Effectiveness of N,N-dimethylglycine in autism and pervasive developmental disorder

N,N-dimethylglycine, a dietary supplement, has been reported to be beneficial in children with autism and pervasive developmental disorder. We examined the effectiveness of dimethylglycine in children with autism and pervasive developmental disorder in a double-blind, placebo-controlled study. Thirty-seven children between 3 and 11 years of age with a diagnosis of autism and/or pervasive developmental disorder were gender and age matched and randomly assigned to receive either placebo or dimethylglycine for 4 weeks. All children were assessed before and after treatment on two behavioral measures, the Vineland Maladaptive Behavior Domain and the Aberrant Behavior Checklist. Standardized neurologic examinations before and after treatment on 33 children showed no change. An overall improvement on all behavioral measures was observed for both the placebo and the dimethylglycine groups. However, the improvement among the children who received dimethylglycine was not statistically different from the improvement observed among the children who received the placebo. The children who participated in this study were a heterogeneous group, and their apparent responses to the dimethylglycine varied. Some children appeared to respond positively to the dimethylglycine, and there was a smaller proportion of negative changes in the dimethylglycine group, but the quantitative changes in the dimethylglycine behavioral assessments were not significantly different from what was observed among children who received placebo.     

System and Cost Research Issues in Treatments for People with Autistic Disorders

Parents of children with autism and pervasive developmental disorder and educational and clinical practitioners providing services to them regularly confront a wide range of service selection and financial decisions that are not as yet effectively addressed by applied research. Relevant systems issues span a very broad range of concerns: (a) systems delivery models and issues (e.g., costs of services, implementation of intensive intervention, and teacher or therapist training); (b) how best to integrate treatments; (c) providing treatment to those with limited monetary resources; (d) cost and cost/benefit analyses; (e) how to educate adult psychiatrists (as well as other practitioners and personnel) regarding autism; and (f) gaps between research and practice.     

Autism from 2 to 9 years of age

CONTEXT: Autism represents an unusual pattern of development beginning in the infant and toddler years. OBJECTIVES: To examine the stability of autism spectrum diagnoses made at ages 2 through 9 years and identify features that predicted later diagnosis. DESIGN: Prospective study of diagnostic classifications from standardized instruments including a parent interview (Autism Diagnostic Interview-Revised [ADI-R]), an observational scale (Pre-Linguistic Autism Diagnostic Observation Schedule/Autism Diagnostic Observation Schedule [ADOS]), and independent clinical diagnoses made at ages 2 and 9 years compared with a clinical research team's criterion standard diagnoses. SETTING: Three inception cohorts: consecutive referrals for autism assessment to (1) state-funded community autism centers, (2) a private university autism clinic, and (3) case controls with developmental delay from community clinics. PARTICIPANTS: At 2 years of age, 192 autism referrals and 22 developmentally delayed case controls; 172 children seen at 9 years of age. MAIN OUTCOME MEASURES: Consensus best-estimate diagnoses at 9 years of age. RESULTS: Percentage agreement between best-estimate diagnoses at 2 and 9 years of age was 67, with a weighted kappa of 0.72. Diagnostic change was primarily accounted for by movement from pervasive developmental disorder not otherwise specified to autism. Each measure at age 2 years was strongly prognostic for autism at age 9 years, with odds ratios of 6.6 for parent interview, 6.8 for observation, and 12.8 for clinical judgment. Once verbal IQ (P = .001) was taken into account at age 2 years, the ADI-R repetitive domain (P = .02) and the ADOS social (P = .05) and repetitive domains (P = .005) significantly predicted autism at age 9 years. CONCLUSIONS: Diagnostic stability at age 9 years was very high for autism at age 2 years and less strong for pervasive developmental disorder not otherwise specified. Judgment of experienced clinicians, trained on standard instruments, consistently added to information available from parent interview and standardized observation.     

Two-year outcome of preschool children with autism or Asperger's syndrome

OBJECTIVE: DSM-IV specifies that Asperger's disorder is a type of pervasive developmental disorder without clinically significant cognitive or language delay. There are no data, however, on the outcome of children with Asperger's disorder or on whether their outcome differs from that of children with autism. The objectives of this study were to compare the outcome of groups of children with these disorders over a period of 2 years on variables independent of the defining criteria and to identify variables that might account for these differences. METHOD: All children 4-6 years of age who came for assessment or were currently in treatment at a pervasive developmental disorder service of one of several centers in a large geographic region were identified. Children who received a diagnosis of autism (N=46) or Asperger's syndrome (N=20) on the basis of a diagnostic interview and had an IQ in the nonretarded range were given a battery of cognitive, language, and behavioral tests. Families were contacted roughly 2 years after the date of their enrollment in the study, and many of the tests were readministered. RESULTS: Children with Asperger's syndrome had better social skills and fewer autistic symptoms 2 years after study enrollment than the children with autism. The differences in outcome could not be explained by initial differences in IQ and language abilities. Children with autism who had developed verbal fluency at follow-up were very similar to the children with Asperger's syndrome at study enrollment. CONCLUSIONS: Although the exact mechanism for the differences in outcome remain to be determined, it appears that Asperger's disorder and autism represent parallel but potentially overlapping developmental trajectories.     

Fluvoxamine treatment of a child with severe PDD: a single case study.

Recent reports suggest that selective serotonin reuptake inhibitors (SSRIs) are useful in the treatment of individuals with autism and other pervasive developmental disorders. We report on a single case study of the use of fluvoxamine with a 7-year-old Caucasian girl with severe pervasive developmental disorder. Our findings indicate that fluvoxamine was significantly effective in reducing stereotypical, repetitive behaviors, anxiety, and aggression and in improving prelinguistic and social behaviors. Our results indicate that the use of the SSRIs as a platform for the long-term habilitation of these children should be considered, but further studies are required to establish the efficiency of fluvoxamine for the treatment of children with autism.     

Association of Duchenne muscular dystrophy with autism spectrum disorder

We hypothesize that Duchenne muscular dystrophy and autism spectrum disorder/pervasive developmental disorder co-occur with a greater than random frequency. In this study, we set out to reject the hypothesis that Duchenne muscular dystrophy and autism spectrum disorder/pervasive developmental disorder co-occur no more often than expected by chance. Two index cases and six additional boys with concomitant Duchenne muscular dystrophy and autism spectrum disorder were identified in a muscular dystrophy clinic that approximates the total number of Duchenne muscular dystrophy boys (158) in the state of Massachusetts. The rate of prevalence (6 of 158) was compared with the prevalence rate of autism spectrum disorder in boys in the general population (1.6 in 1,000). We rejected the hypothesis that Duchenne muscular dystrophy and autism spectrum disorder co-occurrence was likely to be explained by chance (P = .006). We identify a previously unrecognized association of Duchenne muscular dystrophy with autism spectrum disorder. Further work might elucidate the level of association between these two conditions, either at the genetic or at the protein level, and might clarify, at least partially, the neurobiologic mechanisms associated with autism spectrum disorder.     

Age of recognition of pervasive developmental disorder

In DSM-III, pervasive developmental disorder is divided into two major categories: infantile autism and childhood onset pervasive developmental disorder. The criteria differ, primarily, in the age of onset. The authors studied 129 patients who had received diagnoses of pervasive developmental disorder or a related disorder and found only five cases of apparent childhood onset pervasive developmental disorder. These five patients were behaviorally indistinguishable from those with other diagnoses. Practically, age of onset may be more appropriately termed "age of recognition," and its use as a major diagnostic criterion for such disorders may not be justified.     

Autistic traits in the general population: a twin study

BACKGROUND: Recent research has indicated that autism is not a discrete disorder and that family members of autistic probands have an increased likelihood of exhibiting autistic symptoms with a wide range of severity, often below the threshold for a diagnosis of an autism spectrum disorder. OBJECTIVE: To examine the distribution and genetic structure of autistic traits in the general population using a newly established quantitative measure of autistic traits, the Social Responsiveness Scale (formerly known as the Social Reciprocity Scale). METHODS: The sample consisted of 788 pairs of twins aged 7 to 15 years, randomly selected from the pool of participants in a large epidemiologic study (the Missouri Twin Study). One parent of each pair of twins completed the Social Responsiveness Scale on each child. The data were subjected to structural equation modeling. RESULTS: Autistic traits as measured by the Social Responsiveness Scale were continuously distributed and moderately to highly heritable. Levels of severity of autistic traits at or above the previously published mean for patients with pervasive developmental disorder not otherwise specified were found in 1.4% of boys and 0.3% of girls. Structural equation modeling revealed no evidence for the existence of sex-specific genetic influences, and suggested specific mechanisms by which females may be relatively protected from vulnerability to autistic traits. CONCLUSIONS: These data indicate that the social deficits characteristic of autism spectrum disorders are common. Given the continuous distribution of these traits, it may be arbitrary where cutoffs are made between research designations of being "affected" vs "unaffected" with a pervasive developmental disorder. The genes influencing autistic traits appear to be the same for boys and girls. Lower prevalence (and severity) of autistic traits in girls may be the result of increased sensitivity to early environmental influences that operate to promote social competency.     

Stereotypy in young children with autism and typically developing children

Although stereotypy is one of the key diagnostic features of autism, few studies have compared stereotypic behavior in children with autism and typically developing children. The present study employed direct observational measurement methods to assess levels of stereotypic behavior in 2-, 3- and 4-year-old children with autism or pervasive developmental disorder - not otherwise specified (PDD-NOS) and age-matched typically developing peers. Thirty children with autism or PDD-NOS and 30 typically developing children participated. Each child's performance of several early learning and play skills was assessed using a direct observational assessment protocol developed for children with autism who were entering early intensive behavioral treatment. Duration of episodes of vocal and motor stereotypy was recorded from a videotaped 10 min portion of that assessment session. Results indicated that the 2-year-old children with autism or PDD-NOS had somewhat higher levels of stereotypic behavior than the typically developing 2-year-olds, while the 3- and 4-year-old children with autism or PDD-NOS displayed substantially higher levels stereotypic behavior than their same-age peers.     

Pervasive developmental disorder and childhood-onset schizophrenia: comorbid disorder or a phenotypic variant of a very early onset illness?

BACKGROUND: Childhood-onset schizophrenia (COS) is a severe form of the adult-onset disorder with a high rate of premorbid developmental abnormalities. Early symptoms of pervasive developmental disorder (PDD) have been reported in five independent studies of COS. In this study, we compared evidence for premorbid PDD as a nonspecific manifestation of impaired neurodevelopment seen in schizophrenia, or as an independent risk factor for COS. METHODS: Diagnosis of past or current autism or PDD was made according to the DSM-IV criteria. COS patients with and without PDD were compared with respect to neuropsychological, clinical, and neurobiological measures. Several candidate genes for autism were examined in the entire COS sample and the subgroup with PDD using the Transmission Disequilibrium Test (TDT) and Quantitative TDT (QTDT). RESULTS: Nineteen (25%) of COS probands had a lifetime diagnosis of PDD: one met criteria for autism, two for Asperger's disorder, and 16 for PDD not otherwise specified. Premorbid social impairment was most common feature for COS-PDD subjects. The PDD group did not differ from the rest of the COS sample with respect to age of onset, IQ, response to medications, and rate of familial schizotypy. Unexpectedly, two siblings of COS-PDD probands met criteria for nuclear autism. There was no difference between PDD and non-PDD groups with respect to initial brain magnetic resonance imaging (MRI) measures. However, rate of gray matter loss was greater for PDD (n = 12) than for the non-PDD (n = 27) subgroup (-19.5 +/- 11.3 mL/year vs. -9.6 +/- 15.3 mL/year; p =.05). None of eight candidate genes for autism were associated with COS or COS-PDD. CONCLUSIONS: Premorbid PDD in COS is more likely to be a nonspecific marker of severe early abnormal neurodevelopment. However, the occurrence of two siblings of COS-PDD probands (17%) with nuclear autism remains to be understood.     

Prevalence of autism in children born to Somali parents living in Sweden: a brief report

In a geographical area of Stockholm, with a relatively large Somali immigrant population, parents as well as teachers in special schools and staff at habilitation centres have raised concerns over whether children with a Somali background are over-represented in the total group of children with autism. The aim of the study was, therefore, to investigate the prevalence of autism in children with parents from Somalia, living in Stockholm county, and to compare the prevalence in children of Somali background with that in the non-Somali group. We reviewed the records of 17 children (13 males, four females), born between 1988 and 1998 (age range 7-17y) and with a Somali background, who had a diagnosis of autistic disorder or pervasive developmental disorder not otherwise specified (PDDNOS) and were registered at either of the two autism habilitation centres for school-aged children. The prevalence of autistic disorder or PDDNOS was found to be three to four times higher than in the non-Somali group (0.7% vs 0.19%). All children also had learning disability.* Our findings warrant further investigations of possible aetiological factors behind the increased prevalence of autistic disorders in children of Somali origin found in this area in Sweden.     

Neuroleptics in pediatric psychiatry.

At the present time, neuroleptics are indicated for the treatment of acute psychotic states as well as Tourette's syndrome in children and adults. Neuroleptics may have a useful role in the attenuation of problem behaviors, such as stereotypies, hyperactivity, self-injury, and aggressive outbursts in infantile autism, pervasive developmental disorder NOS, and mental retardation, but they do not improve the underlying condition. Neuroleptics are not the agents of first choice for treatment of hyperactivity or aggression in children who do not have major developmental handicaps. Common and troublesome side effects associated with neuroleptic use in children and adolescents include sedation, extrapyramidal symptoms, and withdrawal dyskinesias; therefore, close monitoring is required. Neuroleptics should be used cautiously and only as an adjunct to other nonpharmacologic interventions.     

Autism and autistic behavior in Joubert syndrome.

To determine whether individuals with Joubert syndrome exhibit features of autism as defined by the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV), we examined 11 children with Joubert syndrome using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-Generic. Three children met DSM-IV criteria for autistic disorder and one for pervasive developmental disorder not otherwise specified. The other seven all demonstrated at least one DSM-IV symptom of autism, but did not meet criteria for a pervasive developmental disorder. Both total number of DSM-IV symptoms and number of social symptoms distinguished the autism and nonautism subgroups. In contrast, the two subgroups displayed similar levels of communication impairments and repetitive or stereotyped behavior. The key to diagnosing autism in Joubert syndrome is to focus on social behaviors, particularly milestones typically achieved very early in life (eg, attending to human voices, showing objects of interest, enjoyment of social interactions). Implications for the role of the cerebellum in nonmotor behavior and for clinical management of Joubert syndrome also are discussed.     

Autistic social impairment in the siblings of children with pervasive developmental disorders

OBJECTIVE: Sibling recurrence risk in autism has been estimated to be approximately 10%. This study investigated subsyndromal autistic impairments among siblings of probands with pervasive developmental disorders. METHOD: The authors used the Social Responsiveness Scale to obtain quantitative assessments of autistic social impairment in three groups of proband-sibling pairs: 1) autistic children from multiple-incidence families and their closest in age nonautistic brothers (N=49 pairs); 2) children with any pervasive developmental disorder, including autism, and their closest-in-age brothers (N=100 pairs), and 3) children with psychopathology unrelated to autism and their closest-in-age brothers (N=45 pairs). RESULTS: Sibling Social Responsiveness Scale scores were continuously distributed and substantially elevated for both the autistic and pervasive developmental disorder groups. Highest scores (i.e., greatest impairment) were seen among siblings of autistic probands from multiple-incidence families, followed by siblings of probands with any pervasive developmental disorder, then siblings of probands with psychopathology unrelated to autism. CONCLUSIONS: Taken together with previous findings, these results support the notion that genetic susceptibility factors responsible for common, subsyndromal social impairments may be related to the causes of categorically defined pervasive developmental disorders.     

The Home TEACCHing Program for Toddlers with Autism

The study evaluated the efficacy a parent training intervention for children with autism based on the TEACCH model. Twenty families were randomly assigned to the treatment or waitlist group. All families were compared at pre- and post-treatment on formal dependent measures. Direct measures of behavior were compared across six matched pairs using a multiple baseline probe design. The results of the multiple baseline design showed robust support for improvement in child and parent behavior. Due to the sample size and short time frame, results of a repeated measures analysis of variance did not reach significance.     

Autistic disorder: current psychopharmacological treatments and areas of interest for future developments

Autistic disorder and the group of related conditions defined as pervasive developmental disorders are chronic neurodevelopmental disorders starting in early childhood and affecting a significant number of children and families. Although the causes and much of the pathophysiology of the disorder remain unknown, in recent years a number of available medication treatments have been identified as holding promise in alleviating some of the most disabling maladaptive behaviors, associated with pervasive developmental disorders. However these treatments do not address the core symptoms of the disease and oftentimes their side effects outweigh their benefits. Therefore there is substantial need for new medications that are safer and more effective in addressing the behavior symptoms of autism. The aim of this review is to highlight the available current pharmacotherapies and those emerging treatments with potential to enhance the treatment options of patients with pervasive developmental disorders.     

Variation in Early Developmental Course in Autism and its Relation with Behavioral Outcome at 3–4 Years of Age

The aims of the present study were to describe variations in the early course of development in autism by utilizing an in-depth parent interview that incorporated techniques to improve accuracy of parent recall, and to examine the relation between variations in early developmental course in autism and behavioral outcome at 3–4 years of age. The Early Development Interview, which consisted of questions about child’s behavior in several domains from birth through 2 years of age, was created and administered to parents of 72 3–4-year-old children with autism spectrum disorder and 34 3–4-year-old children with developmental delay, who were matched on mental and chronological age, and 39 1–4-year-old typically developing children, who were matched to the clinical groups on mental age. At 3–4 years of age, children were administered standardized measures (some clinician administered and some parent report); these included verbal and nonverbal IQ, autism symptom severity, and adaptive and aberrant behavior. Based on the Early Development Interview, children with autism spectrum disorder (ASD) were reported to have elevated symptoms in the social and regulatory domains by 3–6 months. By 12–15 months, parents of children with ASD reported significantly higher levels of social symptoms than parents of children with developmental delay. At 3–4 years of age, children with autism with early vs. late onset of symptoms, and with vs. without a history of loss of skills (regression) were not found to differ on standardized tests of verbal and nonverbal IQ and observational measures of autism symptom severity.     

Brief Report: Effects of Cognitive Behavioral Therapy on Parent-Reported Autism Symptoms in School-Age Children with High-Functioning Autism

This pilot study tested the effect of cognitive behavioral therapy (CBT) on parent-reported autism symptoms. Nineteen children with autism spectrum disorders and an anxiety disorder (7–11 years old) were randomly assigned to 16 sessions of CBT or a waitlist condition. The CBT program emphasized in vivo exposure supported by parent training and school consultation to promote social communication and emotion regulation skills. Parents completed a standardized autism symptom checklist at baseline and posttreatment/postwaitlist and 3-month follow-up assessments. CBT outperformed the waitlist condition at posttreatment/postwaitlist on total parent-reported autism symptoms (Cohen’s d effect size = .77). Treatment gains were maintained at 3-month follow-up. Further investigation of this intervention modality with larger samples and broader outcome measures appears to be indicated.     

Autism and Asperger syndrome: an overview

Autism and Asperger syndrome are diagnostic entities in a family of neurodevelopmental disorders disrupting fundamental processes of socialization, communication and learning, collectively known as pervasive developmental disorders. This group of conditions is among the most common developmental disorders, affecting 1 in every 200 or so individuals. They are also the most strongly genetically related among developmental disorders, with recurrence risks within sibships of the order of 2 to 15% if a broader definition of affectedness is adopted. Their early onset, symptom profile, and chronicity implicate fundamental biological mechanisms involved in social adaptation. Advances in their understanding are leading to a new social neuroscience perspective of normative socialization processes and specific disruptions thereof. These processes may lead to the emergence of the highly heterogeneous phenotypes associated with autism, the paradigmatic pervasive developmental disorder, and its variants. This overview focuses on the history, nosology, and the clinical and associated features of the two most well-known pervasive developmental disorders - autism and Asperger syndrome.