Jennifer L. Barron

Naloxone attenuates self-abusive behavior in developmentally disabled clients

The opiate antagonist naloxone was effective in reducing self-abusive behavior in two mentally retarded clients with an extensive history of such behavior. Three doses of naloxone (0.1, 0.2, 0.4 mg) were compared with a vehicle solution in a double-blind, crossover design. Naloxone greatly attenuated self-abusive episodes in one client and eliminated them entirely in the second client. In addition, use of self-restraining behavior by one client was reduced. The findings suggested that some clients with self-injurious behavior may have disturbances of the endogenous opiate system. Maintenance of self-abuse by tonically elevated pain threshold and/or by the putative addictive characteristics of such behavior was discussed.

Memory deficits associated with chronic fatigue immune dysfunction syndrome.

Performance on tests of memory in 39 patients who met Center for Disease Control (CDC) criteria for chronic fatigue immune dysfunction syndrome (CFIDS) was compared with 23 depressed patients (DSM-III-R) and 129 healthy controls. Although the CFIDS patients had normal neuropsychological profiles, they significantly overestimated their ability (metamemory), performed significantly worse on tests of recall as context increased (e.g., recognition), made more errors when rehearsal was prevented, and had delayed mental scanning as memory load increased. The overall pattern indicated that CFIDS patients had a significant memory deficit, far worse than implied by CDC criteria. The pattern for CFIDS patients was consistent with temporal-limbic dysfunction and significantly different than depressed patients and control subjects.

Naltrexone reduces self-injury and improves learning.

Author(s): Sandman, CA; Hetrick, WP; Taylor, DV; Barron, JL; Touchette, P; Lott, I; Crinella, F; Martinazzi, V | Abstract: A cross-over study of 24 Ss with self-injurious behavior (SIB) was conducted over a continuous 10-week period. Treatment with naltrexone (NTX) was provided for 3 weeks in a randomized, reversal design with different doses or placebo each week. Videotaped observations (20 hr/subject), neurological examinations, and ratings of adaptive and maladaptive behavior were collected. Treatment with 2 mg/kg NTX produced at least a 50% reduction in SIB in a significant (p l.01) number of Ss. The 1.0 mg/kg was less effective (p l.02), and no significant change was observed at 0.5 mg/kg. Eighteen of 21 Ss achieved at least a 25% reduction in SIB after treatment of at least 1 dose of NTX (p l.0001). More than half of the Ss (52%) had a l 50% reduction (p l.001), and a significant number of Ss (33%) decreased SIB by more than 75% after at least 1 dose of NTX. Significant improvement was measured after NTX on measures of learning and attention.

Long-Term Effects of Naltrexone on Self-Injurious Behavior.

A subgroup of self-injuring patients responds positively to the opiate-blocking agent naltrexone in acute, double-blind studies. In this study we examined the effects of naltrexone after acute treatment and the long-term effects of naltrexone on SIB. Rates of SIB were collected from pretreatment baseline; a second baseline a year after the acute trial; and a subsequent 12-month double-blind, placebo-controlled treatment. A subgroup of patients decreased SIB for a year without treatment after acute exposure to naltrexone. Five participants who decreased SIB by 70% after acute treatment increased SIB to the long-term treatment with naltrexone. In contrast, those for whom SIB increased over the one-year treatment hiatus decreased their SIB after the first long-term treatment. Discussion of these complex effects considered the role of background opioid levels, dosing, and treatment regimen of naltrexone and other factors limiting receptor adaptation among patients who exhibit SIB.

Effect of naltrexone upon self-injurious behavior, learning and activity: a case study

Naltrexone significantly attenuated self-injurious behavior in a 20-year-old mildly retarded autistic male patient. The patient was videotaped daily and behavior was evaluated with a time-sampling procedure. Behavioral ratings of SIB frequency, SIB severity, and activity were collected automatically with a computerized system. Learning and memory were tested on a weekly basis with a modification of a paired associate learning test (PALT). Treatment with naltrexone resulted in (a) attenuation of SIB in the unstructured setting and (b) improvements in learning and memory without influencing activity levels.

Self-injurious behavior and stereotypy in an institutionalized mentally retarded population

Demographic variables and behavioral characteristics of institutionalized mentally retarded clients exhibiting both self-injurious behavior (SIB) and stereotypy, stereotypy alone, SIB alone, or neither of these behaviors were analyzed. Overall, there were no significant differences for the demographic variables measured. Multivariate analyses revealed that severity and frequency of behavior, sensory handicap, and sex of the subject were the best predictors of group membership. Moreover, this research suggests that SIB and stereotypy can be classified as stereotyped SIB and withdrawal stereotypy, respectively. Thus, the treatment modalities presently being applied to these behaviors could be inappropriate. Additional evidence is discussed that supports the belief that an organic physiological substrate or mechanism could be related to these aberrant behavior patterns, which would necessitate a new diagnostic classification and alternative forms of treatment.

Disregulation of hypothalamic-pituitary-adrenal axis in the mentally retarded

Previous reports of cognitive and social improvement in the mentally retarded after administration of MSH/ACTH fragments suggested disregulation of the hypothalamic-pituitary-adrenal (HPA) axis. The current study examined the integrity of this system with the Dexamethasone Suppression Test (DST). The DST is a biological index of HPA integrity and recently has been used as a diagnostic aid for endogenous depression. Thirty-five mentally retarded patients were administered 1 mg of dexamethasone just after a sample of blood was taken. Blood samples were analyzed for cortisol by RIA at 11:00 p.m. (basal), 8:00 a.m., 4:00 p.m., and 10:00 p.m. Between 40% and 48% (depending on sampling) of the patients failed to suppress cortisol (greater than 4 micrograms/dl), after the DST challenge. The results suggested that a significant proportion of mentally retarded patients have a DST index reflecting a disordered HPA axis and complements earlier studies of cognitive enhancement observed after treatment with MSH/ACTH fragments. The possibility that the stress of hospitalization was related to a disordered HPA was suggested. The possible co-existence of depression in the mentally retarded invites further study.

Naltrexone improves learning and attention in self-injurious individuals with developmental disabilities

In the primary study, 10 patients were enrolled in a 10-week double-blind evaluation of the effectiveness of naltrexone in reducing self-injurious behavior (SIB) in adults with developmental disabilities. Within this study, the effects of naltrexone on acquisition of a paired associates task were investigated. The effects of three doses of naltrexone (0.5, 1.0, and 2.0 mg/kg orally) were tested on separate weeks. Learning evaluations were conducted on Wednesday of each week. Naltrexone improved measures of independence and attention, and decreased trial rate.

Parameters of the event-related potential are related to functioning in the mentally retarded

Event-related potentials were measured in 39 institutionalized profoundly and severely retarded clients divided into two groups: clients assigned to sheltered workshop (WS); and clients, residentially matched, but not assigned to workshop (NSW). Since the groups differed in intelligence (p less than 0.01) the ERP was evaluated by analysis of covariance with IQ as the covariate. The WS group had significantly shorter latency of components reflecting initial registration (P1) and channeling (N1) of sensory input and significantly greater amplitude of indices of enhanced perception (P2) and cognitive elaboration (N2). The WS group had significantly more complex waves than the NWS group. A modest (r=0.31, p less than 0.05) relationship between P2 and IQ was observed. Multiple correlations of composite measures of the ERP with IQ were not significant but higher in the NWS than WS group. The possibilities that the ERP be used as a supplemental metric for functional evaluation or that the workshop experience might stimulate central nervous system plasticity were discussed.

Paradoxical response to sedative/hypnotics in patients with Self-injurious behavior and stereotypy

Paradoxical response to sedative medication has been reported previously among patients with Self-injurious (SIB) and Stereotypic (ST) Behavior (Barron and Sandman, 1983, 1985). The prevalence of this marker was examined in 648 consecutive developmentally delayed patients tested in the EEG laboratory. Several analyses compared response to sedative/hypnotics, assessment of the EEG, and behavioral profiles from the most recent annual comprehensive behavioral/medical evaluation (CDER). The presence of SIB and ST were significantly related to paradoxical response. The EEG was not related to paradoxical response, but had fewer epileptic foci in frequent or severe SIB and/or ST.