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PubMed1992

Clonidine treatment of hyperactive and impulsive children with autistic disorder.

Many autistic children have associated problems of inattention, impulsivity, and hyperactivity that limit the effectiveness of educational and behavioral interventions. Few controlled psychopharmacologic trials have been conducted in autistic children to determine which agents may be effective for these associated features. Eight male children (8.1 +/- 2.8 years) with autistic disorder, diagnosed by DSM-III-R criteria, completed a placebo-controlled, double-blind crossover trial of clonidine. Subjects were included in the study if they had inattention, impulsivity, and hyperactivity that was excessive for their developmental level. Subjects had not tolerated or responded to other psychopharmacologic treatments (neuroleptics, methylphenidate, or desipramine). Teacher ratings on the Aberrant Behavior Checklist irritability, stereotypy, hyperactivity, and inappropriate speech factors were lower during treatment with clonidine than during treatment with placebo. Attention deficit disorder with hyperactivity: Comprehensive Teacher's Rating Scale ratings were not significantly improved during the study, except for oppositional behavior. Parent Conners Abbreviated Parent-Teacher Questionnaire ratings significantly improved during clonidine treatment. Clonidine led to increased ratings of the side effects of drowsiness and decreased activity. Clinician ratings (Children's Psychiatric Rating Scale Autism, Hyperactivity, Anger and Speech Deviance factors; Children's Global Assessment Scale; Clinical Global Impressions efficacy) of videotaped sessions were not significantly different between clonidine and placebo. Clonidine was modestly effective in the short-term treatment of irritability and hyperactivity in some children with autistic disorder.

Ambulatory Care↗
PubMedDate not supplied

Drug therapy for attention-deficit/hyperactivity disorder-like symptoms in autistic disorder.

Problems of inattention and hyperactivity affect one half of individuals with autistic disorder. Care must be taken to ensure that inattention and hyperactivity are not manifestations of other behavioural pathology seen in association with autistic disorder, as this will affect treatment decisions. The prescribing of psychotropic agents to individuals with autistic disorder is increasing but the evidence base is limited, with some exceptions, to uncontrolled studies. Substantial benefit in reducing inattention and hyperactivity is seen with atypical antipsychotics such as risperidone and quetiapine, although weight gain and sedation are common side effects. Moderate benefit is derived from methylphenidate, atomoxetine, some anticonvulsant medications, guanfacine and donepezil. Data show dexamphetamine, clonidine, clomipramine, mirtazapine, and fluoxetine are of unlikely benefit.

Adolescent↗
PubMed2003

Identification of MeCP2 mutations in a series of females with autistic disorder.

Rett disorder and autistic disorder are both pervasive developmental disorders. Recent studies indicate that at least 80% of Rett Disorder cases are caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. Since there is some phenotypic overlap between autistic disorder and Rett disorder, we analyzed 69 females clinically diagnosed with autistic disorder for the presence of mutations in the MeCP2 gene. Two autistic disorder females were found to have de novo mutations in the MeCP2 gene. These data provide additional evidence of variable expression in the Rett disorder phenotype and suggest MeCP2 testing may be warranted for females presenting with autistic disorder.

Adolescent↗
PubMed2004

External validity of childhood disintegrative disorder in comparison with autistic disorder.

To examine the external validity of DSM-IV childhood disintegrative disorder (CDD), 10 children (M = 8.2 yrs) with CDD and 152 gender- and age-matched children with autistic disorder (AD) were compared on 24 variables. The CDD children had a significantly higher rate of epilepsy, significantly less uneven intellectual functioning, and a tendency of greater abnormality in auditory responsiveness than AD children, to validate CDD externally. Their short-term outcome, as shown in the degree of retardation, was not worse than the AD children, which is in disagreement with previous studies reporting worse outcomes in CDD than autism. These results need to be verified by a long-term prospective study that compares CDD and AD patients from infancy.

Autistic Disorder↗
PubMed2004

Associated medical disorders and disabilities in children with autistic disorder: a population-based study.

A population-based survey was conducted among 152,732 Finnish children and adolescents aged under 16 years and living in northern Finland. Diagnoses and associated medical conditions were derived from the hospital and institutional records of this area. One hundred and eighty-seven children with DSM-IV autistic disorder were identified. Associated medical disorders or associated disorders of known or suspected genetic origin were found in 12.3 percent, including tuberous sclerosis, Down syndrome, fragile X syndrome, Klinefelter syndrome, XYY syndrome, chromosome 17 deletion, chromosome 46, XX, dup(8) (p) and mitochondriopathy. Other associated medical disorders identified were epilepsy, hydrocephalus, foetal alcohol syndrome and cerebral palsy. Hearing impairments were found in 8.6 percent and severe impairment of vision in 3.7 percent of the individuals with autistic disorder. Medical disorders seem to have a special impact on the genesis of autistic disorder and need to be thoroughly examined in each child with autistic disorder.

Adolescent↗
PubMed2001

Full-genome scans with autistic disorder: a review.

Autistic disorder is characterized by severe disturbances of social relatedness, impairments in language and communication, and restricted, repetitive, and stereotyped patterns of behaviors. Accumulated data strongly support the notion that genetic factors, as yet undetermined, play a significant role in the etiology of this syndrome. As genetic research in autism is still exploratory, full genomewide searches have been performed to localize susceptibility regions within the genome. Methods and results from the four first full-genome scans published to date (IMGSAC, 1998a; Philippe et al., 1999; Risch et al., 1999d; Barrett et al., 1999) are considered in this review. The four sets of multipoint linkage results are grouped in a single figure to facilitate comparisons among the four studies and with previous or future results. Although findings must be considered with caution because LOD score values do not reach the threshold for significant linkage, a region of approximately 50 cM on the long arm of chromosome 7 appears to play a role in the etiology of autistic disorder.

Adult↗
PubMed2003

Tianeptine: a novel strategy of psychopharmacological treatment of children with autistic disorder.

OBJECTIVES: Many autistic children have problems of eye contact and expressive language that limit the effectiveness of educational and behavioural interventions. Few controlled psychopharmacological trials have been conducted in autistic children to determine which agents may be effective for these associated features. METHODS: Twelve male children (7.3 +/- 3.3 years) with autistic disorder, diagnosed by ICD-10 criteria, completed a placebo-controlled, double-blind crossover trial of tianeptine, which lasted for 12 weeks. Subjects were included in the study if their eye contact and expressive language was inadaequate for their developmental level. Subjects had not tolerated or responded to other psychopharmacological treatments (neuroleptics, methylphenidate, clonidine or desipramine). RESULTS: Teacher ratings on the aberrant behaviour checklist irritability, stereotypy and inappropriate speech factors were lower during treatment with tianeptine than during treatment with placebo. Clinician ratings (children's psychiatric rating scale autism, anger and speech deviance factors; children's global assessment scale; clinical global impressions efficacy) of videotaped sessions were not significantly different between tianeptine and placebo. DISCUSSION: Tianeptine were modestly effective in the short-term treatment of irritability in some children with autistic disorder.

Adolescent↗
PubMed1998

Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers.

Autistic disorder is a complex genetic disease. Because of previous reports of individuals with autistic disorder with duplications of the Prader-Willi/Angelman syndrome critical region, we screened several markers across the 15q11-13 region, for linkage disequilibrium. One hundred forty families, consisting predominantly of a child with autistic disorder and both parents, were studied. Genotyping was performed by use of multiplex PCR and capillary electrophoresis. Two children were identified who had interstitial chromosome 15 duplications and were excluded from further linkage-disequilibrium analysis. Use of the multiallelic transmission-disequilibrium test (MTDT), for nine loci on 15q11-13, revealed linkage disequilibrium between autistic disorder and a marker in the gamma-aminobutyric acidA receptor subunit gene, GABRB3 155CA-2 (MTDT 28.63, 10 df, P=.0014). No evidence was found for parent-of-origin effects on allelic transmission. The convergence of GABRB3 as a positional and functional candidate along with the linkage-disequilibrium data suggests the need for further investigation of the role of GABRB3 or adjacent genes in autistic disorder.

Autistic Disorder↗
PubMedDate not supplied

The pharmacotherapy of target symptoms associated with autistic disorder and other pervasive developmental disorders.

Research into the pharmacotherapy of autistic disorder has steadily increased over the past two decades. Several psychoactive medications have shown efficacy for selected symptoms of autistic disorder and can be used to augment critical educational and behavioral interventions that are the mainstays of treatment. A comprehensive review of medication trials conducted in individuals with autistic disorder and other pervasive developmental disorders is presented. The typical antipsychotic haloperidol is the best-studied medication in autistic disorder but is associated with a high rate of dyskinesias. Investigations to date suggest that the atypical antipsychotics such as risperidone have efficacy for certain symptoms of autistic disorder and may be better tolerated than typical antipsychotics. Preliminary results from trials with serotonin-reuptake inhibitors are favorable, although efficacy has not been demonstrated in younger age groups. Recent controlled studies of nalfrexone suggest that the drug has minimal efficacy. In two small controlled investigations, clonidine was more effective than placebo for a variety of symptoms, including hyperactivity and irritability; in one of these studies, however, the majority of patients relapsed within several months. Psychostimulants reduced hyperactivity and irritability in one small double-blind crossover study in children with autistic disorder, although these agents are frequently reported to exacerbate irritability, insomnia, and aggression in clinical populations. Recent controlled trials of secretin have not shown efficacy compared to placebo. Several other medications, including buspirone, mood stabilizers, and beta-blockers, have produced symptom reduction in some open-label studies and may warrant controlled investigation.

Adrenergic Antagonists↗
PubMed2004

Cyproheptadine in the treatment of autistic disorder: a double-blind placebo-controlled trial.

OBJECTIVE: Autism is a childhood-onset disorder of unknown, possibly of multiple aetiologies. The core symptoms of autism are abnormalities in social interaction, communication and behaviour. The involvement of neurotransmitters such as 5-HT has been suggested in neuropsychiatric disorders and particularly in autistic disorder. Increased platelet 5-HT levels were found in 40% of the autistic population, suggesting that hyperserotonaemia may be a pathologic factor in infantile autism. Therefore, it is of interest to assess the efficacy of cyproheptadine, a 5-HT2 antagonist in the treatment of autistic disorder. In this 8-week double-blind, placebo-controlled trial, we assessed the effects of cyproheptadine plus haloperidol in the treatment of autistic disorder. METHODS: Children between the ages 3 and 11 years (inclusive) with a DSM IV clinical diagnosis of autism and who were outpatients from a specialty clinic for children at Roozbeh Psychiatric Teaching Hospital were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to cyproheptadine + haloperidol (Group A) or haloperidol + placebo (Group B) for an 8-week, double-blind, placebo-controlled study. The dose of haloperidol and cyproheptadine was titrated up to 0.05 and 0.2 mg/kg/day respectively. Patients were assessed by a third-year resident of psychiatry at baseline and after 2, 4, 6 and 8 weeks of starting medication. The primary measure of the outcome was the Aberrant Behaviour Checklist-Community (ABC-C) and the secondary measure of the outcome was the Childhood Autism Rating Scale (relating to people and verbal communication). Side effects and extrapyramidal symptoms were systematically recorded throughout the study and were assessed using a checklist and the Extrapyramidal Symptoms Rating Scale, administered by a resident of psychiatry during weeks 1, 2, 4, 6 and 8. RESULTS: The ABC-C and the Childhood Autism Rating Scale scores improved with cyproheptadine. The behaviour of the two treatments was not homogeneous across time (groups-by-time interaction, Greenhouse-Geisser correction; F = 7.30, d.f. = 1.68, P = 0.002; F = 8.21, d.f. = 1.19, P = 0.004 respectively). The difference between the two treatments was significant as indicated by the effect of group, and the between-subjects factor (F = 4.17, d.f. = 1, P = 0.048; F = 4.29, d.f. = 1, P = 0.045 respectively). No significant difference was observed between the two groups in terms of extrapyramidal symptoms (P = 0.23). The difference between the two groups in the frequency of side effects was not significant. CONCLUSION: The results suggest that the combination of cyproheptadine with a conventional antipsychotic may be superior to conventional antipsychotic alone for children with autistic disorder. However the results need confirmation by a larger randomized controlled trial.

Autistic Disorder↗
PubMed2005

Nocturnal excretion of 6-sulphatoxymelatonin in children and adolescents with autistic disorder.

BACKGROUND: Many studies in autistic disorder report sleep problems and altered circadian rhythms, suggesting abnormalities in melatonin physiology. Additionally, melatonin, a pineal gland hormone produced from serotonin, is of special interest in autistic disorder given reported alterations in central and peripheral serotonin neurobiology. METHODS: Nocturnal urinary excretion of 6-sulphatoxymelatonin was measured by radioimmunoassay in groups of children and adolescents with autistic disorder (n = 49) and normal control individuals (n = 88) matched on age, sex, and Tanner stage of puberty. RESULTS: Nocturnal 6-sulphatoxymelatonin excretion rate was significantly and substantially lower in patients with autism than in normal controls (mean +/- SEM, .75 +/- .11 vs. 1.80 +/- .17 microg/hr, p =.0001), and was significantly negatively correlated with severity of autistic impairments in verbal communication and play (p < .05). CONCLUSIONS: These findings indicate clearly that nocturnal production of melatonin is reduced in autism. Further research is warranted in order to understand the mechanisms underlying the lower melatonin production, to assess the impact of altered melatonin on the pathophysiology and behavioral expression of autistic disorder, and to determine the utility of melatonin administration in individuals with autism.

Adolescent↗
PubMed2005

Epidemiology of autistic disorder and other pervasive developmental disorders.

Is the incidence of autistic disorder and other pervasive developmental disorders (PDDs) increasing? Recent epidemiological surveys of autistic disorder and other PDDs have heightened awareness of and concern about the prevalence of these disorders; however, differences in survey methodology, particularly changes in case definition and case identification over time, have made comparisons between surveys difficult to perform and interpret. Recent surveys suggest that the rate of all PDDs is about 60 per 10,000. The prevalence of autism today is estimated at 13 per 10,000, Asperger's disorder is approximately 3 per 10,000, and childhood disintegrative disorder is very rare at about 0.2 per 10,000. The assessment process, sample size, publication year, and geographic location of studies all have an effect on prevalence estimates. In addition, data from many of these surveys indicate correlates of autistic disorder and other PDDs with IQ, gender, and other medical disorders.

Adolescent↗
PubMed2006

Exploratory and confirmatory factor analyses of the pervasive developmental disorders rating scale for young children with autistic disorder.

In this study, the authors examined the construct validity of the Pervasive Developmental Disorder Rating Scale (PDDRS; R. C. Eaves, 1993), which is a screening instrument used to identify individuals with autistic disorder and other pervasive developmental disorders. The PDDRS is purported to measure 3 factors--arousal, affect, and cognition-that collectively make up the construct of autism. Using scores from 199 children (aged 1-6 years) diagnosed with autistic disorder, the authors submitted data to exploratory and confirmatory factor analyses. In the 1st series of analyses, the authors analyzed a user-specified 3-factor solution using principal axis factor analysis with a promax rotation to evaluate the assertion of a correlated 3-factor structure. Next, the authors analyzed 1-factor and 2-factor solutions to determine if they provided a better factor structure for the data. In the 2nd series, the authors conducted confirmatory factor analyses, which compared the theorized hierarchical 2nd-order factor model with 5 plausible competing models. The results of the exploratory analyses supported the 3-factor solution. With the confirmatory analyses, the 2nd-order factor model provided the best fit for the data. The exploratory and confirmatory analyses supported the theoretical assumptions undergirding the development of the PDDRS. The authors discuss theoretical implications, practical implications, and areas for further research.

Affect↗
PubMed2002

Autistic disorder and gastrointestinal disease.

Autistic disorder is a pervasive developmental disorder manifested in the first 3 years of life by dysfunction in social interaction and communication. Many efforts have been made to explore the biologic basis of this disorder, but the etiology remains unknown. Recent publications describing upper gastrointestinal abnormalities and ileocolitis have focused attention on gastrointestinal function and morphology in these children. High prevalence of histologic abnormalities in the esophagus, stomach, small intestine and colon, and dysfunction of liver conjugation capacity and intestinal permeability were reported. Three surveys conducted in the United States described high prevalence of gastrointestinal symptoms in children with autistic disorder. Treatment of the digestive problems may have positive effects on their behavior.

Age Factors↗
PubMed1995

Use of methylphenidate in the treatment of children with autistic disorder.

The use of psychostimulants in autistic disorder has not received extensive evaluation. Furthermore, their use for the symptomatic control of autistic disorder has been felt to be contraindicated. This study investigates the use of methylphenidate (MPH) for the treatment of selected symptoms of autistic disorder. Ten children, ages 7-11, with a DSM-III-R diagnosis of autistic disorder participated in a double-blind crossover study using placebo and two MPH doses (10 mg or 20 mg bid). Subjects showed modest but statistically significant improvement on MPH over placebo. No significant side effects including worsening stereotypic movements occurred on either dose. Improvement in hyperactivity and lack of adverse effects suggest that MPH may be useful in the treatment of hyperactive autistic children.

Autistic Disorder↗
PubMed1989

Chromosome findings in twins with early-onset autistic disorder.

In a twin study of autistic disorder, chromosome analyses were carried out in nine pairs of monozygotic (MZ) twins, two pairs of dizygotic (DZ) twins, one set of MZ triplets, one single twin from a MZ pair, and seven single twins from DZ pairs. All but one of the MZ sets were concordant for autistic disorder; all DZ pairs were discordant. Fragile X(q)(27.3) was found in one pair of MZ twins and in MZ triplets, i.e., in 9% of the population with autistic disorder. A marker chromosome of unknown origin was detected in a male twin with autistic disorder from a discordant DZ pair.

Autistic Disorder↗
PubMed1999

Exploring the boundaries of pervasive developmental disorder not otherwise specified: analyses of data from the DSM-IV Autistic Disorder Field Trial.

This study aimed to explore the boundaries between PDD and related disorders and to develop classificatory algorithms for what is currently called Pervasive Developmental Disorder Not Otherwise Specified (PDDNOS). Data collected by means of a standard coding system for the DSM-IV field trial for autistic disorder were used. Information on diagnostic criteria for autistic disorder as listed in ICD-10 and DSM-IV was compared between subjects functioning at least in the mildly retarded range and clinically classified as autistic disorder (n = 205), PDDNOS (n = 80) and other non-PDD disorders (n = 174). Only a limited number of items from the ICD-10 and DSM-IV systems for autistic disorder significantly discriminated the PDDNOS group from other disorders. A scoring rule based on a short set of 7 ICD-10/DSM-IV criteria with a cutoff of 3 items and 1 social interaction item set as mandatory had the best balance between high sensitivity and high specificity in discriminating PDDNOS from non-PDD disorders. These rules yielded a somewhat better prediction than most effective rules based on the full set of 12 criteria for autistic disorder with a cutoff of 4 items and 1 social item as mandatory. Generally accepted and well-validated criteria to identify individuals with PDDNOS should facilitate both research and clinical services.

Adolescent↗