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Query: UMLS:C0004352 (autism)
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Behavioral side effects associated with clonazepam may include agitation, aggression, hyperactivity, irritability, property destruction, and temper tantrums. These side effects may be inadvertently confused with other behavioral or psychiatric conditions, especially if exacerbation of existing challenging behavior occurs. This report describes an individual with mental retardation who experienced behavioral exacerbation associated with clonazepam prescribed at 2 mg/day (0.02 mg/kg/day) to treat aggression, self-injurious behavior, property destruction, and screaming, which was measured with a 15-minute partial interval recording measurement method. When clonazepam was reduced and discontinued, these behaviors significantly decreased from 3.1% of intervals (95% confidence band = 1.6% to 4.6%) to 0.1% of intervals (95% confidence band = 0% to 0.1%). Indicators suggesting review by appropriate medical personnel for possible clonazepam behavioral side effects are provided.
J Autism Dev Disord 2003 Jun
PMID:Brief report: clonazepam behavioral side effects with an individual with mental retardation. 1290 37

A meta-analysis of prevalence and cohort studies conducted over the last 30 years was carried out to identify risk markers for challenging behaviour shown by individuals with intellectual disabilities (IDs). A total of 86 potential studies was identified from the review, with 22 (25.6%) containing sufficient data to enable a statistical analysis to be conducted. Results indicated that males were significantly more likely to show aggression than females, and that individuals with a severe/profound degree of ID were significantly more likely to show self-injury and stereotypy than individuals with a mild/moderate degree of ID. Individuals with a diagnosis of autism were significantly more likely to show self-injury, aggression and disruption to the environment whilst individuals with deficits in receptive and expressive communication were significantly more likely to show self-injury. In most cases, tests for heterogeneity were statistically significant, as expected. The meta-analysis highlighted the paucity of methodologically robust studies of risk markers for challenging behaviours and the lack of data on incidence, prevalence and chronicity of challenging behaviour in this population.
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PMID:Risk markers associated with challenging behaviours in people with intellectual disabilities: a meta-analytic study. 1291 91

The title of this contribution involves two consecutive questions: have the effects of medication in autism indeed been disappointing? And if so, why? The answer to the first question depends on whether one focuses on the core social and communicative deficits of autism, or on various complicating behaviour problems. Attempts over the past decades to develop drugs that specifically improve social and communicative functioning have failed. Among the most ambitious attempts were medical interventions in the endogenous opioid system that were motivated from animal models on the involvement of this system in various aspects of social behaviour. By contrast, medications such as the newer antipsychotics, psychostimulants, presynaptic noradrenergic blocking agents (clonidine and guanfacine) and selective serotonin reuptake inhibitors were shown to reduce impairing complicating symptoms of affective instability, irritability, hyperactivity and inattentiveness, aggression, self-injury and stereotypies. The explanation for the medication-refractory status of social and communicative deficits should be sought in at least two related factors: (1) the as yet unidentified neurochemical basis of autism, and (2) the obvious lack of involvement of the main neurotransmitter systems (dopamine, noradrenaline and serotonin) in the pathophysiology of social and communicative behaviour.
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PMID:Why have drug treatments been so disappointing? 1452 Nov 96

Autism is a lifelong, severe, developmental disorder that appears initially in infancy and early childhood and impairs the acquisition of some of the most important skills in human life. The disease is characterized by impaired social interactions, verbal and nonverbal communication deficiencies, limited activities and interest, and repetitive behaviors. Often accompanying the disorder are behavioral disturbances, such as self-mutilation and aggression, psychiatric symptoms, and seizures, which necessitate the administration of multiple medications to help the affected individual participate effectively in the educational and rehabilitative process. Dentists caring for these people must be familiar with the manifestations of the disease and its associated features so that they can garner the maximum level of cooperation. They must also be familiar with the medications used to treat the associated features of the disorder because many of these pharmaceuticals cause untoward orofacial and systemic reactions and may precipitate adverse interactions with dental therapeutic agents.
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PMID:The pathophysiology, medical management, and dental implications of autism. 1456 Aug 72

Reeler (rl/rl) and reeler/wild-type (+/rl) mice synthesize Reln at subnormal rates, as do patients with schizophrenia, bipolar disorder, and autism, thereby forming the basis for a Reln hypothesis for vulnerability to these psychopathologies and justifying attention to the behavioral phenotypes of Reln-deficient mice. Tests of gait, emotionality, social aggression, spatial working memory, novel-object detection, fear conditioning, and sensorimotor reflex modulation revealed the behavioral phenotype of rl/rl, but not +/rl, mice to be different from that of wild-type (+/+) mice. These results reveal no effect of Reln gene dosage and provide significant challenges to both the Reln and the neurodevelopmental hypotheses of the etiology of major psychopathologies.
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PMID:Behavioral phenotype of the reeler mutant mouse: effects of RELN gene dosage and social isolation. 1467 45

To describe lifetime mental disorders among perpetrators of severe inter-personal crimes and to identify the problem domains most closely associated with aggression and a history of repeated violent criminality, we used structured interviews, clinical assessments, analyses of intellectual functioning, medical and social files, and collateral interviews in 100 consecutive subjects of pretrial forensic psychiatric investigations. Childhood-onset neuropsychiatric disorders [attention-deficit/hyperactivity disorder (AD/HD), learning disability, tics and autism spectrum disorders] affected 55% of the subjects and formed complex comorbidity patterns with adult personality disorders [including psychopathic traits according to the Psychopathy Checklist (PCL-R)], mood disorders and substance abuse. The closest psychiatric covariates to high Lifetime History of Aggression (LHA) scores and violent recidivism were the PCL-R scores and childhood conduct disorder (CD). Behavioral and affective PCL-R factors were closely associated with childhood AD/HD, CD, and autistic traits. The results support the notion that childhood-onset social and behavioral problems form the most relevant psychiatric symptom cluster in relation to pervasive adult violent behavior, while late-onset mental disorders are more often associated with single acts of violent or sexual aggression.
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PMID:Adult psychopathic personality with childhood-onset hyperactivity and conduct disorder: a central problem constellation in forensic psychiatry. 1467 46

Apart from control of the seizures, two of the most important factors in determining how well a child with epilepsy progresses toward independence are cognition and behavior. The diagnosis of the correct epilepsy syndrome often provides information with regard to probability of good seizure control and intellectual outcome. However, relatively little has been published on the behavioral aspects of the various epilepsy syndromes. In West syndrome there is emerging evidence that early effective treatment might improve outcome in terms of both cognition and behavior. The work on this syndrome in children with tuberous sclerosis has demonstrated an association between temporal lobe tubers and autism. In Dravet syndrome, a variety of psychiatric disorders have been reported, including hyperactivity and autistic features. This is another epilepsy syndrome that tends to be resistant to treatment, implying that the prognosis has to be guarded. The behavioral problems reported with Lennox-Gastaut syndrome also include autistic features, as well as generally sluggish behavior. It is very likely that these characteristics largely reflect the effect of ongoing seizure activity. Autistic features, aggression, and hyperkinesis have been described with Landau-Kleffner syndrome. The behavior may improve dramatically with appropriate medical treatment or after multiple subpial transection. Although the syndrome of benign partial seizures with centrotemporal or rolandic spikes is said to have a very good prognosis, it is becoming increasingly evident that behavioral problems such as concentration difficulties, tempers, hyperactivity, and impulsivity might occur. Juvenile myoclonic epilepsy has been associated with very variable behavioral traits, sometimes with immature personality features and poor social adjustment suggesting frontal lobe dysfunction. Because many of the reports of behavioral disturbance associated with epilepsy syndromes are anecdotal and do not include validated measures of behavior it would be unwise to draw firm conclusions from them at this stage. Carefully conducted prospective studies, paying particular attention to any behavioral improvements that occur with successful treatment of the epilepsy, are required.
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PMID:Behavioral aspects of pediatric epilepsy syndromes. 1472 41

This investigation provides a preliminary examination of the difference between programmed and obtained reinforcement rates and its potential influence during treatment of aggression in a natural setting. Following a functional analysis that suggested that the aggression of a boy with autism was negatively reinforced, intervention was implemented by the boy's mother. Concurrent fixed-ratio (FR) 1 FR 1 schedules of escape were arranged for manding and aggression. When mands failed to compete effectively with aggression, obtained reinforcement ratios were calculated; these indicated that obtained reinforcement varied from the programmed schedule for aggression but not for mands. Increasing the rate of prompts for mands resulted in an increase in mands and a decrease in aggression to near-zero levels.
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PMID:Obtained versus programmed reinforcement practical considerations in the treatment of escape-reinforced aggression. 1529 45

The efficacy of antiepileptic drugs (AEDs) and psychotropic medications in children with autism is limited to the treatment of seizures or to specific behaviors such as irritability, impulsivity, hyperactivity, repetitive behaviors, or aggression. The reliability and value of the available data--to determine the efficacy of these medications in autism--are limited by lack of controlled clinical trials, the small number of subjects, the heterogeneity of the population studied, and the brief duration of most drug trials. Indeed, few controlled clinical trials using AEDs in autism, with or without seizures, have been conducted. Because some AEDs also have a positive effect on mood, the benefits that children with autism sometimes obtain from these medications may not be due to the treatment of the abnormal electrical activity or the seizures per se but to an effect on common neuronal systems responsible for both behavior and epilepsy. The relationship between epilepsy and autism, and specifically the effects that abnormal electrical activity may have on the developing brain, may provide some valuable insights into the type of studies that are needed to help us understand the pathophysiology of autism.
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PMID:AEDs and psychotropic drugs in children with autism and epilepsy. 1536 71

The olfactory bulb plays a critical role in odor discrimination and in processing olfactory cues controlling social behavior in mammals. Given that the pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1) is highly expressed in the olfactory bulb, we examined its role in regulating olfaction and social investigation. We found that olfactory detection of nonsocial stimuli was similar in PAC1-deficient mice and wild-type (WT) littermates. In contrast, PAC1-deficient mice displayed markedly abnormal social behaviors. PAC1-deficient mice exhibited a faster decrease in social investigation after repeated exposure to social cues or ovariectomized female urine compared with WT mice. Moreover, PAC1-deficient females exhibited delayed affiliative behavior when housed with novel males, and PAC1-deficient males displayed excessive sexual mounting toward both females and males as well as reduced aggression and increased licking and grooming toward intruder males. In aggregate, these results uncover PAC1 signaling as an important factor in the development and/or functioning of neural pathways associated with pheromone processing and the regulation of social interactions in mice. In turn, these studies raise the potential clinical relevance of PACAP signaling dysfunctions in neuropsychiatric disorders characterized by social reciprocity impairments such as autism spectrum disorders.
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PMID:Altered social behavior in pituitary adenylate cyclase-activating polypeptide type I receptor-deficient mice. 1547 Jan 44


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