:  We provide a survey of a series of studies that we have conducted designed to test this pain insensitivity hypothesis of SIB.

Methods:  81 consecutively recruited cases with a clinical diagnosis of ASD were evaluated using research diagnostic criteria for ASD (ADOS, ADIR, & expert clinical opinion), and were then subgrouped based on nonverbal IQ (> 90; < 70) resulting in samples of n = 30 cases with ASD + cognitive impairment (ASD+ID), n = 41 cases with ASD and no cognitive impairment (ASD-only), and 10 excluded cases.  Cases were evaluated for the presence and severity of SIB using a mulitmethod phenotypic battery that included a set of SIB measures (RBSR, Clinical Interview for Repetitive Behaviors, YBOCS, observational coding of repetitive behaviors). In a sample of 34 cases with severe SIB (occurred at least daily, persisted at least 12 months, was the focus of active intervention) and 17 non-SIB cases matched on age and IQ, measures from quantitative sensory testing (heat, cold, pin prick, deep pressure), saliva samples (cortisol, alpha amylase), and 3mm epidermal punch biopsies taken from non-SIB sites (ENF density/morphology, neuropeptide content, mast cell degranulation) were analyzed.

Results:   SIB occurred in ASD+ID (63%) and ASD-only (24%) subgroups, but severity was significantly greater in the ASD+ID subgroup (p = .002), and only occurred frequently during sampled direct observations in the ASD+ID subgroup.  Analysis of a separate severe SIB subsample compared to matched ID controls indicated: (1) that cases with chronic SIB were characterized by increased behavioral markers of sensory reactivity during quantitative sensory testing (facial action coding of pain signs - sham trials < sensation trials [p < .05] SIB > non SIB [p < .03], (2) that sensory reactivity (magnitude of facial action units in response to sensation trials) was correlated with ENF innervation [r = 0.47, P < .001], (3) that substance P (SP) positive fiber counts tended to be greater in SIB cases, and (4) that peripheral innervation of epidermal nerve fibers in SIB cases was marked by differences in nerve morphology (density, distribution) and increased evidence of altered immune system activity in the form of degranulated mast cells [p < .01]. 

Conclusions:   Taken together, our work suggests that at least a subgroup of individuals with chronic repetitive SIB may be in a physiological state similar to neuropathic pain / hyperalgesia associated with alterations in inflammatory, immune, and nociceptive systems. If so, this may provide a set of accessible, objective biomarkers of altered sensory function that may help identify the need for treatment and perhaps also mark the course of treatment response in this vulnerable but under-researched subgroup.