One opiate hypothesis suggests that self-injurious behavior (SIB) is related to elevated sensory thresholds. The present study examined the relationship between scores on the Motivation Assessment Scale (MAS) (Durand and Crimmins, 1988), a 16-item scale designed to determine variables that maintain SIB in developmentally delayed individuals, and response to naltrexone (an opiate blocker). High baseline levels of SIB in 20 subjects were significantly correlated with observations that SIB was maintained by need for attention as measured by the MAS. There were no significant correlations between scores on the MAS and change in SIB to the most effective dose of naltrexone (2.0 mg/kg). The present findings did not support the relationship between response to naltrexone and sensory scores on the MAS. © 1995 Plenum Publishing Corporation.

Proopiomelanocortin (POMC) contains several interesting, behaviorally active peptides. Release patterns of these fragments have been related to bizarre episodes of self-injurious behavior (SIB) among autistic individuals. Moreover, elevation in beta-endorphin (betaE) but not ACTH levels was associated with a positive response to an acutely administered, centrally acting opioid blocker among autistic individuals exhibiting SIB. In the present study, POMC fragments were measured in 12 self-injurious patients before and after long term (3 month) treatment with an opiate blocker naltrexone (NTX). POMC fragments were sampled from blood collected at the beginning of the baseline and placebo-controlled treatment phases of the study. Results indicated that the co-release (coupling) of POMC fragments were stable over time and the profile of POMC fragments in plasma predicted the effectiveness of a CNS acting drug in autistic subjects who self-injure.

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. © 1993 Plenum Publishing Corporation.

Central nervous system (CNS) inhibitory mechanisms hypothesized to "gate" repetitive sensory inputs have been implicated in the pathology of schizophrenia. The present study investigated gender differences in inhibitory gating of evoked brain responses to repeated stimuli in normal subjects (30 women and 30 men) using an auditory conditioning-testing paradigm. Pairs of click stimuli (S1 and S2) were presented with a 0.5 s intrapair and a 10 s interpair interval. The amplitudes and latencies of the P50, N100, P180 components of the auditory evoked response to the conditioning (S1) and test response (S2) were measured, and the gating ratios were computed (T/C ratio = S2/S1 * 100). The amplitudes to S1 were not significantly different between men and women at P50, N100, or P180. However, women had significantly higher amplitudes to S2 at P50 (p = 0.03) and N100 (p = 0.04). The T/C ratios for women were higher (i.e., less suppression of response to S2) for P50 (p = 0.08) and N100 (p = 0.04) compared to men. The results suggested that differences in auditory gating between men and women were not due to biological differences in the P50 and N100 generators but possibly to differential influence of inhibitory mechanisms acting on the generator substrates of these evoked responses.

The conditioning-testing (S1-S2) P50 auditory evoked potential (EP) has been well-documented and accepted as an important tool for measuring sensory gating in schizophrenia research. However, the physiological mechanism of the phenomenon is not known. In this study a single-trial analysis was used to determine the influence of the latency variability of the responses in the formation of the averaged P50. Ten schizophrenic patients and 10 normal controls were tested in the dual-click EP paradigm. Using ensemble averaging analysis, we replicated the previous finding of a lower S1 P50 amplitude and higher S2/S1 ratio in schizophrenics compared with normal controls. The single-trial analysis revealed that patients had significantly higher trial-to-trial latency variability in S1 responses than normal subjects, while the S2 showed the same variability as in controls. Measured by the single-trial procedure, the arithmetic mean amplitudes of P50 responses to S1 and S2 were similar between normal and schizophrenic subjects. The same measure also eliminated the difference in averaged P50 amplitude between S1 and S2 for both groups. Temporal variability appears to be an important factor in the assessment of averaged EPs and thus contribute to the change of P50 amplitude observed in schizophrenia.

Neurodevelopmental benefits of increased gestation have not been fully characterized in terms of network organization. Since brain function can be understood as an integrated network of neural information from distributed brain regions, investigation of the effects of gestational length on network properties is a critical goal of human developmental neuroscience. Using diffusion tensor imaging and fiber tractography, we investigated the effects of gestational length on the small-world attributes and rich club organization of 147 preadolescent children, whose gestational length ranged from 29 to 42 weeks. Higher network efficiency was positively associated with longer gestation. The longer gestation was correlated with increased local efficiency in the posterior medial cortex, including the precuneus, cuneus, and superior parietal regions. Rich club organization was also observed indicating the existence of highly interconnected structural hubs formed in preadolescent children. Connectivity among rich club members and from rich club regions was positively associated with the length of gestation, indicating the higher level of topological benefits of structural connectivity from longer gestation in the predominant regions of brain networks. The findings provide evidence that longer gestation is associated with improved topological organization of the preadolescent brain, characterized by the increased communication capacity of the brain network and enhanced directional strength of brain connectivity with central hub regions.

Socioeconomic disadvantage is associated with atypical development in specific brain regions, yet the relation between poverty and whole brain network organization (i.e., the connectome, a set of brain regions connected with neuronal pathways) has not been characterized. Developmental studies indicate that the connectome undergoes rapid change during childhood and is consequently likely to be highly sensitive to both salutary and detrimental influences. We investigated associations between the socioeconomic disparities measured by the income-to-needs ratio (INR) in childhood and structural brain network organization with 144 healthy children between 6 and 11 years of age (mean age = 8 years). INR of girls was positively and logarithmically associated with the extent to which brain networks were efficiently organized, suggesting that girls in more impoverished environments had less efficient brain network organization. Lower INR was associated with network inefficiency in multiple cortical regions including prefrontal cortex, cingulate, and insula, and in subcortical regions including the hippocampus and amygdala. These findings suggest that childhood poverty may result in wide-spread disruptions of the brain connectome among girls, particularly at the lowest INR levels, and are differentially expressed in females and males.

Many studies have found that the P50 sensory gating ratio in a paired click task is smaller in normal control subjects than in patients with schizophrenia, indicating more effective sensory gating. However, a wide range of gating ratios has been reported in the literature for both groups. The purpose of this study was to compile these findings and to compare reported P50 gating ratios in controls and patients with schizophrenia. Current data collected from individual controls in eight studies from the University of California, Irvine (UCI), Indiana University (IU), and Yale University also are reported. The IU, UCI, and Yale data showed that approximately 40% of controls had P50 ratios within 1 S.D. below the mean of means for patients with schizophrenia. The meta-analysis rejected the null hypothesis that all studies showed no effect. The meta-analysis also showed that the differences were not the same across all studies. The mean ratios in 45 of the 46 group comparisons were smaller for controls than for patients, and the observed difference in means was significant for 35 of those studies. Reported gating ratios for controls from two laboratories whose findings were reported in the literature differed from all the other control groups. Variables affecting the gating ratio included band pass filter setting, rules regarding the inclusion of P30, sex, and age. Standards of P50 collection and measurement would help determine whether the gating ratio can be sufficiently reliable to be labeled an endophenotype, and suggestions are made toward this goal.

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 <.01) number of Ss. The 1.0 mg/kg was less effective (p <.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 <.0001). More than half of the Ss (52%) had a < 50% reduction (p <.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.