The role of proopiomelanocortin (POMC) in sequentially dependent self‐injurious behavior

Abstract

Self-injuring behavior (SIB) is a life-threatening behavior exhibited by many species, including humans, and has no known cause and no agreed upon treatment. The role of the stress axis in the maintenance of this mysterious behavior was examined in subjects with life-long SIB. Over a sixyear period, forty hours of direct observations of behavior and the environment were recorded on palmtop computers while 36 residential subjects (28 target and 8 control subjects) conducted their daily activities. Blood samples were collected in morning and evening for all subjects and within minutes after a self-injuring act in 28 target subjects who exhibited SIB to determine levels of ACTH and B-endorphin (BE). Self-injuring events in the patient group were significantly sequentially dependent (i.e. the only predictor of a self-injuring act was an antecedent self-injuring act). Higher morning levels of BE relative to ACTH predicted [r df=27 =0.57, p<.001] the sequentially dependent pattern of SIB. This effect was validated in a subgroup re-tested several months later [r df=22 =0.60, p<.001]. A subgroup of seven subjects exhibiting sequentially dependent patterns were administered an opiate blocker (naltrexone) in a double-blind, crossover design with an additional 14 hours/week of observation for seven weeks. Naltrexone challenge interrupted the sequential pattern (improved behavior) in subjects with elevated BE immediately following SIB (r=0.85, p<0.01). The pattern of results supported the conclusion that the stress axis played a significant role in the maintenance of complex episodes of self-injury.

Naltrexone treatment reverses astrocyte atrophy and immune dysfunction in self-harming macaques

“…Later case reports have noted efficacy of naltrexone treatment for impulse control disorders and self-injury, particularly in populations with developmental delay (Modesto-Lowe and Van Kirk, 2002), or in juveniles (Willemsen-Swinkels et al, 1995). Additional research suggests that elevated beta-endorphin levels following self-injury may predict response to treatment for SIB (Sandman et al, 2008). Furthermore, nonhuman primates with SIB also have reduced levels of plasma beta-endorphin immunoreactivity (Tiefenbacher et al, 2005; Tiefenbacher et al, 2004), similar to findings of reduced opioid activity in individuals with autism (Willemsen-Swinkels et al, 1996).…”

Multidisciplinary Assessment and Treatment of Self-Injurious Behavior in Autism Spectrum Disorder and Intellectual Disability: Integration of Psychological and Biological Theory and Approach

“…The degree of association between these products normally increases with stress, exertion, or pain (Holson et al 1988;Oltras et al 1987). In more detailed research, the probability that an opioid blocker would be an effective treatment for a patient with SIB was thought to be predictable by the amount of dysregulation of the plasma POMC products (elevated BE compared to ACTH) in the morning and the measurement of BE immediately after SIB (Kemp et al 2008;Sandman et al 1990Sandman et al , 1997Sandman et al , 2008. It has been proposed that patients with recurrent temporal patterns of SIB may represent a subtype of patients whose behaviors are maintained by BE and ACTH (Kemp et al 2008).…”

Self-injurious behavior in neurodevelopmental disorders: Relevance of nociceptive and immune mechanisms

“…Thus, an additional feature of SIB correlated with at least three structural characteristics (frequency, intensity, and location) is that SIB activates inflammatory mechanisms (an inherent biological property associated with injury) (Moalem & Tracey, 2006) which, in turn, leads to an immune response; another biological reality (Dantzer et al 2008). One plausible outcome, particularly if the SIB is poorly managed is a potentially potent and deleterious feed-forward cycle in which more SIB (see Sandman’s contagion model [Sandman et al 2008]), leads to more tissue damage, leading to additional release of inflammatory and immune mediators. Inflammation and immune activation, in turn, lead to the release of mediators that produce pain.…”