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Engagement in challenging behaviour (e.g., aggression, self-injury) is reported to occur in neurodevelopmental disorders such as intellectual disabilities (ID), autism spectrum disorder (ASD), and fragile X syndrome (FXS). Common interventions to address these behaviours include both behavioural and pharmacological approaches. Although psychotropic medications are commonly used to address challenging behaviour in ID, ASD, and FXS, demonstration of the effectiveness of treatment is limited. Furthermore, research examining interaction effects between psychotropic medication, challenging behaviour, and environmental events within specific neurodevelopmental disorders such as ID, ASD, and FXS is scarce. The purpose of this chapter is to provide an overview of challenging behaviour within ID, ASD, and FXS and of the effectiveness of psychotropic medication as an intervention for challenging behaviour within these neurodevelopmental disorders. Finally, research examining how psychotropic medication may impact the relationship between challenging behaviour and environmental events is reviewed.
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Trastorno del Espectro Autista , Síndrome del Cromosoma X Frágil , Discapacidad Intelectual , Humanos , Trastorno del Espectro Autista/tratamiento farmacológico , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Discapacidad Intelectual/tratamiento farmacológico , Psicotrópicos/uso terapéutico , AgresiónRESUMEN
INTRODUCTION: Psychotropic medication is often prescribed to individuals with intellectual and developmental disabilities who engage in challenging and other behavior (e.g., aggression and stereotypy, respectively), but there is limited understanding of the effects of these medications on behavior. OBJECTIVE: Within the context of a larger study that evaluated the effects of psychotropic medication regimen changes on the presentation of challenging behavior, this study describes the presentation of stereotypic behavior of three individuals diagnosed with autism spectrum disorder. METHODS: Stereotypy was measured during weekly, one-hour, direct observations and during the control and ignore conditions of functional analyses of challenging behavior (which were conducted following changes in psychotropic medication regimens). RESULTS: Patterns of stereotypy varied over time, but not significantly, and at times seemed to coincide with medication changes. DISCUSSION: Our results suggest stereotypy persists throughout adulthood; however, additional research is needed.
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Trastorno del Espectro Autista , Trastorno de Movimiento Estereotipado , Adulto , Agresión , Trastorno del Espectro Autista/tratamiento farmacológico , Humanos , Psicotrópicos/uso terapéutico , Conducta Estereotipada , Trastorno de Movimiento Estereotipado/tratamiento farmacológicoRESUMEN
RATIONALE: Fragile X syndrome (FXS), the most prevalent genetic form of intellectual disability, is characterized by intellectual impairment, impaired sociability, aggression, self-injury, hyperactivity, and attention deficits. A consequence of the hyperactivity and attention deficits is that individuals with FXS are frequently diagnosed with attention deficit hyperactivity disorder (ADHD) and treated with medications approved for ADHD (e.g., the α2-agonist clonidine). The pharmacotherapy of FXS is often accompanied with behavioral therapies that rely on positive reinforcement and other operant principles. Despite the commonplace mixture of drug and behavioral therapy, little attention has been paid to the observation that clonidine or other psychotropic drugs may alter operant processes. OBJECTIVES: In the present progressive ratio study, we used a knockout mouse model to test the effects of the fragile X genotype, the α2-agonist clonidine, and the fragile X genotype and clonidine together on operant processes in a positive reinforcement task. RESULTS: We found that clonidine decreased the progressive ratio breakpoint, increased the length of post-reinforcement pauses, and slowed the run rate. None of these effects varied by genotype. The effect on breakpoint suggests that clonidine alters motivation, but analysis using mathematical principles of reinforcement (MPR) did not rule out motor parameters as a contributor. CONCLUSIONS: Our findings show that clonidine alters operant behavior and serve as a caution for combining clonidine with behavioral therapies that rely on positive reinforcement. Further research using different murine behaviors (e.g., touchscreen tasks) or different animal models (e.g., knockout rats) is needed to explore the interaction between pharmaco- and behavioral therapy.
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Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Clonidina/farmacología , Condicionamiento Operante/efectos de los fármacos , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Esquema de Refuerzo , Animales , Síndrome del Cromosoma X Frágil/psicología , Genotipo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Motivación/efectos de los fármacos , RecompensaRESUMEN
OBJECTIVES: A paucity of information exists relating to the possible biological and environmental interactions influencing the occurrence of stereotypical behavior. In particular, there is limited research on the effects of psychotropic medication use on stereotypy presentation in individuals diagnosed with developmental disabilities such as intellectual disability and autism spectrum disorder. METHODS: We studied the stereotypy of a man with autism spectrum disorder and intellectual disability across 2 years. The topographies of stereotypical behavior included walking in circles, head tapping, arm flinging, and object stereotypy. These behaviors were observed weekly while the participant received daily dosages of 25 mg of chlorpromazine, 1.5 mg of lorazepam, and 2,500 mg of divalproex. At Week 75, chlorpromazine was discontinued while the other drugs and dosages were maintained. RESULTS: We observed a statistically significant decrease in walking in circles, but no changes in the other topographies of stereotypy. CONCLUSIONS: The results suggest that the gross motor activity was differentially affected by the chlorpromazine discontinuation and also suggests that alterations in dopamine receptor binding may have selectively influenced changes in stereotypical responding.
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INTRODUCTION: The purpose of this study was to gain additional insight on patterns of behavior of three individuals dually diagnosed with Intellectual disability (ID) and Bipolar disorder as they cycled between elevated and depressed mood states. METHODS: Data were collected from weekly, one hour observations across a period of several months. The total duration of time spent engaged in target responses (pacing, rocking, and talking), in addition to indirect measures of activity (irritability and hyperactivity subscale of the Aberrant Behavior Checklist-Community; ABC-C), were assessed to characterize and monitor changes in overall state. RESULTS: While observable behavior seemed to be a good indicator of overall state, ABC-C irritability and hyperactivity subscales were not. Additional analyses included lag sequential analyses of environmental stimuli and conditions potentially correlated with observed behavior. CONCLUSIONS: Our findings suggest that observable behavior may be one way to monitor the progression of Bipolar disorder in those with ID; however, further research needs to be conducted.
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Self-injurious behavior (SIB) presents unique challenges as researchers have identified that some SIB may be resistant to treatment. The unit of analysis in this research is often the frequency of behavior with relatively little attention devoted to the analysis of inter-response time relations. We assessed whether changes in the rate of SIB were also associated with changes in the temporal distribution of this behavior in the presence and absence of systematically manipulated environmental variables. This study included three participants diagnosed with profound intellectual disabilities who engaged in SIB maintained by both negative and automatic reinforcement. For two of the participants, we used a multiple baseline design across participants to assess the effects of noncontingent access to preferred activities on both the rate and temporal distribution of SIB. For the third participant, we used a reversal design to assess the effects of a change in daily schedule (i.e., attending or not attending work) on the rate and temporal distribution of SIB. For all three participants, antecedent manipulations decreased the rate of SIB; however, operant contingency values (a measure of temporal distribution) did not change in a corresponding fashion. These data suggest that although antecedent manipulations may decrease the overall rate of the behavior, once SIB is emitted, additional instances are likely to occur close together in time.
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Psychotropic medications are often prescribed to reduce challenging behavior in individuals with intellectual and developmental disabilities (IDD). Functional analyses (FAs) have demonstrated utility in assessing medication impact on behavior; however, the impact of adverse side effects (ASE) on challenging behavior is under-assessed. The purpose of this study was to develop a methodology, similar to FAs, to explore potential medication ASE impact on challenging behavior in seven individuals with IDD. Results revealed response rate differences in designed ASE conditions for most participants. Outcomes support further development and use of this methodology to assess the presence and impact of ASEs.
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OBJECTIVE: The use of psychotropic medication to address challenging behavior in individuals diagnosed with intellectual disabilities is common practice; however, very few studies have examined how multiple medication use (or combination treatment) impacts the behaviors these medications are prescribed to treat. METHOD: The current study followed eight individuals over a two-year period as they experienced changes in their psychotropic medication regimens. During that time, data from functional analyses and indirect assessments of challenging behavior were collected. RESULTS: The results suggest that changes in psychotropic medication regimens can produce changes in functional assessment outcomes, suggesting a need for continued behavioral assessment to better inform medication practices and behavioral treatment. Of the eight participants in the study, five participants' behaviors varied in rate of responding in FAs across all medication changes. Additionally, three participants' FAs produced changes in outcomes; however, those changes were not consistent across all medication changes, that is, not every medication change yielded different outcomes from previous assessments. CONCLUSION: This study demonstrates how the outcome of an FA can be used to monitor the effects of psychotropic medication changes, specifically when medications are combined, on challenging behavior in individuals with intellectual and developmental disabilities.
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In working with individuals with intellectual and developmental disabilities (IDDs), it is direct care staff who are often required to collect data on individuals' behavior which is used as the basis for implementation of empirically based approaches for intervention and treatment. Due to limited resources, indirect and descriptive measures of challenging behaviors are employed to analyze the function of individuals' behaviors in place of the preferred method of multimodal assessment, which includes experimental functional analysis. To ensure the most effective services and support to individuals with IDDs, accurate and consistent data collection is critical. In this article, we highlight the importance of accurate data collection practices, conduct a comparison of data collection methods, and discuss limitations . and barriers for staff. The article concludes with recommendations for best practices and future research.
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Recolección de Datos/normas , Discapacidades del Desarrollo , Investigación sobre Servicios de Salud/normas , Discapacidad Intelectual , Problema de Conducta , HumanosRESUMEN
Fragile X syndrome (FXS), a disorder caused by a mutation in the FMR1 gene, is often associated with Attention Deficit Hyperactivity Disorder (ADHD). Common treatments for the hyperactivity often seen in ADHD involve the use of stimulants and α2-adrenergic agonists. The Fmr1 knockout (KO) mouse has been found to be a valid model for FXS both biologically and behaviorally. Of particular interest to our research, the Fmr1 KO mouse has been demonstrated to show increased locomotion in comparison to wild type (WT) littermates. In the present study, we assessed the effects of clonidine (0.05 mg/kg) and methylphenidate (5 mg/kg) on motor activity in Fmr1 KO mice and their WT littermates in the open field test. Results showed that methylphenidate increased motor activity in both genotypes. Clonidine decreased motor activity in both genotypes, but the effect was delayed in the Fmr1 KO mice.
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Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Estimulantes del Sistema Nervioso Central/farmacología , Clonidina/farmacología , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Metilfenidato/farmacología , Actividad Motora/efectos de los fármacos , Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Animales , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/psicología , Estimulantes del Sistema Nervioso Central/uso terapéutico , Clonidina/uso terapéutico , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/psicología , Metilfenidato/uso terapéutico , Ratones NoqueadosRESUMEN
Recent research has established that many children and adult diagnosed with autism experience gastrointestinal symptoms. Furthermore, research has demonstrated that gastrointestinal symptoms can impact drug availability and absorption. In this paper we explore the presence of gastrointestinal symptoms in autism and put forth a call for a formal evaluation of the potential relationship between gastrointestinal symptoms and psychotropic medication effectiveness in individuals with autism.
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Trastorno Autístico/tratamiento farmacológico , Enfermedades Gastrointestinales/fisiopatología , Psicotrópicos/uso terapéutico , Adulto , Trastorno Autístico/complicaciones , Niño , Ensayos Clínicos como Asunto/métodos , Enfermedades Gastrointestinales/etiología , Humanos , Psicotrópicos/farmacocinéticaRESUMEN
Deleting the tailless (TLX) gene in mice produces a highly aggressive phenotype yet to be characterized in terms of heterozygous animals or neurotransmitter mechanisms. We sought to establish pharmacological control over aggression and study the role of serotonin (5-HT)(2A/C) receptors in mediating changes in aggression. We analyzed aggression in mice heterozygous (+/-) or homozygous (-/-) for the TLX gene and wild-types (+/+) using a resident-intruder paradigm. No +/+ mice were aggressive, 36% of +/- TLX and 100% of -/- TLX mice showed aggression. Dose-effect functions were established for clozapine (0.1-1.5mg/kg, ip), ketanserin (0.3-1.25 mg/kg, ip), and (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(±)DOI] (0.5-2.0 mg/kg, ip). Injecting clozapine decreased the frequency and duration of attacks for +/- TLX and -/- TLX mice. Clozapine did not decrease grooming in either +/- TLX or -/- TLX mice but may have increased locomotion for -/- TLX mice. Injecting ketanserin, a 5-HT(2A/C) receptor antagonist, produced differential decreases in frequency and latency to aggression between genotypes and corresponding increases in locomotor behavior. Injecting (±)DOI, a 5-HT(2A/C) receptor agonist, increased the frequency and duration of attacks, decreased the latency to attacks, and decreased locomotion in +/- and -/- TLX mice. Results of the current study suggest aggression displayed by TLX null and heterozygous mice involves 5-HT(2A/C) receptors.
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Agresión/fisiología , Receptor de Serotonina 5-HT2A/metabolismo , Receptor de Serotonina 5-HT2C/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Agresión/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Clozapina/farmacología , Ketanserina/farmacología , Masculino , Ratones , Ratones Noqueados , Actividad Motora/efectos de los fármacos , Fenotipo , Receptores Citoplasmáticos y Nucleares/genética , Agonistas del Receptor de Serotonina 5-HT2/farmacología , Antagonistas del Receptor de Serotonina 5-HT2/farmacologíaRESUMEN
Social behavior abnormalities in Fragile X syndrome (FXS) are characterized by social withdrawal, anxiety, and deficits in social cognition. To assess these deficits, a model of FXS, the Fmr1 knockout mouse (Fmr1 KO), has been utilized. This mouse model has a null mutation in the fragile X mental retardation 1 gene (Fmr1) and displays physical and behavioral characteristics similar to humans with FXS. Several studies have investigated the social behavior of this model, but the results on the behavioral phenotype have not been consistent. In order to further characterize the social behavior in the knockout, isolation-reared Fmr1 KO were evaluated to determine if they differ in their social behavior compared to wild-type littermate controls. Differences by genotype were not observed in social approach behavior; however, the knockout mice showed a significantly reduced preference for social novelty and decreased sniff time in the sociability phase. These findings add to the growing body of knowledge on the subtle differences in social behavior shown by the Fmr1 knockout mice, and that differences occur when the subjects are isolation-reared. Validity of the model and possible changes to methodology are discussed.
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Conducta Animal/fisiología , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Conducta Social , Animales , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Reproducibilidad de los Resultados , Aislamiento SocialRESUMEN
A thermal preference task was used to assess the effects of sleep deprivation on nociceptive behavior using hot and cool stimuli. The thermal preference apparatus allowed male rats to move freely from a hot thermal plate (44.7°C) to an adjacent plate at neutral (33.5°C) or cold temperatures (1.3-11°C). Investigators recorded occupancy on the colder side, frequency of movements between the 2 compartments, and first escape latency from the cold side. Parametric analysis of thermal preference indicated that behavioral allocation was related to temperature ranges previously associated with activation of thermal nociceptors. A 50% occupancy rate was determined from a stimulus-response function identifying 1.3°C vs. 44.7°C as optimal temperatures. This temperature combination was then used to test the effects of sleep deprivation for 48h using the pedestal-over-water method on response allocation to the 2 temperature zones. Sleep deprivation decreased time spent on the cooled plate. Cumulative occupancy indicated differential effects for sleep deprivation with the rats preferring to remain on the hot side vs. the cold side, suggesting that sleep deprivation increased the nociceptive properties of the cold stimulus.
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Dimensión del Dolor/métodos , Umbral del Dolor/fisiología , Dolor/fisiopatología , Privación de Sueño/fisiopatología , Sensación Térmica/fisiología , Animales , Frío/efectos adversos , Calor/efectos adversos , Masculino , Fibras Nerviosas Mielínicas/fisiología , Fibras Nerviosas Amielínicas/fisiología , Nociceptores/fisiología , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/fisiologíaRESUMEN
We analyzed the effects of four conventional antiepileptic drugs (AEDs) - carbamazepine (CBZ), ethosuximide (ETH), phenytoin (PHT), and valproate (VPA) - on operant behavior maintained by negative or positive reinforcement contingencies. Rats were trained to lever press on a free-operant avoidance schedule or variable-interval (VI) schedule of appetitive reinforcement. Dose-effect functions were separately established on each reinforcement contingency for CBZ (12.5-100 mg/kg), ETH (25-200 mg/kg), PHT (12.5-50 mg/kg), and VPA (50-400 mg/kg). CBZ and PHT reduced responding on free-operant avoidance and VI appetitive reinforcement tasks, with positively reinforced behavior reduced at lower drug dosages than negatively reinforced responding. ETH and VPA reduced responding on the VI appetitive reinforcement task, but did not alter behavior maintained on the free-operant avoidance schedule. Our results suggest that conventional AEDs vary in their effect on operant behavior, depending on the type of reinforcement process maintaining responding.
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Anticonvulsivantes/farmacología , Condicionamiento Operante/efectos de los fármacos , Refuerzo en Psicología , Análisis de Varianza , Animales , Conducta Animal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
This review discusses the laboratory and clinical research supporting the rationale for the efficacy of donepezil (Aricept USA) in enhancing cognition in autism, Alzheimer disease, Down syndrome, traumatic brain injury, Attention Deficit Hyperactivity Disorder (ADHD), and schizophrenia. While preliminary animal models have shown effective, human studies exclusive of Alzheimer disease are sparse. Although attention and memory are unlikely a sole operation of the cholinergic system, evidence indicates a promising direction for further examination of this hypothesis in autism. Studies that examine changes in operationally defined behaviors and reliable and valid measure of changes in attention and memory are needed.
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Trastorno Autístico/tratamiento farmacológico , Indanos/uso terapéutico , Discapacidades para el Aprendizaje/tratamiento farmacológico , Trastornos de la Memoria/tratamiento farmacológico , Recuerdo Mental/efectos de los fármacos , Nootrópicos/uso terapéutico , Piperidinas/uso terapéutico , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/psicología , Animales , Atención/efectos de los fármacos , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/psicología , Trastorno Autístico/diagnóstico , Trastorno Autístico/psicología , Lesiones Encefálicas/diagnóstico , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/psicología , Donepezilo , Síndrome de Down/diagnóstico , Síndrome de Down/tratamiento farmacológico , Síndrome de Down/psicología , Humanos , Indanos/efectos adversos , Discapacidades para el Aprendizaje/diagnóstico , Discapacidades para el Aprendizaje/psicología , Trastornos de la Memoria/diagnóstico , Trastornos de la Memoria/psicología , Nootrópicos/efectos adversos , Piperidinas/efectos adversos , Esquizofrenia/diagnóstico , Esquizofrenia/tratamiento farmacológico , Resultado del TratamientoRESUMEN
The purpose of this paper is to provide a brief review of current research in fragile X syndrome (FXS) with regards to the morphology and behavioral phenotype associated with FXS and the use of psychotropic medication for the treatment of behavior problems (e.g., aggression) often seen in FXS (full mutation). The lack of production of the fragile X mental retardation protein (FMRP) is associated with FXS and has been found to result in various neuronal changes such as altered dendritic morphology and function as well as altered neurotransmitter functions. A review of the basic literature on animal models and the relevance of these findings for the use of psychotropic treatment of problem behaviors in FXS will be discussed. Future research directions will be presented.
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Investigación Biomédica/tendencias , Ensayos Clínicos como Asunto/tendencias , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/tendencias , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Psicotrópicos/uso terapéutico , Animales , Síndrome del Cromosoma X Frágil/fisiopatología , Humanos , Resultado del TratamientoRESUMEN
Risperidone has shown safety and efficacy for aggressive and destructive behaviors in short-term studies. This longer-duration study includes a broad sample. Forty subjects, aged 8-56 years (mean=22), all with mental retardation and 36 with autism spectrum disorders participated in this 22-week crossover study, with 24 weeks of open maintenance thereafter. Of 40 subjects, 23 (57.5%) responded fully (50% decrease in Aberrant Behavior Checklist-Community Irritability subscale score), while 35 subjects (87.5%) showed a 25% decrease. Gender, mood disorder, and antiseizure medications did not alter response. Increased appetite and weight gain were common. Low dose risperidone was effective for aggressive behavior in persons with MR. More long-term studies are needed, incorporating weight control interventions.