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PubMed1991

Clinical and genetic relationships between autism-pervasive developmental disorder and Tourette syndrome: a study of 19 cases.

Children with autism or pervasive developmental disorder (PDD) and Tourette syndrome (TS) share a number of symptoms. Forty-one cases have been reported in which PDD patients subsequently developed TS. We term this PDD----TS. We describe an additional 16 such patients plus 3 families where a close relative of a TS proband had autism. There was a high frequency of alcoholism, drug abuse, obsessive-compulsive, and other behavior disorders in the relatives of these patients. This frequency was virtually identical to that observed in relatives of individuals with TS only. We suggest there is an intimate genetic, neuropathologic relatedness between some cases of PDD and TS. Many observations have led us to suggest that the genetic defect in TS may be a mutation of tryptophan oxygenase and that TS is inherited as a semidominant semirecessive trait, i.e., homozygosity for a common gene which shows some expression in the heterozygous state. We propose that some types of PDD are inherited in the same fashion and by the same gene. This would explain the similarity of symptoms, frequent evolution of PDD into TS, the apparent recessive inheritance of PDD despite no increase in consanguinity, the high frequency of behavior problems in the relatives of PDD----TS patients and the serotonin abnormalities.

Adolescent↗

PubMed2001

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.

Autistic Disorder↗

PubMed2003

Childhood autism rating scale--Tokyo version for screening pervasive developmental disorders.

To assess the utility of the Childhood Autism Rating Scale - Tokyo Version (CARS-TV), its total score was compared among 430 children with DSM-IV per subgroup (i.e. autistic disorder (AD), childhood disintegrative disorder (CDD), Asperger's disorder, and pervasive developmental disorders (PDD) not otherwise specified (PDDNOS)). Values of Cronbach's alpha were 0.91 for the PDD group and 0.89 for the non-PDD mental retardation (MR) group, and 0.93 for both groups combined. The total score was significantly higher in PDD (mean = 30.1, SD = 4.5) than in non-PDD MR (mean = 22.9, SD = 3.3), t(503) = 13.7, P< 0.0001. The cut-off to distinguish PDD from non-PDD MR was 25.5/26, with sensitivity, specificity, positive predictive value and negative predictive value of 0.86, 0.83, 0.97 and 0.50, respectively. The total score differed significantly among the four groups, with CDD and AD being significantly higher than both PDDNOS and Asperger's disorder, PDDNOS being significantly higher than Asperger's disorder and no significant difference between CDD and AD. The cut-off to distinguish AD from PDDNOS was 30/30.5, with sensitivity, specificity, positive predictive value and negative predictive value of 0.71, 0.75, 0.77 and 0.69, respectively. CARS-TV seems to be a useful instrument for differentiating between PDD and non-PDD MR and between AD and PDDNOS, although further replication is needed.

Adolescent↗

PubMed2004

The incidence and prevalence of pervasive developmental disorders: a Danish population-based study.

BACKGROUND: Based on prevalence studies and the few incidence studies of pervasive developmental disorders (PDDs) the prevalence and incidence of these disorders have been claimed to be increasing. METHOD: The annual and age-specific prevalence and incidence rates of childhood autism, atypical autism, Asperger's disorder, and pervasive developmental disorder not otherwise specified (PDD-NOS) in Denmark during the period 1971--2000 in children younger than 10 years were estimated using data from the Danish Psychiatric Central Register. RESULTS: A total of 2.4 million children younger than 10 years were followed and 2061 cases with the PDDs studied were identified. Generally, the prevalence and incidence rates of the PDDs studied were stable until the early 1990s after which an increase in the occurrence of all disorders was seen, until 2000. The annual incidence rate per 10000 children younger than 10 years was 2.0 for childhood autism, 0.7 for atypical autism, 1.4 for Asperger's disorder, and 3.0 for PDD-NOS in 2000. We calculated a 'corrected' prevalence of childhood autism at 11.8, atypical autism at 3.3, Asperger's disorder at 4.7, and PDD-NOS at 14.6 per 10,000 children younger than 10 years on 1 January 2001. CONCLUSIONS: We found that the estimated prevalences of the PDDs studied were probably underestimated. Furthermore, the increasing prevalence and incidence rates during the 1990s may well be explained by changes in the registration procedures and more awareness of the disorders, although a true increase in the incidence cannot be ruled out.

Age Factors↗

PubMed2005

Symptoms related to ADHD observed in patients with pervasive developmental disorder.

To elucidate attention-deficit/hyperactivity disorder (ADHD)-related factors observed in high-function pervasive developmental disorder (PDD) and their impact on daily life, we classified high-function PDD patients according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for ADHD with the exception of the exclusion criteria (coexistence with PDD), and studied the relationship between ADHD-related aspects and daily behavior problems using the Child Behavior Checklist (CBCL). The subjects were divided into two groups: Group 1, eight patients less than 6 years of age; and Group II, eight patients 6 years of age and older. Six patients in Group II met the criteria for ADHD. Five of them were classified as having the predominantly inattentive type of ADHD, and the remaining patient exhibited the combined type. However, no patient in Group I met the criteria for ADHD, suggesting the low sensitivity of the DSM-IV criteria for assessing the inattentiveness of preschoolers. The analyses of the correlation between corresponding items in the DSM-IV criteria and CBCL scores suggested that ADHD-related symptoms in high-function PDD patients have an impact on their daily lives.

Attention Deficit Disorder with Hyperactivity↗

PubMed2006

Saccadic movements using eye-tracking technology in individuals with autism spectrum disorders: pilot study.

OBJECTIVE: To verify differences in the visual scanning strategies between pervasive developmental disorders (PDD) and controls when they are observing social and non-social pictures. METHOD: PDD group (PDDG) comprised by 10 non-retarded subjects (age from 4 to 41) and age-matched control group (CG). Nine social pictures with human beings (including two pictures of cat mask), and 3 nonsocial pictures of objects were presented for 5 seconds. Saccadic movements and fixation were recorded with equipment EyeGaze (LC Technologies Inc.). RESULTS: PDDG (mean=292.73, SE=67.62) presented longer duration of saccadic movements for social pictures compared to CG (mean=136.06, SE=14.01) (p=0.04). The CG showed a higher number of fixations in the picture 7 (a women using a cat mask, with the eyes erased) (CG: mean=3.40; PDDG: mean=1.80; p=0.007). CONCLUSION: The results suggest differences in strategies that PDD explore human picture. Moreover, these strategies seem not to be affected by the lack of expected part of the face (the eyes).

Adolescent↗

PubMed2005

Incidence of autism spectrum disorders in children in two Australian states.

AIM: To ascertain the incidence of autism spectrum disorders in Australian children. SETTING: New South Wales (NSW) and Western Australia (WA), July 1999 to December 2000. DESIGN: Data were obtained for WA from a prospective register and for NSW by active surveillance. MAIN OUTCOME MEASURES: Newly recognised cases of autism spectrum disorders (defined as autistic disorder, Asperger disorder and pervasive developmental disorder not otherwise specified [PDD-NOS]) in children aged 0-14 years; incidence was estimated in 5-year age bands (0-4 years, 5-9 years, 10-14 years). RESULTS: In WA, 252 children aged 0-14 years were identified with autism spectrum disorder (169 with autistic disorder and 83 with Asperger disorder or PDD-NOS). Comparable figures in NSW were 532, 400 and 132, respectively. Most children were recognised with autistic disorder before school age (median age, 4 years in WA and 3 years in NSW). Incidence of autistic disorder in the 0-4-years age group was 5.5 per 10,000 in WA (95% CI, 4.5-6.7) and 4.3 per 10,000 in NSW (95% CI, 3.8-4.8). Incidence was lower in older age groups. The ratio of all autism spectrum disorders to autistic disorder alone was 1.5:1 in WA and 1.3:1 in NSW, and rose with age (1.8:1 and 2.9:1 in 10-14-year-olds in WA and NSW, respectively). CONCLUSIONS: These are the first reported incidence rates for autism for a large Australian population and are similar to rates reported from the United Kingdom. Ongoing information gathering in WA and repeat active surveillance in NSW will help to monitor any future changes.

Adolescent↗

PubMed2001

Prolactin levels in young children with pervasive developmental disorders during risperidone treatment.

Although hyperprolactinemia is a common side effect during risperidone treatment in adult patients, no information is available on young children. The aim of this study is to report on serum prolactin levels in 25 young autistic children (22 males and 3 females, age range 3.9-7 years, mean age 4.10 years) during treatment with risperidone (dosage range 0.25-0.90 mg/day, mean dosage 0.52 mg/day). Prolactin levels were measured at baseline and after 10 weeks of treatment. The clinical outcome measure used was the Clinical Global Impression-Improvement. Serum prolactin was 9.77 +/- 3.94 ng/mL at baseline and 25.92 +/- 13.9 ng/mL during the 10th week of treatment (p < 0.001). Six children (24%) showed prolactin levels lower than 15 ng/mL, which is the upper normal level; eight children (28%) had prolactin levels higher than two times the upper limit (30 ng/mL). Hyperprolactinemia did not show significant correlations with age, weight, or risperidone dosage. There was no relation with clinical outcome. Dose reduction of risperidone resulted in a decrease of prolactin levels. None of the children showed clinical signs of hyperprolactinemia. Given the paucity of available data on potential effects of long-term hyperprolactinemia, a monitoring of prolactin during treatment with risperidone and other typical and atypical antipsychotics may be warranted.

Age Factors↗

PubMed2005

Serotonin transporter intron 2 polymorphism associated with rigid-compulsive behaviors in Dutch individuals with pervasive developmental disorder.

Two putatively functional polymorphisms of the serotonin transporter gene (HTT, SLC6A4) were examined for associations with risk for pervasive developmental disorders (PDDs) and specific autism phenotypes. Dutch patients diagnosed with PDD (N = 125, age range 5-20 years, DSM-IV-TR based criteria, ADI-R and ADOS behavioral assessments) and their parents (N = 230) were genotyped for promoter ins/del (5-HTTLPR) and intron 2 variable number of tandem repeats (VNTR) alleles. Using the transmission disequilibrium test (TDT), no disorder-specific preferential transmission of promoter (long and short) or intron 2 (10- and 12-repeat) alleles was observed. However, multivariate analysis of continuous autism-related behavioral measures revealed that subjects with intron 2 12/12 genotype were significantly more impaired in the rigid-compulsive domain (P = 0.008). Quantitative TDT (QTDT) analysis also showed significant association of the intron 2 VNTR 12-repeat allele with rigid-compulsive behavior (P = 0.015). These results suggest that intron 2 VNTR alleles or nearby polymorphisms in linkage disequilibrium may play a role in specific aspects of the behavioral phenotype of autism.

Adolescent↗

PubMed1998

Difficulties in the understanding of false belief: specific to autism and other pervasive developmental disorders?

The present study examined the performance on a false belief task of atypical autistic children, i.e., children with a pervasive developmental disorder not otherwise specified (n = 50), socially immature children (n = 50), and normal children (n = 50). Children were shown a chocolate box and its unexpected content, i.e., a pencil, and then required to indicate what a friend would say about the content of the box. Results can be summarized: (1) over-all, 3-year-old children performed less well than children of 6 years. (2) Responses of 3-year-old atypical autistic and socially immature children did not differ significantly from those of normal children of the same age. (3) At age 6, normal children performed better than atypical autistic and socially immature children. (4) In general, no differences in performance between atypical autistic and socially immature children were found, and (5) their performance was linked to intelligence. The results support prior findings that atypical autistic children find it difficult to understand false beliefs; however, this difficulty does not seem to be specific for (atypical) autism, but might be a common feature of social immaturity in general.

Autistic Disorder↗

PubMed2001

A naturalistic open-label study of mirtazapine in autistic and other pervasive developmental disorders.

OBJECTIVE: The aim of this study was to conduct a naturalistic, open-label examination of the efficacy and tolerability of mirtazapine (a medication with both serotonergic and noradrenergic properties) in the treatment of associated symptoms of autism and other pervasive developmental disorders (PDDs). METHODS: Twenty-six subjects (5 females, 21 males; ages 3.8 to 23.5 years; mean age 10.1 +/- 4.8 years) with PDDs (20 with autistic disorder, 1 with Asperger's disorder, 1 with Rett's disorder, and 4 with PDDs not otherwise specified were treated with open-label mirtazapine (dose range, 7.5-45 mg daily; mean 30.3 +/- 12.6 mg daily). Twenty had comorbid mental retardation, and 17 were taking concomitant psychotropic medications. At endpoint, subjects' primary caregivers were interviewed using the Clinical Global Impressions (CGI) scale, the Aberrant Behavior Checklist, and a side-effect checklist. RESULTS: Twenty-five of 26 subjects completed at least 4 weeks of treatment (mean 150 +/- 103 days). Nine of 26 subjects (34.6%) were judged responders ("much improved" or "very much improved" on the CGI) based on improvement in a variety of symptoms including aggression, self-injury, irritability, hyperactivity, anxiety, depression, and insomnia. Mirtazapine did not improve core symptoms of social or communication impairment. Adverse effects were minimal and included increased appetite, irritability, and transient sedation. CONCLUSIONS: Mirtazapine was well tolerated but showed only modest effectiveness for treating the associated symptoms of autistic disorder and other PDDs.

Adolescent↗

PubMed1999

Familial factors influence level of functioning in pervasive developmental disorder.

OBJECTIVE: To determine whether siblings with pervasive developmental disorders (PDD) tend to have the same type and number of PDD symptoms or a similar level of functioning. METHOD: The familial correlations for PDD subtype, symptom totals, adaptive behaviors, and nonverbal IQ were calculated for 94 children with PDD from 46 families. RESULTS: On variables measuring PDD symptoms, only impairments in nonverbal communication and verbal/nonverbal status tended to run true within families. There was no familial aggregation of PDD subtype. In contrast, measures of nonverbal IQ and adaptive behaviors in socialization and communication showed a moderate degree of familial resemblance. The degree of familial resemblance did not change if the analysis was restricted only to those families in which both affected children met criteria for autism. CONCLUSION: Insofar as the familial resemblance seen in PDD is due to genetic factors, these data provide some evidence that higher- and lower-functioning PDD children may arise from separate genetic mechanisms. Current gene-mapping studies of PDD may need to take this evidence of genetic heterogeneity into account.

Activities of Daily Living↗

PubMed2003

Low-frequency hearing assessment by middle latency responses in children with pervasive developmental disorder.

OBJECTIVE: In this study, we assessed middle latency responses (MLR) in children diagnosed with pervasive developmental disorder (PDD) in order to detect low-frequency auditory thresholds. METHODS: 35 children, 25 males and 10 females, aged below 5, diagnosed with PDD were referred to rule out any possible hearing deficit. Audiologic evaluation included free-field testing, tympanometry, and both MLR and auditory brainstem responses. A control group of 15 normal children matched for sex and age were used. RESULTS: In 9 out of 35 children (25%), low-frequency sensory hearing loss was revealed. The hearing loss was unilateral in seven children and bilateral in two, and varied from slight to severe. In four out of the nine cases (44%), parents had not suspected hearing loss, since these children always responded to sound. CONCLUSIONS: Among children diagnosed with PDD a significant proportion (25%) was affected by low-frequency sensory hearing loss, detected by MLR. In these children, when low-frequency hearing loss was found bilateral or severe unilateral, aural rehabilitation was initiated in order to improve their responses to auditory stimuli and their impaired communication with the environment. PDD children, even if their reaction to sound is normal, must be referred to thorough audiometric evaluation while low-frequency hearing level should always be tested.

Acoustic Impedance Tests↗

PubMed2004

Psychiatric symptoms in preschool children with PDD and clinic and comparison samples.

OBJECTIVE: This study describes and compares the severity of DSM-IV symptoms in preschool children with diagnosed pervasive developmental disorder (PDD), clinic controls, and two community-based samples. METHOD: Parents (/and teachers) completed the early child inventory-4 (ECI-4), a DSM-IV-referenced rating scale for four samples: PDD (n = 172/160) and nonPDD psychiatric clinic referrals (n=135/101) and youngsters in regular (n=507/407) and special (n =64/140) early childhood programs. Children ranged in age from 3 to 5 years old. RESULTS: With the exception of conduct problems, the PDD group generally received higher symptom severity ratings than the regular early childhood group, but the pattern of differences compared with the other two groups often varied by type of symptom and informant. Teachers rated the PDD and nonPDD clinic groups as having equally severe ADHD and oppositional defiant disorder symptoms. Teachers rated the PDD group as having more severe anxiety and depression symptoms than parents. The Asperger group was rated by both informants as more oppositional than the autism and PDDNOS subgroups. Teachers rated males in the regular early childhood sample as having more severe ADHD and aggressive symptoms than females, but this was not the case for the PDD sample. CONCLUSION: Preschoolers with PDD exhibit more severe DSM-IV psychiatric symptoms than children in regular and special early childhood programs, and to some extent nonPDD psychiatric referrals. The concept of comorbidity warrants further exploration, as does informant-specific syndromes as validators of diagnostic constructs.

Child Development Disorders, Pervasive↗

PubMed2004

Aripiprazole for maladaptive behavior in pervasive developmental disorders.

OBJECTIVE: The aim of this study was to obtain preliminary data regarding the effectiveness and tolerability of aripiprazole in the treatment of children and adolescents with a pervasive developmental disorder (PDD). METHOD: Five youths (mean age, 12.2 years; range, 5-18 years) meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) criteria for a PDD received a naturalistic, open-label trial of aripiprazole (mean dosage, 12.0 mg/day; range, 10-15 mg/day) for a minimum of 8 weeks (mean duration, 12 weeks; range, 8-16 weeks). RESULTS: All 5 patients were judged to be responders, as determined by a Clinical Global Impressions-Improvement (CGI-I) scale rating of "much improved" or "very much improved." Aripiprazole was well tolerated. No extrapyramidal symptoms or clinically significant changes in heart rate or blood pressure occurred during the short-term trials. Two of 5 patients experienced mild somnolence. Two subjects lost weight, 2 subjects had no change, and 1 subject gained weight (mean change, -8.2 lbs; range, -30 to +1 lb). The weight loss was likely the result of the discontinuation of atypical antipsychotics that had led to significant weight gain. CONCLUSIONS: This case series describes the effectiveness of aripiprazole in the treatment of maladaptive behaviors in 5 patients with a PDD. No significant adverse effects emerged during these short-term trials. Additional research is needed to support these preliminary findings.

Adolescent↗

PubMed2001

Pervasive developmental disorders in preschool children.

CONTEXT: Prevalence rates of autism-spectrum disorders are uncertain, and speculation that their incidence is increasing continues to cause concern. OBJECTIVE: To estimate the prevalence of pervasive developmental disorders (PDDs) in a geographically defined population of preschool children. DESIGN, SETTING, AND PARTICIPANTS: Survey conducted July 1998 to June 1999 in Staffordshire, England. The area's 15 500 children aged 2.5 to 6.5 years were screened for developmental problems. Children with symptoms suggestive of a PDD were intensively assessed by a multidisciplinary team, which conducted standardized diagnostic interviews and administered psychometric tests. MAIN OUTCOME MEASURE: Prevalence estimates for subtypes of PDDs. RESULTS: A total of 97 children (79.4% male) were confirmed to have a PDD. The prevalence of PDDs was estimated to be 62.6 (95% confidence interval, 50.8-76.3) per 10 000 children. Prevalences were 16.8 per 10 000 for autistic disorder and 45.8 per 10 000 for other PDDs. The mean age at diagnosis was 41 months, and 81% were originally referred by health visitors (nurse specialists). Of the 97 children with a PDD, 25.8% had some degree of mental retardation and 9.3% had an associated medical condition. CONCLUSIONS: Our results suggest that rates of PDD are higher than previously reported. Methodological limitations in existing epidemiological investigations preclude interpretation of recent high rates as indicative of increased incidence of these disorders although this hypothesis requires further rigorous testing. Attention is nevertheless drawn to the important needs of a substantial minority of preschool children.

Autistic Disorder↗

PubMed2001

[Methylphenidate therapy in 141 patients with hyperkinetic disorder or with pervasive developmental disorder and hyperkinesia].

The efficacy and adverse reactions produced by methylphenidate (MPD) therapy were evaluated in 141 patients with hyperkinetic disorder or pervasive developmental disorder (PDD) with hyperkinesia. Ninety-nine patients were followed for 1 to 5 years to determine if the treatment could be continued and if the patients' adaptation to their environment improved. The results showed that the MPD therapy was effective in 93% of patients whose IQ was > 80 and in 70% whose IQ was < or = 80. The efficacy was not significantly different between patients with PDD and those without PDD. Of the patients in whom the MPD therapy was effective, the majority received a MPD dosage of 0.3 mg/kg once every morning. Adverse reactions, such as excitability, nausea or anorexia, and insomnia were reported in 23% of the patients. Although this figure was not negligible, no serious events occurred. Seizure induction was suspected in 2 patients. Many of the patients (53/83) in whom the MPD treatment was effective continued to receive the treatment throughout the follow-up period. By the time that the conditions were alleviated to the extent that the treatment could be stopped, the patients had become well adapted to their environment. However, in many other cases, adaptation was unsatisfactory. In these cases, psycosocial interventions were necessary, even if the MPD therapy was effective.

Adolescent↗

PubMed2006

Repetitive and stereotyped behaviours in pervasive developmental disorders.

BACKGROUND: Repetitive and stereotyped behaviours are a heterogeneous group of behaviours present in many neuropsychiatric disorders. Despite their core significance in PDD, it is not clear whether there are distinct groups of these behaviours with different specificity to autism. METHODS: A two-factor model of the repetitive behaviours, namely sensory/motor (lower-order) and cognitive rigidity (higher-order), was conceptualised. The model's goodness of fit to the data was examined in a clinic population of children with PDD, with and without mental retardation, and of those with only mental retardation (MR). RESULTS: Subjects with PDD had higher rates of all repetitive behaviours compared to those with MR only. The existence of two independent 'lower-order' and 'higher-order' sub-groups of the repetitive behaviours was confirmed only in the MR group. The lower-order behaviours appear to be associated more with global developmental problems, whereas the higher-order behaviours were significantly associated with ruminations in the PDD group. CONCLUSIONS: This study suggests that there may be two distinct sub-groups of repetitive behaviours whereby the sensory and motor repetitive behaviours are generally associated with lower developmental age and less specific to the autistic syndrome whereas the 'higher-order' behaviours may be a more 'autism specific' feature. The co-occurrence of the lower- and higher-order behaviours in PDD might reflect the end result of diffuse altered neural networks in these disorders thus being a specific feature of PDD. There is a need for more systematic studies of these behaviours not only in autistic disorders but also in other neuropsychiatric disorders.

Child↗