Using Mobile Technology to Reduce Engagement in Stereotypy: A Validation of Decision-Making Algorithms.

We developed an iOS app, the iSTIM, designed to support parents of children with autism spectrum disorders (ASD) in reducing common repetitive vocal and motor behavior (i.e., stereotypy). The purpose of our study was to preliminarily test the decision-making algorithms of the iSTIM using trained university students to implement the assessments and interventions. Specifically, we examined the effects of the iSTIM on stereotypy and functional engagement in 11 children with ASD within alternating treatment designs. Using the iSTIM reduced engagement in stereotypy for eight participants and increased functional engagement for four of those participants. Our results indicate that the iSTIM may decrease engagement in stereotypy but that some of the decision-making algorithms may benefit from modifications prior to testing with parents.

Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children.

OBJECTIVES: Autism spectrum disorder (ASD) is a developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and non-verbal communication, and stereotyped patterns of interests and activities. Vitamin-D deficiency was previously reported in autistic children. However, the data on the relationship between vitamin D deficiency and the severity of autism are limited. METHODS: We performed a case-controlled cross-sectional analysis conducted on 122 ASD children, to assess their vitamin D status compared to controls and the relationship between vitamin D deficiency and the severity of autism. We also conducted an open trial of vitamin D supplementation in ASD children. RESULTS: Fifty-seven percent of the patients in the present study had vitamin D deficiency, and 30% had vitamin D insufficiency. The mean 25-OHD levels in patients with severe autism were significantly lower than those in patients with mild/moderate autism. Serum 25-OHD levels had significant negative correlations with Childhood Autism Rating Scale (CARS) scores. Of the ASD group, 106 patients with low-serum 25-OHD levels (<30 ng/ml) participated in the open label trial. They received vitamin D3 (300 IU/kg/day not to exceed 5000 IU/day) for 3 months. Eighty-three subjects completed 3 months of daily vitamin D treatment. Collectively, 80.72% (67/83) of subjects who received vitamin D3 treatment had significantly improved outcome, which was mainly in the sections of the CARS and aberrant behavior checklist subscales that measure behavior, stereotypy, eye contact, and attention span. CONCLUSION: Vitamin D is inexpensive, readily available and safe. It may have beneficial effects in ASD subjects, especially when the final serum level is more than 40 ng/ml. TRIAL REGISTRATION NUMBER: UMIN-CTR Study Design: trial Number: R000016846.

A trial of D-cycloserine to treat stereotypies in older adolescents and young adults with autism spectrum disorder.

OBJECTIVES: Autism spectrum disorders (ASDs) have core impairments in social communication as well as the presence of repetitive, stereotypic behaviors and restricted interests. Older adolescents and young adults are particularly impacted by these deficits. Preclinical data implicate glutamatergic dysfunction in the pathophysiology of ASDs. D-Cycloserine (DCS), a partial glycineB agonist at the N-methyl-D-aspartic acid receptor site, has been shown to improve sociability in mouse models and a small human study. The sensitivity of the obligatory glycineB co-agonist binding site may change with daily administration of DCS as a result of agonist-induced desensitization. The efficacy of a "pulsed" once-weekly administration versus "daily" administration of DCS was compared. METHODS: Males and females, ages 14 to 25 years, with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision diagnosis of an ASD were enrolled in a double-blind, randomized 10-week trial consisting of 8 weeks of active drug with either weekly or daily administration of 50 mg of DCS followed by a 2-week follow-up visit. RESULTS: For the purposes of this study, no statistical or clinical differences existed between the 2 dosage groups on the Aberrant Behavior Checklist subscale 3, which measures stereotypies/repetitive movements. When combining groups, a statistically significant decrease of 37% was found from baseline to week 8 when study drug was completed using a linear mixed effects model (P = 0.003). CONCLUSIONS: D-Cycloserine was shown to be effective in improving stereotypic symptoms in older adolescents and young adults with ASDs measured by the Aberrant Behavior Checklist subscale 3. In addition, DCS was safe and well tolerated.

Pre-treatment of BALB/c mice with a centrally acting serotonin antagonist (cyproheptadine) reduces mortality from Boophone disticha poisoning.

INTRODUCTION: Crude extracts of Boophone disticha are used in Southern African traditional medical practice for the management of various illnesses and conditions and have also been abused for their claimed euphoric and hallucinogenic effects. Unfortunately, ingestion of Boophone disticha has resulted in toxicity and death. The results of a recent acute toxicity study in a rat model insinuated that central nervous system (CNS) serotonin overdrive could be the cause of toxicity in B. disticha poisoning. The present work sought to test that hypothesis by investigating whether pre-treatment of B. disticha poisoned BALB/c mice with the CNS acting serotonin antagonist, cyproheptadine, has a dose-dependent protective effect on toxicity and mortality. METHODS: A hydroethanolic extract of B. disticha was used in all the experiments. Five groups each with 10 animals were constituted as follows; a negative control group (received 10 ml/kg Normal Saline), a positive control group (received 375 mg/kg of the B. disticha extract), and three test groups each receiving 10 mg/kg, 15 mg/kg and 20 mg/kg cyproheptadine intraperitoneally 15 minutes before oral gavage administration of 375 mg/kg B. disticha extract respectively. The Functional Observational Battery was used to evaluate neurobehavioral and physiological changes resulting from toxicity of the plant extract. The mice were then placed in an open field for another five minutes and the number of rearings and border crossings were counted and recorded. Gait abnormalities, involuntary motor movements, mobility, arousal and stereotypical behavior were also scored according to predefined criteria. All open field investigations were recorded electronically using a LABTEC Webcam(®) and results were later analysed and recorded by one of the group members. All results were entered on data collection forms. Time to death (survival time) was considered as the time period from dosage with Boophone disticha to time of death. The study follow up period was 7 days and those mice that were alive at the end of the 7 day follow-up period were considered as having survived the poisoning episode. The Kaplan Meier plot and Log-rank test were used to compare differences in mortality and median time to death for mice in the 5 treatment groups. RESULTS: We found that cyproheptadine pre-treatment led to a dose-dependent decrease in mortality from 80% in the group not pre-treated with cyproheptadine, to 30% in the 15 and 20 mg/kg cyproheptadine pre-treated groups (n = 10 per group, p < 0.05). There was also a dose-dependent increase in median survival times amongst the groups (p < 0.0001). Pre-treatment with cyproheptadine also resulted in a decrease of other toxic symptoms associated with Boophone disticha. CONCLUSIONS: We conclude that cyproheptadine has a dose-dependent protective effect on mortality and toxicity produced by exposure to Boophone disticha in our mouse model of toxicity.

Language use and stereotyping: the role of approach and avoidance motivation goals

The use of more abstract language to describe expected behaviors as opposed to unexpected behaviors has traditionally been considered a way of stereotype maintenance. This tendency is known as linguistic expectancy bias. Two experiments examined the influence of approach and avoidance motivational orientations on the production of this linguistic expectancy bias. It was predicted that approach strategic orientation is likely to describe expectancy consistent behaviors at a higher level of linguistic abstraction than expectancy inconsistent behaviors. In contrast, avoidance strategic orientation is likely to describe both expectancy consistent behaviors and expectancy inconsistent behaviors at a lower level of linguistic abstraction, thus facilitating the disappearance of linguistic expectancy bias. Two experiments confirmed these expectations, using strategic orientation manipulations based either on communication goals or on motor action, and measuring linguistic abstraction either on forced-choice answer format or on free descriptions. Implications for the generalisation of linguistic expectancy bias are discussed (AU)

El uso de un lenguaje más abstracto para describir los comportamientos congruentes con las expectativas que los comportamientos incongruentes con las expectativas es una forma de mantener los estereotipos. Esta tendencia se conoce como el sesgo lingüístico de expectativa. Dos experimentos analizan la influencia de las orientaciones motivacionales de aproximación y evitación en la producción del sesgo lingüístico de expectativa. Se predijo que la orientación estratégica de aproximación promovería que comportamientos consistentes con la expectativa se describiesen con un mayor nivel de abstracción lingüística que los comportamientos inconsistentes con la expectativa. En cambio, la orientación estratégica de evitación induciría a que tanto los comportamientos consistentes como los inconsistentes con las expectativas se describiesen a un menor nivel de abstracción, facilitando con ello la desaparición del sesgo lingüístico de expectativa. Los dos experimentos que se presentan confirmaron dichas predicciones utilizando manipulaciones de orientación estratégica de aproximación y evitación formuladas en forma de metas comunicativas y en forma de acción motora. Además, se midió la abstracción lingüística tanto en formato de respuesta de elección múltiple como en descripción libre. El artículo debate las implicaciones de los estudios para la generalización del sesgo lingüístico de expectativa (AU)

Sensory features and repetitive behaviors in children with autism and developmental delays.

This study combined parent and observational measures to examine the association between aberrant sensory features and restricted, repetitive behaviors in children with autism (N=67) and those with developmental delays (N=42). Confirmatory factor analysis was used to empirically validate three sensory constructs of interest: hyperresponsiveness, hyporesponsiveness, and sensory seeking. Examining the association between the three derived sensory factor scores and scores on the Repetitive Behavior Scales--Revised revealed the co-occurrence of these behaviors in both clinical groups. Specifically, high levels of hyperresponsive behaviors predicted high levels of repetitive behaviors, and the relationship between these variables remained the same controlling for mental age. We primarily found non-significant associations between hyporesponsiveness or sensory seeking and repetitive behaviors, with the exception that sensory seeking was associated with ritualistic/sameness behaviors. These findings suggest that shared neurobiological mechanisms may underlie hyperresponsive sensory symptoms and repetitive behaviors and have implications for diagnostic classification as well as intervention.

Methamphetamine-induced stereotypy correlates negatively with patch-enhanced prodynorphin and arc mRNA expression in the rat caudate putamen: the role of mu opioid receptor activation.

Amphetamines induce stereotypy, which correlates with patch-enhanced c-Fos expression the patch compartment of caudate putamen (CPu). Methamphetamine (METH) treatment also induces patch-enhanced expression of prodynorphin (PD), arc and zif/268 in the CPu. Whether patch-enhanced activation of any of these genes correlates with METH-induced stereotypy is unknown, and the factors that contribute to this pattern of expression are poorly understood. Activation of mu opioid receptors, which are expressed by the neurons of the patch compartment, may underlie METH-induced patch-enhanced gene expression and stereotypy. The current study examined whether striatal mu opioid receptor blockade altered METH-induced stereotypy and patch-enhanced gene expression, and if there was a correlation between the two responses. Animals were intrastriatally infused with the mu antagonist CTAP (10 microg/microl), treated with METH (7.5 mg/kg, s.c.), placed in activity chambers for 3h, and then sacrificed. CTAP pretreatment attenuated METH-induced increases in PD, arc and zif/268 mRNA expression and significantly reduced METH-induced stereotypy. Patch-enhanced PD and arc mRNA expression in the dorsolateral CPu correlated negatively with METH-induced stereotypy. These data indicate that mu opioid receptor activation contributes to METH-induced gene expression in the CPu and stereotypy, and that patch-enhanced PD and arc expression may be a homeostatic response to METH treatment.

An overview of behavioral strategies for reducing hand-related stereotypies of persons with severe to profound intellectual and multiple disabilities: 1995-2007.

This paper provides an overview of behavioral strategies used for reducing hand-related stereotypies (i.e., hand/finger mouthing, eye poking, self-slapping, and other hand-to-head/body responses) of persons with severe to profound intellectual and multiple disabilities. Computerized and manual searches were conducted to identify the studies carried out in this area between 1995 and 2007. Forty-one studies were identified which used five main strategies: (1) mechanical restraints employed alone or together with other intervention variables, (2) response blocking alone or together with other intervention variables, (3) noncontingent stimulation (environmental enrichment) with or without prompting or contingent reinforcement events, (4) contingency manipulations differing from those relied upon by the other strategies, and (5) programs based on microswitch clusters. The outcomes of the studies tended to be positive but occasional failures also occurred. Outcomes were discussed in terms of the characteristics of the strategies employed, the implications of the strategies for the participants' overall stimulation and occupational situation, and the overall practicality, applicability, affordability and potential of the strategies in the short and long term. Issues for future research were also examined.

Reducing student stereotypy by improving teachers' implementation of discrete-trial teaching.

Discrete-trial teaching is an instructional method commonly used to teach social and academic skills to children with an autism spectrum disorder. The purpose of the current study was to evaluate the indirect effects of discrete-trial teaching on 3 students' stereotypy. Instructions, feedback, modeling, and rehearsal were used to improve 3 teaching aides' implementation of discrete-trial teaching in a private school for children with autism. Improvements in accurate teaching were accompanied by systematic decreases in students' levels of stereotypy.

On the role of preference in response competition.

A duration-based preference assessment identified items that matched and did not match the sensory consequences hypothesized to maintain stereotypy. When evaluated in treatment, these items effectively competed with the occurrence of stereotypy, regardless of their sensory properties. It is suggested that relative preference, as measured in duration-based assessment, can be as significant as type of stimulation produced in interventions that reduce automatically reinforced problem behavior.

Standard criteria for relapse are needed in obsessive-compulsive disorder.

To assess how different criteria for relapse affect inferences about relapse in obsessive-compulsive disorder (OCD), a post hoc analysis of relapse was conducted using data from a multisite randomized controlled trial comparing clomipramine (CMI), exposure and ritual prevention (EX/RP), and its combination (EX/RP+CMI) in adults with OCD. Different relapse definitions were constructed based on criteria used in prior studies. For each definition, the number of relapsers was computed, and the proportion of relapsers and time to relapse were compared. When applied to this data set, relapse criteria used in prior OCD studies yielded different observed relapse rates (range: 27-63% for CMI; 0-50% for EX/RP; and 7-67% for EX/RP+CMI). Most criteria found that EX/RP responders (with or without CMI) had a significantly lower relapse rate and longer time to relapse after treatment discontinuation than did responders to CMI alone. However, some relapse criteria (e.g., those requiring minimal worsening) found no significant treatment differences in relapse rates or time to relapse, and some generated biases against one treatment or another. Most definitions concurred: in adults with primary OCD, EX/RP treatment (with or without CMI) can produce more durable short-term gains after treatment discontinuation than CMI alone. However, different relapse criteria can lead to very different observed relapse rates and even contradictory inferences about relapse. Standard criteria for relapse are needed in OCD to facilitate comparisons between studies (enabling better treatment guidelines) and to advance research on mechanisms of relapse and relapse prevention.

Identifying specific sensory modalities maintaining the stereotypy of students with multiple profound disabilities.

In Experiment 1, analogue functional analyses were conducted to identify the functions of stereotypy for six students with multiple profound disabilities. Results indicated that stereotypy (a) occurred across conditions, (b) occurred primarily when alone, or (c) occurred during all sessions except in the Control condition. Experiment 2 analyzed stereotypy while masking visual, auditory, or tactile sensory consequences. Results showed that stereotypy was maintained by visual stimulation, tactile stimulation, or was undifferentiated across conditions. In Experiment 3, we showed that stereotypy could be reduced by providing competing sensory stimulation. In Experiment 4, stereotypy that was undifferentiated in Experiment 1 was analyzed using a concurrent operants procedure. Results showed that stereotypy was not multiply determined, but occurred to produce visual sensory stimulation. Our findings are discussed in terms of the sensory and social reinforcers that maintain stereotypy, assessment procedures used to identify those reinforcers, and the interpretation of assessment results.

Exposure and ritual prevention for obsessive-compulsive disorder: effects of intensive versus twice-weekly sessions.

Exposure and ritual prevention (ERP) is the most effective treatment for obsessive-compulsive disorder (OCD), yet the intensive treatment schedule often described is not transportable to many settings. In the present study, the authors examined whether a twice-weekly (TW) ERP program reduced the effectiveness of intensive (IT) ERP. Forty OCD patients received 15 sessions of ERP: 20 received daily treatment over 3 weeks and 20 received twice weekly therapy over 8 weeks. Results indicated that both programs were effective. The effect of therapy schedule was moderate, with a trend toward more improvement in the intensive group at posttreatment. No differences were found at follow-up; some evidence of relapse was found with IT but not TW.

Behavioral abnormalities in captive nonhuman primates.

In this study, we dealt with 11 species of nonhuman primates across 10 zoos in India. We recorded behavior as instantaneous scans between 9 a.m. and 5 p.m. In the study, we segregated behaviors for analyses into abnormal, undesirable, active, and resting. The 4 types of abnormal behavior exhibited included floating limb, self-biting, self-clasping, and stereotypic pacing. In the study, we recorded 2 types of undesirable behavior: autoerotic stimulation and begging. Langurs and group-housed macaques did not exhibit undesirable behaviors. A male lion-tailed macaque and a male gibbon exhibited begging behavior. autoerotic stimulation and self-biting occurred rarely. Males exhibited higher levels of undesirable behavior than did females. Animals confiscated from touring zoos, circuses, and animal traders exhibited higher levels of abnormal behaviors than did animals reared in larger, recognized zoos. The stump-tailed macaque was the only species to exhibit floating limb, autoerotic stimulation, self-biting, and self-clasping. Our results show that rearing experience and group composition influence the proportions of abnormal behavior exhibited by nonhuman primates in captivity. The history of early social and environmental deprivation in these species of captive nonhuman primates probably is critical in the development of behavioral pathologies. Establishing this will require further research.

Further evaluation of the role of protective equipment in the functional analysis of self-injurious behavior.

Using a procedure similar to the one described by Le and Smith (in press), we evaluated the effects of protective equipment during a functional analysis for 2 individuals who engaged in severe self-injurious behavior (SIB). Results of our analyses revealed that the use of protective equipment during functional analyses of SIB suppressed levels of responding such that a behavioral function could not be identified.

Models for assessing antipsychotics: antagonism of amphetamine-induced hyperactivity and stereotypies in mice.

All classical antipsychotics, such as chlorpromazine and haloperidol, have potent dopamine receptor-blocking properties. This unit describes the rat anti-Thy-1.1 model of acute proliferative glomerulonephritis for the study of chronic renal insufficiency. A procedure is detailed for the induction of glomerulonephritis in rats as well as measurement of daily urinary excretion of protein, which is a convenient, primary screening tool. The unit also provides methods for assessment of glomerular filtration rate and effective renal plasma flow in anesthetized rats with anti-Thy-1.1-induced renal insufficiency.

Design and synthesis of a morphine-6-succinyl-bovine serum albumin hapten for vaccine development.

A morphine-6-succinyl-BSA (M-6-S-BSA) hapten was designed in an effort to obtain a potent, long-lasting anti-morphine immune response for the treatment of morphine abuse. The analogue incorporated a succinic anhydride linker moiety in place of hydroxy group at C-6 of the morphine framework. Then morphine 6-hemisuccinate was conjugated to BSA in aqueous solution in the presence of water-soluble carbodi-imide. M-6-S-BSA was synthesized in three chemical steps starting from morphine sulphate, and the extent of conjugation was determined by base hydrolysis of the conjugate, extraction and measurement of free morphine. An average of 6.5 molecules of morphine were conjugated to each molecule of protein. Six male mice, Swiss White strain, immunized with various doses of the conjugate, were found to be producing antibody 8 weeks later, as determined by a modification of the (NH(4))(2)SO(4) method, which measures primary binding of antigen by antibody.

Modulation of cocaine-induced locomotor activity, rears and head bobs by application of WAY100635 into the dorsal and median raphe nuclei of the rat.

The present study investigated the role of somatodendritic 5-HT1A autoreceptors located in the dorsal and median raphe nuclei on the stimulant effect of cocaine on locomotor activity, rears and head bobs in female Glaxo Wistar rats. Cocaine was administered at a submaximal dose of 15 mg/kg i.p. to enable either a potentiation or attenuation to be observed. The selective 5-HT1A antagonist WAY100635 (0.21 ng or 21 ng) or saline was microinjected in the dorsal or median raphe nuclei followed by the peripheral administration of cocaine 60 min later. WAY 100635 microinjected in the dorsal or median raphe nuclei did not consistently alter the locomotor activity and the number of rears of saline-treated animals. Microinjection of WAY100635 in the dorsal raphe nucleus potentiated cocaine-induced locomotor activity and the number of head bobs. The number of rears induced by cocaine was not significantly altered by WAY100635 microinjected in the dorsal raphe nucleus. In contrast, microinjection of WAY100635 in the median raphe nucleus did not alter the stimulant effect of cocaine on locomotor activity, rears or head bobs. It may be suggested from these results that stimulation of somatodendritic 5-HT1A autoreceptors located in the dorsal raphe nucleus mediates an inhibitory effect on cocaine-induced locomotor activity and head bobs, whereas somatodendritic 5-HT1A autoreceptors in the median raphe nucleus are not involved in the inhibitory role of 5-HT on the stimulant effect of cocaine on locomotor activity and head bobs. A differential involvement of the midbrain raphe nuclei may exist controlling the stimulant effect of cocaine on locomotor activity and head bobs.

Fluoxetine blocks expression but not development of sensitization to morphine-induced oral stereotypy in rats.

RATIONALE: Repeated high doses of morphine in the rat cause stereotypic gnawing behavior that can be re-expressed by a low dose of morphine weeks and even months after the initial treatment. The determination of the role of serotonin in this sensitized morphine-induced behavior has both empirical and theoretical relevance. OBJECTIVES: To determine whether the serotonin-reuptake blocker fluoxetine will block the development and/or the expression of this opiate-induced stereotypy. METHODS: Rats were given four 10-mg/kg injections of morphine alone or with 5.0 mg/kg fluoxetine over a 36-h period. At weekly intervals for 6 weeks after the last of the sensitizing morphine doses, all rats were challenged with 4.0 mg/kg morphine. At week 2 and week 4, however, the morphine was co-administered with fluoxetine. RESULTS: Fluoxetine completely blocked the expression of the morphine-induced stereotypy; however, when the morphine/fluoxetine-treated rats were challenged with morphine alone, they expressed similar degrees of stereotypy as the rats that initially only received morphine. CONCLUSIONS: The results indicate that increasing synaptic serotonin will block the expression but not the development of sensitization to the oral stereotypic effects of repeated high doses of morphine. Also, despite the complete blocking of the morphine effect by fluoxetine during the sensitization phase, the presence of significant biting by these rats during the challenge with morphine alone argues that conditioning factors are not a necessary component for the morphine sensitization to develop.

Dynamics of self-injurious behaviors.

Self-injurious behavior was examined in a case study of head-banging by an 8-year-old girl with profound mental retardation and an autistic disorder. Trajectories of the arm movements and impact forces of the head blows were determined from a dynamic analysis of videotapes. Results revealed a high degree of cycle-to-cycle consistency in the qualitative dynamics of the limb motions, with one hand motions being faster than those with two hands (inphase and antiphase) and the motions with the helmet about 25% faster than those without the helmet. The impact force of SIBs as a percentage of body weights are near the low end of forces generated in boxing blows and karate hits.