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 6-year period, 40 hr 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) = .57, p < .001] the sequentially dependent pattern of SIB. This effect was validated in a subgroup retested several months later [r(df=22) = .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 hr/week of observation for 7 weeks. Naltrexone challenge interrupted the sequential pattern (improved behavior) in subjects with elevated BE immediately following SIB (r = .85, p < .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.

FIGURE 1

Presents the mean z-score distributions for the relations between SIB and both antecedent (before) and subsequent (following) behavioral events. For instance, the probability that an SIB even either preceded or followed another SIB event was highly significant (the dotted lines depict the p<.01 level of significance). Staff interaction was significantly less probable both before and after an SIB event. [SIB (self injurious behavior), Staff Prox (Proximity of Staff to subject), Restraint (presence or absence of restraining devices), Peer (presence or absence of peer interactions), Agitation (hyperactivity, temper tantrums), Stereo (Stereotypy-repetitive body movements), Null (30 second periods without recordable events)].

FIGURE 2

Panel A illustrates that increases in morning E (higher log values) are associated significantly higher transitional probabilities for SIB (greater degree of contagion). Panel B presents the same data for a subgroup of 23 of the same subjects tested nine to twelve months after the initial evaluation (presented in Panel A). Panel C is a subgroup of subjects from Panel A who were selected by staff at the beginning of the study as exhibiting the most severe SIB.

FIGURE 3

An increase in E within five minutes of an observed self-injury predicts a positive response (decreased SIB contagion) to subsequent treatment with Naltrexone.