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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aggression, self-injury, and mood disturbances in persons with autistic disorders, while not uncommon, do not constitute core features of autism. Moreover, these problems can occur for a variety of reasons, which need to be assessed in order to plan appropriate and frequently combined (behavioral-pharmacological) treatments. Drugs acting primarily in the dopaminergic, serotonergic, adrenergic, opioidergic, and glutamatergic systems all have been explored in the treatment of aggression and self-injury. While no single drug or class of medication has yet emerged as consistently effective, a number of drugs appear promising. Advances in the assessment of aggressive behaviors, the identification of predictors of drug response, and additional controlled clinical drug trials specifically aimed at these target behaviors are essential in improving the approach to these problematic behaviors in the context of autistic disorder.
J Autism Dev Disord 2000 Oct
PMID:Pharmacological treatment of mood disturbances, aggression, and self-injury in persons with pervasive developmental disorders. 1109 82

Serotonin (5-hydroxytryptamine, 5-HT) appears to play a role in the pathophysiology of a range of neuropsychiatric disorders, and serotonergic agents are of central importance in neuropharmacology. Genes encoding various components of the 5-HT system are being studied as risk factors in depression, schizophrenia, obsessive-compulsive disorder, aggression, alcoholism, and autism. Recently, pharmacogenetic research has begun to examine possible genetic influences on therapeutic response to drugs affecting the serotonin system. Genes regulating the synthesis (TPH), storage (VMAT2), membrane uptake (HTT), and metabolism (MAOA) of 5-HT, as well as a number of 5-HT receptors (HTR1A, HTR1B, HTR2A, HTR2C, and HTR5A), have been studied and this initial research is reviewed here. After a brief introduction to serotonin neurobiology and a general discussion of appropriate genetic methodology, each of the major 5-HT-related genes and their encoded proteins are reviewed in turn. For each gene, relevant polymorphisms and research on functional variants are discussed; following brief reviews of the disorder or trait association and linkage studies, pharmacogenetic studies performed to date are covered. The critical and manifold roles of the serotonin system, the great abundance of targets within the system, the wide range of serotonergic agents-available and in development-and the promising preliminary results suggest that the serotonin system offers a particularly rich area for pharmacogenetic research.
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PMID:Pharmacogenetics and the serotonin system: initial studies and future directions. 1113 68

Recent advances in pharmacological treatment of severe behavior disorders in persons with developmental disabilities suggest the use of antidepressant medication for therapeutic management. This research evaluated two antidepressant medications for treatment-resistant aggression and self-injury exhibited by two persons with developmental disabilities. Behavioral assessment data documented that sertraline (a serotonin selective reuptake inhibitor) was effective in reducing self-injurious behaviors in a 20-year-old man with severe mental retardation and clomipramine (a tricyclic antidepressant) was associated with the elimination of aggressive behavior in a 14-year-old boy with autism. Clinical effects from the medications were measured in relation to and shown to be a function of dosage level. Extended follow-up assessments revealed maintenance of treatment gains with continued medication administration.
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PMID:Therapeutic effects and long-term efficacy of antidepressant medication for persons with developmental disabilities. Behavioral assessment in two cases of treatment-resistant aggression and self-injury. 1115 86

Although the core features of autism do not change qualitatively, a gradual overall symptomatic improvement including an increase in adaptive skills is observed in most cases with age. Follow-up studies show that the diagnostic features, the differential diagnosis, and clinical problems of adult autistics differ substantially from that of autistic children. The differential diagnosis of older autistics include personality disorders, learning disabilities, and mood disorder. Depression, epilepsy, and behavioral problems such as aggression and agitation may be major clinical problems during adolescence. The early indicators of a better outcome include a higher level of IQ and language. Among the neuropsychological variables, measures of flexibility and cognitive shift are important as prognostic factors. Early behavioral and educational intervention may especially increase the adaptive skills of the patients and promote the in-family communication. The outcome studies of autism are particularly helpful in addressing the appropriate and most effective programs of remediation for adult autistics.
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PMID:Infantile autism: adult outcome. 1129 Oct 11

Fragile X syndrome is the most prevalent cause of mental retardation. It is usually caused by the transcriptional inactivation of the FMR-1 gene. Although the cognitive defect is the most recognized symptom of fragile X syndrome, patients also show behavioral problems such as hyperarousal, hyperactivity, autism, aggression, anxiety and increased sensitivity to sensory stimuli. Here we investigated whether fragile X mice (fmr-1 gene knockout mice) exhibit abnormal sensitivity to sensory stimuli. First, hyperreactivity of fragile X mice to auditory stimulus was indicated in the prepulse inhibition paradigm. A moderately intense prepulse tone, that suppresses startle response to a strong auditory stimulus, elicited a significantly stronger effect in fragile X than in control mice. Second, sensory hyperreactivity of fragile X mice was demonstrated by a high seizure susceptibility to auditory stimulation. Selective induction of c-Fos, an early-immediate gene product, indicated that seizures involve auditory brainstem and thalamic nuclei. Audiogenic seizures were not due to a general increase in brain excitability because three different chemical convulsants (kainic acid, bicuculline and pentylenetetrazole) elicited similar effects in fragile X and wild-type mice. These data are consistent with the increased responsiveness of fragile X patients to auditory stimuli. The auditory hypersensitivity suggests an abnormal processing in the auditory system of fragile X mice, which could provide a useful model to study the molecular and cellular changes underlying fragile X syndrome.
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PMID:Fragile X mice develop sensory hyperreactivity to auditory stimuli. 1130 Dec 11

There are no aetiologically-based treatments available to cure autism. Though psychotropics have a role in the management of some symptoms of autism, clinical trial evidence for the use of psychotropics is in its infancy and needs close monitoring. About half of the subjects with high functioning pervasive developmental disorders (PDDs) are currently reported to be on psychotropics (anti-depressants, stimulants and antipsychotics), with many of them being on anti-epileptic medication simultaneously. Despite this high level of psychotropic use, few studies exist investigating the pharmacokinetics, pharmacodynamics or side-effect profiles in this population. Multiprofessional and parent partnership is essential in managing autism and psychopharmacology should be used in conjunction with environmental manipulation, educational modification and/or behavioral management strategies. A symptomatic approach to managing the difficult behaviours associated with autism is recommended. Some symptoms of autism may be medication responsive (hyperactivity, obsessions, rituals, inattention, tics, etc), while other symptoms may be responsive to behavioural interventions, but may require medication (aggression, anxiety, depression, impulsivity, sleep difficulties, etc), and symptoms which need specific skill remediation are usually non-responsive to medication (deficits in academic, social or sport domains). The new atypical antipsychotics (such as risperidone, olanzapine, amisulpiride, quetiapine) and SSRIs are increasingly being used in autism, with encouraging results, but a risk-benefit ratio of pharmacotherapy is essential with due weight being given to the side-effects of medication. Despite symptomatic improvement with medication, one should remain cautious about long-term use of psychotropics. It is also important to recognize that psychotropics can sometimes worsen behaviour, and can produce iatrogenic symptoms. Certain anti-epileptic medication and psychotropic drugs are metabolized by the same cytochrome P450 isoenzymes in the liver. In such circumstances, the addition of a psychotropic agent may drastically alter the levels of the anti-epileptic medication and vice versa. It is suggested that specialist clinics should be involved when one is considering complex medication regimes, experimental drugs, polypharmacy, or if patients show unusual side-effects or is drug resistant.
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PMID:Pharmacotherapy of target symptoms in autistic spectrum disorders. 1140 59

After a functional analysis indicated that aggression of an 8-year-old boy with autism was maintained by access to preferred items, antecedent manipulations involving the relative preference of restricted and noncontingently available stimuli were conducted. Restricting highly preferred items evoked the highest rates of aggression regardless of the preference level of the noncontingently available alternative items. Restricting less preferred stimuli was associated with moderate rates of aggression even when the alternative items were more preferred.
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PMID:Antecedent manipulations in a tangible condition: effects of stimulus preference on aggression. 1142 19

Atypical antipsychotic medications for self-injurious behavior (SIB), aggression, and destruction among people with mental retardation and development disabilities are becoming increasingly accepted. Most studies are on risperidone and fewer have been conducted on clozapine. The present single-blind study reports marked reductions in SIB and aggression of two persons with profound mental retardation who were nonresponsive to all other behavioral and psychopharmacological interventions, including risperidone. The most effective dose was 200 mg/day. Side effects were mild and the drug was tolerated well.
J Autism Dev Disord 2001 Feb
PMID:Brief report: effects of clozapine on self-injurious behavior of two risperidone nonresponders with mental retardation. 1143 49

Many persons who have developmental disabilities and challenging behaviors are treated with multiple medications combined with nonpharmacological approaches. However, the comparative effects from pharmacotherapy frequently are not assessed empirically, do not include corollary behavioral measures, and are not evaluated in the long term. The present single-case study incorporated behavioral assessment methodology in an "open label" evaluation of anticonvulsant (clonazepam), beta-blocking (propanolol), and antidepressant (sertraline and clomipramine) medications on severe aggression in a child with autism. Clinically significant reductions in aggressive behavior were attained with the administration of clomipramine and the reductive effects from the medication persisted for 1.7 years. In addition, clomipramine was associated with the elimination of crisis intervention procedures that had been required to manage the child's aggression. These findings add to the clinical literature describing effective treatment of serious behavior disorders in persons with developmental disabilities using antidepressant medication.
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PMID:Pharmacotherapy for severe aggression in a child with autism: "open label" evaluation of multiple medications on response frequency and intensity of behavioral intervention. 1149 58

Low serotonin activity in man has been related to impulsive, self-destructive violence but not to instrumental aggression aimed at dominance. A relationship has also been suggested between aggression and high catecholaminergic activity. Several studies have reported signs of aberrant dopaminergic function in attention deficit hyperactivity disorder, autism, and schizophrenia. In 22 violent offenders undergoing pretrial forensic psychiatric investigation, interpersonal and behavioral features of psychopathy, measured by the Psychopathy Checklist Revised (PCL-R), were significantly predicted by low cerebrospinal fluid (CSF) concentrations of 5-HIAA and high CSF concentrations of HVA in multivariate regression models. CSF concentrations of MHPG did not contribute to the model. This seems to link the outward-directed aggression of psychopathy to serotonergic hypofunctioning and high dopamine turnover, which might account for disinhibition of destructive impulses.
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PMID:CSF studies in violent offenders. I. 5-HIAA as a negative and HVA as a positive predictor of psychopathy. 1151 52


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