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PubMed1993

Haloperidol withdrawal and weight changes in autistic children.

The long-term effects of haloperidol on weight were assessed in 30 children, 25 males and 5 females, diagnosed with autistic disorder whose ages ranged from 3.08 to 8.42 years. They received haloperidol (0.25-3.50 mg/day; mean 1.26 +/- 0.84) for 6 months followed by a 4-week drug withdrawal period. Weights obtained on the last day of the 6-month haloperidol period were compared to weights obtained following drug withdrawal. There was no significant difference between the mean weights obtained on the last day of haloperidol administration (24.799 +/- 9.741 kg) compared to the mean weights at the end of the fourth week of the placebo period (24.644 +/- 9.833 kg). Weights increased during the first week of drug discontinuation (24.879 +/- 9.855 kg), but decreased during each following week of drug withdrawal. Weight was measured monthly during the 6-month haloperidol treatment period for 8 of the 30 subjects. In this subsample, weight gain was greater during the 1-month period lasting from the end of the 4-week drug withdrawal to the end of the first month after resuming haloperidol treatment than weight gain prior to drug withdrawal, between the fifth and sixth month of haloperidol treatment.

Autistic Disorder↗

PubMed1995

Naltrexone in young autistic children: a double-blind, placebo-controlled crossover study.

OBJECTIVE: This study evaluated the efficacy and safety of naltrexone, an opiate blocker, in the treatment of autism. METHOD: Thirteen children with autistic disorder, aged 3.4 to 8.3 years (mean 5.4), were studied in home, school, and outpatient laboratory. Naltrexone, 1.0 mg/kg, was given daily in a randomized, double-blind, placebo-controlled crossover design. Dependent measures included parent and teacher Clinical Global Impressions (CGI), Conners Rating Scales, and Naltrexone Side-Effects (SE) Rating Scale; laboratory CGI, movement actometer readings, and a 10-second interval recording system analysis of on-task, communication initiations, disruptive behavior, and self-stimulation. RESULTS: Eight of 13 subjects improved in two or more settings. Changes in parent measures (CGI, Conners Impulsivity-Hyperactivity Factor, and SE-Restlessness) and Teacher CGI achieved statistical significance. Teacher SE-Restlessness and initiation of communication in the clinic showed a trend toward improvement. Actometer readings improved in two children who were very active at baseline. Adverse side effects were behavioral, mild, and transient. Administering the bitter tablet was a challenge. CONCLUSIONS: Naltrexone offers promise as an agent for modest improvement of behavior and social communication in young children with autism. Parent and teacher measures can be useful in outpatient trials to evaluate change.

Autistic Disorder↗

PubMed2004

[Sixty years of autism].

The concept of autism has been broadened the last few years from 'early infantile autism' to 'an autistic spectrum'. Autism and related contact disorders are grouped together under 'pervasive developmental disorders' or 'autistic spectrum disorders'. The autistic disorder, Asperger's syndrome, pervasive developmental disorder not otherwise specified (PDD-NOS), Rett's disorder and the childhood disintegrative disorder all belong to this group. People with an autistic spectrum disorder have severe difficulties in the integration of perceived stimuli into a meaningful entity. More than two-thirds of the people with the autistic disorder (classical autism) are also mentally retarded. Although autism can still only be diagnosed at the behavioural level, there is considerable consensus regarding an underlying organic aetiology. Autism is clearly a multifactorial condition. Autism cannot be cured, but adequate intervention can significantly improve the quality of life of people with this disorder. Diagnosis and intervention are highly interrelated. In the intervention, a distinction is made between family-oriented and child-oriented strategies. Augmentative communication plays a key role in the treatment. People with autism need a lot of structure, clarity and predictability, also when they have become adults.

Adolescent↗

PubMed2002

Race differences in the age at diagnosis among medicaid-eligible children with autism.

OBJECTIVE: To examine racial differences in the age at which Medicaid-eligible children first receive an autistic disorder (AD) diagnosis and to examine time in mental health treatment until an AD diagnosis was received. METHOD: Philadelphia Medicaid specialty mental health claims identified 406 children who received services in 1999 for AD. Claims from 1993-1999 were used to identify the date of first mental health visit, first receipt of AD diagnosis, and number of visits occurring between those dates. Linear regression was used to examine the relationship among race, age at first diagnosis of AD, time in mental health treatment, and number of visits until the diagnosis was made. RESULTS: On average, white children received the AD diagnosis at 6.3 years of age, compared with 7.9 years for black children (p <.001). White children entered the mental health system at an earlier age (6.0 versus 7.1 years, p =.005); however, after adjusting for age, sex, and time eligible for Medicaid, black children required more time in treatment before receiving the diagnosis. CONCLUSIONS: Important disparities exist in the early detection and treatment of autism. These disparities may be the result of differences in help-seeking, advocacy and support, and clinician behaviors.

Black or African American↗

PubMed1997

Autism or atypical autism in maternally but not paternally derived proximal 15q duplication.

Duplications of proximal 15q have been found in individuals with autistic disorder (AD) and varying degrees of mental retardation. Often these abnormalities take the form of a supernumerary inverted duplicated chromosome 15, more properly described as an isodicentric chromosome 15, or idic(15). However, intrachromosomal duplications also have been reported. In a few cases, unaffected mothers, as well as their affected children, carry the same duplications. During the course of the genotyping of trios of affected probands with AD and their parents, at the positional candidate locus D15S122, an intrachromosomal duplication of proximal 15q was detected by microsatellite analysis in a phenotypically normal mother. Microsatellite and methylation analyses of the pedigree in the following report show that, among three children, the two with autism or atypical autism have maternal inheritance of a 15q11-q13 duplication whereas the third child, who is unaffected, did not inherit this duplication. Their mother's 15q11-q13 duplication arose de novo from her father's chromosomes 15. This finding documents, for the first time, the significance of parental origin for duplications of 15q11-q13. In this family, paternal inheritance leads to a normal phenotype, and maternal inheritance leads to autism or atypical autism.

Aneuploidy↗

PubMed2001

Linkage disequilibrium at the Angelman syndrome gene UBE3A in autism families.

Autistic disorder is a neurodevelopmental disorder with a complex genetic etiology. Observations of maternal duplications affecting chromosome 15q11-q13 in patients with autism and evidence for linkage and linkage disequilibrium to markers in this region in chromosomally normal autism families indicate the existence of a susceptibility locus. We have screened the families of the Collaborative Linkage Study of Autism for several markers spanning a candidate region covering approximately 2 Mb and including the Angelman syndrome gene (UBE3A) and a cluster of gamma-aminobutyric acid (GABA(A)) receptor subunit genes (GABRB3, GABRA5, and GABRG3). We found significant evidence for linkage disequilibrium at marker D15S122, located at the 5' end of UBE3A. This is the first report, to our knowledge, of linkage disequilibrium at UBE3A in autism families. Characterization of null alleles detected at D15S822 in the course of genetic studies of this region showed a small (approximately 5-kb) genomic deletion, which was present at somewhat higher frequencies in autism families than in controls.

Alleles↗

PubMed1996

Clinical characteristics of children referred to a child development center for evaluation of speech, language, and communication disorders.

Speech, language, and communication disorders are prominent reasons for referrals to a child development center. From 1984 to 1988, 1,090 preschool children were referred to our child development center, which serves the Tel Aviv metropolitan area. Of all referrals, 432 (41%) were primarily due to speech, language, and communication problems. After exclusion of those with IQ < 50 and those with non-language-related disabilities, 323 children remained. The children were classified into different subtypes of developmental language disorders and autistic spectrum disorders. The main developmental language disorder subtypes were combined expressive-receptive (49%) and expressive (44%). Central processing deficits were less common, occurring in 20 (7%) of the children. Parents of children with developmental language disorders had educational levels similar to those of parents of children referred to the child development center for other causes. However, parents of children with infantile autism had higher educational levels than parents of children with developmental language disorder or parents of children referred for other causes (P < .001). Our results reflect the distribution of language and related problems in an unselected population of preschool children referred to a child development center.

Autistic Disorder↗

PubMed2006

Parent satisfaction in a multi-site acute trial of risperidone in children with autism: a social validity study.

RATIONALE: Subjects who view experimental procedures as worthwhile are more likely to participate in clinical trials and comply with study procedures. Designing studies that consider the consumer's perspective will help to forge a better alliance between participants and researchers. OBJECTIVE: Participant satisfaction is seldom assessed in pharmacological research. In this paper, we report on parent satisfaction in a randomized clinical trial in children with autistic disorder and severely disruptive behavior. METHOD: Parents of 101 children with autism who had participated in a multi-site 8-week double-blind clinical trial of risperidone were given a questionnaire at the end to elicit their perceptions of the appropriateness and acceptability of clinical trial procedures. RESULTS: Ninety-six (95.0%) parents returned the questionnaire. Of these, 80.0 to 96.8%, depending on the question, expressed satisfaction with their child's research participation regardless of treatment outcome or assignment to active drug or placebo. In all, 90.5% of parents indicated that they would "definitely" recommend the clinical trial to other families with similar children. A total of 92.7% indicated that they would rejoin the clinical trial if they had to do it all over again. Ethnic minority subjects were more satisfied than white participants with the use of "learning tests". CONCLUSIONS: Parents of children participating in this trial were highly satisfied and supportive of the clinical trial procedures. Random assignment to drug or placebo and the clinical response of their children did not appear to influence their views. Further satisfaction studies of this sort are encouraged.

Adolescent↗

PubMed2006

Regional gray matter volumetric changes in autism associated with social and repetitive behavior symptoms.

BACKGROUND: Although differences in brain anatomy in autism have been difficult to replicate using manual tracing methods, automated whole brain analyses have begun to find consistent differences in regions of the brain associated with the social cognitive processes that are often impaired in autism. We attempted to replicate these whole brain studies and to correlate regional volume changes with several autism symptom measures. METHODS: We performed MRI scans on 24 individuals diagnosed with DSM-IV autistic disorder and compared those to scans from 23 healthy comparison subjects matched on age. All participants were male. Whole brain, voxel-wise analyses of regional gray matter volume were conducted using voxel-based morphometry (VBM). RESULTS: Controlling for age and total gray matter volume, the volumes of the medial frontal gyri, left pre-central gyrus, right post-central gyrus, right fusiform gyrus, caudate nuclei and the left hippocampus were larger in the autism group relative to controls. Regions exhibiting smaller volumes in the autism group were observed exclusively in the cerebellum. Significant partial correlations were found between the volumes of the caudate nuclei, multiple frontal and temporal regions, the cerebellum and a measure of repetitive behaviors, controlling for total gray matter volume. Social and communication deficits in autism were also associated with caudate, cerebellar, and precuneus volumes, as well as with frontal and temporal lobe regional volumes. CONCLUSION: Gray matter enlargement was observed in areas that have been functionally identified as important in social-cognitive processes, such as the medial frontal gyri, sensorimotor cortex and middle temporal gyrus. Additionally, we have shown that VBM is sensitive to associations between social and repetitive behaviors and regional brain volumes in autism.

Adolescent↗

PubMed2003

The neurobiological context of autism.

Autistic disorder (AD) is a complex neuropsychiatric disorder of neurodevelopmental origin, where multiple genetic and environmental factors may interact, resulting in a clinical continuum. The genetic component is best described by a multilocus model that takes into account epistatic interactions between several susceptibility genes. In the past ten years enormous progress has been made in identifying chromosomal regions in linkage with AD, but moving from chromosomal regions to candidate genes has proven to be tremendously difficult. Neuroanatomical findings point to early dysgenetic events taking place in the cerebral cortex, cerebellum, and brainstem. At the cellular level, disease mechanisms may include altered cell migration, increased cell proliferation, decreased cell death, or altered synapse elimination. Neurochemical findings in AD point to involvement of multiple neurotransmitter systems. The serotoninergic system has been intensively investigated in AD, but other neurotransmitter systems (e.g., the GABAergic and the cholinergic system) are also coming under closer scrutiny. The role of environmental factors is still poorly characterized. It is not clear yet whether environmental factors act merely as precipitating agents, always requiring an underlying genetic liability, or whether they represent an essential component of a pathogenetic process where genetic liability alone does not lead to the full-blown autism phenotype. A third potential player in the pathogenesis of autism, in addition to genetic and environmental factors, is developmental variability due to "random" factors, e.g. small fluctuations of gene expression and complex, non-deterministic interactions between genes during brain development. These considerations suggest that a non-deterministic conceptual framework is highly appropriate for autism research.

Animals↗

PubMed2003

Behavioral comparisons in autistic individuals from multiplex and singleton families.

Autistic disorder (AD) is a complex neurodevelopmental disorder. The role of genetics in AD etiology is well established, and it is postulated that anywhere from 2 to 10 genes could be involved. As part of a larger study to identify these genetic effects we have ascertained a series of AD families: Sporadic (SP, 1 known AD case per family and no known history of AD) and multiplex (MP, > or = 2 cases per family). The underlying etiology of both family types is unknown. It is possible that MP families may constitute a unique subset of families in which the disease phenotype is more likely due to genetic factors. Clinical differences between the two family types could represent underlying genetic heterogeneity. We examined ADI-R data for 69 probands from MP families and 88 from SP families in order to compare and contrast the clinical phenotypes for each group as a function of verbal versus nonverbal status. Multivariate analysis controlling for covariates of age at examination, gender, and race (MANCOVA) revealed no differences between either the verbal or nonverbal MP and SP groups for the three ADI-R area scores: social interaction, communication, and restricted/repetitive interests or behaviors. These data failed to find clinical heterogeneity between MP and SP family types. This supports previous work that indicated that autism features are not useful as tools to index genetic heterogeneity. Thus, although there may be different underlying etiologic mechanisms in the SP and MP probands, there are no distinct behavioral patterns associated with probands from MP families versus SP families. These results suggests the possibility that common etiologic mechanisms, either genetic and/or environmental, could underlie all of AD.

Autistic Disorder↗

PubMed2005

Acute and long-term safety and tolerability of risperidone in children with autism.

Treatment-emergent adverse events (AEs) were monitored during an 8-week, double-blind, placebo-controlled trial of risperidone (0.5-3.5 mg/day) in 101 children and adolescents with a lifetime diagnosis of autistic disorder. In addition, 37 placebo nonresponders received open-label risperidone for another 8 weeks. Of all the risperidone responders (n=65), 63 entered an open extension of another 16 weeks (6 months total risperidone exposure), and 32 of them were rerandomized to either continued risperidone therapy (n=16) or gradual replacement with placebo (n=16) over 8 weeks. We collected the following measures of safety and tolerability: (1) laboratory blood assessments (CBC with differential, electrolytes, and liver function tests) and urinalyses, (2) vital signs, (3) Side Effects Review of AEs thought to be associated with risperidone, (4) sleep records, (5) Simpson Angus Neurological Rating Scale (SARS), (6) Abnormal Involuntary Movement Scale (AIMS), and (7) height and weight. No clinically significant changes were found on the lab tests. During the 8-week acute trial, the most common AEs on the Side Effects Review, scored as moderate or higher, were as follows (placebo and risperidone, respectively): Somnolence (12% and 37%), enuresis (29% and 33%), excessive appetite (10% and 33%), rhinitis (8% and 16%), difficulty waking (8% and 12%), and constipation (12% and 10%). "Difficulty falling asleep" and anxiety actually favored the risperidone condition at statistically significant levels. The same AEs tended to recur through 6 months of treatment, although often at reduced levels. Using Centers for Disease Control (CDC) standardized scores, both weight and body mass index (BMI) increased with risperidone during the acute trial (0.5 and 0.6 SDs, respectively, for risperidone; 0.0 and 0.1 SDs, respectively, for placebo) and into open-label extension (0.19 and 0.16 SDs, respectively), although the amount of gain decelerated with time. Extrapyramidal symptoms, as assessed by the SARS, were no more common for drug than placebo, although drooling was reported more often in the risperidone group. There were no differences between groups on the AIMS. Two subjects had seizures (one taking placebo), but these were considered unrelated to active drug. Most AEs were mild to moderate and failed to interfere with therapeutic changes; there were no unanticipated AEs. The side effects of most concern were somnolence and weight gain.

Adolescent↗

PubMed1992

Validity and reliability of the infant behavioral summarized evaluation (IBSE): a rating scale for the assessment of young children with autism and developmental disorders.

The Infant Behavioral Summarized Evaluation (IBSE) is a rating scale adapted from the Behavioral Summarized Evaluation (BSE) and specifically related to the assessment of behaviors of young children having autistic disorders. Content validity and reliability studies described in the paper were made from behavior ratings of videotapes for 89 children aged from 6 to 48 months. Results show a significant group of 19 items including some characteristic early autistic behaviors (communicative and social abnormalities) and some that are less commonly described in the syndrome (attentional, perceptive, and adaptive disorders). The value of the use of this scale for clinicians and professionals involved in behavioral evaluations and treatment of young children with developmental disorders and the necessity for further psychometric investigations are discussed.

Autistic Disorder↗

PubMedDate not supplied

Use of risperidone in a paediatric population: an observational study.

OBJECTIVE: To evaluate the impact of risperidone on functional impairment in a paediatric sample and to document the range of adverse drug reactions. METHODS: Risperidone treatment in children and adolescents (n = 51) with severe behavioural disturbances was assessed retrospectively to determine clinical response and adverse events. The change in patient functional performance during treatment was assessed using the Royal Alexandra Hospital for Children Measure of Function (MOF) score. Changes in target behaviours (such as severe aggression) were also assessed. RESULTS: The average duration of follow up was 9 months. Clinical improvement was demonstrated in 76% of the sample. There was a statistically significant improvement in the mean MOF with risperidone therapy (10.61 with 99% confidence interval 6.6-14.6). Risperidone appeared to be particularly useful in patients with autistic spectrum disorders. Twenty-five of the 51 patients (49%) experienced side-effects including sedation (27%), weight gain (20%), anticholinergic (10%) and extrapyramidal (8%) side-effects. CONCLUSIONS: This study suggests that risperidone is an effective agent in severely behaviourally disturbed paediatric patients. However, risperidone use is limited by the high frequency of side-effects. Randomized controlled trial data are required to determine the safety and efficacy of risperidone.

Adolescent↗

PubMedDate not supplied

[Communication and speech disorders and their relationship with psychic development and mental disorders in 8 year old children from the Lódź area].

AIM: The aim of the study was to analyze the occurrence of communication and speech disorders among 8-year-old children in Lódź. The comorbidity of these disorders with mental and somatic disorders was also analysed. We have also studied the correlation between the level of language development and the level of psychic development, and the existence and character of mental disorders. METHOD: The study comprised 7881 children from Lódź, born in 1991. The design of the study was two-stage. Stage I consisted of a screening test, using the Questionnaire of Child-Environment Communication Development, which was sent to the parents of all children. On this basis a group of 58 children with communication disorders was identified, which were further evaluated in the stage II of the study. Stage II consisted of a psychiatric examination, Screening Logopedic Test acc.to Tarkowski, Child Developmental Questionnaire acc. to Rabe-Jabłońska and Gmitrowicz, somatic state evaluation and analysis of the available documentation. RESULTS: In 0.81% of the children communication disorders were found. Speech disorders were present in all cases: in 2/3rds expressive language disorders or mixed receptive-expressive language disorders, in the remaining cases phonological disorders. Estimated frequency of occurrence of specific disorders in the studied population was as follows: specific developmental language disorders 2.9/1000, acquired aphasia with epilepsy 4/10000, autistic disorder 6.4/10000. Over one third of children with a verbal communication disorder suffered also from various neurological and developmental disorders; most of the children showed abnormal mental development (f = 0.86) and mental disorders (f = 0.66). CONCLUSIONS: Poor language development correlated statistically significantly with mental retardation, pervasive developmental disorder and behaviour disorders, caused by brain damage or brain dysfunction. Children with a communication disorder who demonstrated normal language development suffered from social maladaptation or ADHD statistically significantly more frequently.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity.

CONTEXT: Hyperactivity and inattention are common symptoms in children with autistic disorder and related pervasive developmental disorders, but studies of stimulants in these conditions have been inconclusive. OBJECTIVES: To determine the efficacy and safety of methylphenidate hydrochloride in children with pervasive developmental disorders and hyperactivity. DESIGN: Double-blind, placebo-controlled, crossover trial followed by open-label continuation. SETTING: Five academic outpatient clinics. PARTICIPANTS: Seventy-two drug-free children, aged 5 to 14 years, with pervasive developmental disorders accompanied by moderate to severe hyperactivity. INTERVENTIONS: Prior to randomization, subjects entered a 1-week test-dose phase in which each subject received placebo for 1 day followed by increasing doses of methylphenidate (low, medium, and high doses) that were each given for 2 days. The low, medium, and high doses of methylphenidate hydrochloride were based on weight, and they ranged from 7.5 mg/d to 50.0 mg/d in divided doses. Subjects who tolerated the test dose (n = 66) were assigned to receive placebo for 1 week and then 3 methylphenidate doses in random order during a double-blind, crossover phase. Children responding to methylphenidate then entered 8 weeks of open-label treatment at the individually determined best dose. MAIN OUTCOME MEASURES: The primary outcome measure was the teacher-rated hyperactivity subscale of the Aberrant Behavior Checklist. Response was defined as "much improved" or "very much improved" on the Clinical Global Impressions Improvement item coupled with considerable reductions in the parent-rated and/or teacher-rated Aberrant Behavior Checklist hyperactivity subscale score. RESULTS: Methylphenidate was superior to placebo on the primary outcome measure, with effect sizes ranging from 0.20 to 0.54 depending on dose and rater. Thirty-five (49%) of 72 enrolled subjects were classified as methylphenidate responders. Adverse effects led to the discontinuation of study medication in 13 (18%) of 72 subjects. CONCLUSIONS: Methylphenidate was often efficacious in treating hyperactivity associated with pervasive developmental disorders, but the magnitude of response was less than that seen in typically developing children with attention-deficit/hyperactivity disorder. Adverse effects were more frequent.

Adolescent↗

PubMed2004

[Attachment in autistic children].

Autistic disorder is a neuropsychiatric disorder which begins in the first years of life with delays and deviance in social, communicative and cognitive development and with restricted repertoire of activities and interests. It is thought that autistic children do not form attachments to parents or caregivers because of their difficulties in social interaction. Yet, the findings of the studies demonstrate evidences for the existence of attachment between autistic children and their caregivers. The aim of the present study is to review the studies that examine the attachment behaviors in autism. Autistic children show similar attachment behaviors when compared to children with normal development, children with other psychiatric disorders, children with Down syndrome and mentally retarded children. Children with autism prefer their mothers to strangers and attempt to remain close to them as much as other children. However they do not engage in attention sharing behaviors such as pointing or showing objects. They also do not seem to recognize the meaning of facial expressions and emotions. Although autism does not exclude the development of secure attachment relationships, it may delay the development of secure attachment and change the behavioral patterns related with attachment security. It is concluded that the awareness of the parents and the clinicians might help to establish treatment alternatives that preserve and improve the attachment behaviors of autistic children.

Adult↗

PubMedDate not supplied

EEG features and epilepsy in patients with autism.

Epileptic seizures are frequently reported (4-32%) in autism. These values are higher than in the normal population of children and adolescents (0.5%). In the literature there is no uniform description of epilepsy in autism. We examined 106 patients with autistic disorder divided into three groups on the basis of presence or absence of EEG paroxysmal abnormalities (PA) and / or epilepsy including febrile convulsions (FG). Our patients presented an autistic syndrome unrelated to clear congenital or acquired encephalopathy. The prevalence of epilepsy and EEG PA was 23.6% and 18.9%, respectively. Significant differences between the three groups appeared for (i) familial antecedents for epilepsy / FC and neurologic and psychiatric diseases (P < 0.004), (ii) a different proportion between the three groups for mental retardation (P < 0.03), (iii) and EEG fast activity (P < 0.04). Our patients showed several types of epilepsy, including idiopathic forms with seizure onset after the age of 10 in 45% of cases. Seizures were mainly partial, not frequent and controllable by anti-epileptic drugs. PA were mostly focal and multifocal and in 45% of cases were typical of benign childhood partial epilepsy with centro-temporal spikes. The higher incidence of epilepsy and EEG PA is apparently not related to organic pre-, peri- and postnatal antecedents or cerebral lesions. On the contrary, genetic factors responsible for autism and epilepsy seem important in the genesis of these two disorders.

Adolescent↗