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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↗
PubMed2006

Automatic processing of emotional faces in high-functioning pervasive developmental disorders: An affective priming study.

This study examined automatic processing of emotional faces in individuals with high-functioning Pervasive Developmental Disorders (HFPDD) using an affective priming paradigm. Sixteen participants (HFPDD and matched controls) were presented with happy faces, fearful faces or objects in both subliminal and supraliminal exposure conditions, followed by Japanese ideographs for which the participants provided liking ratings. In the HFPDD group, affective priming was not found in either condition; the control group showed affective priming for both emotional faces under the subliminal condition and only for happy faces under the supraliminal condition. Results suggest that the social deficit in autism may derive in part from a failure in evaluating the emotional significance of emotional faces, a function for which the amygdala plays an important role.

Affect↗
PubMed2006

Sleep problems of children with pervasive developmental disorders: correlation with parental stress.

This study aimed to investigate the prevalence of sleep problems in Chinese children with pervasive developmental disorders (PDD) in Hong Kong and their relationship to parental stress. A cross-sectional survey was conducted in six child assessment centres. All parents of the children with PDD completed the Children's Sleep Habits Questionnaire, the Parenting Stress Index-Short Form, and questions on sleep practice. A total of 210 out of 250 questionnaires (response rate 84%) were returned. Mean age of the children was 3 years 6 months (SD 1 y 4 mo; range 2 y-7 y 7 mo; 168 males, 25 females). The prevalence of parent-defined sleep problems in various sleep domains ranged from 9.3 to 45.6%, with 67.9% of children having significant problems in at least one sleep domain. The most common problems reported were bedtime resistance and parasomnias. Similar sleep problems occurred in all the PDD subgroups. The factor most significantly associated with sleep problems was the occurrence of sleep problems before the age of 2 years. The parents of children with PDD with sleep problems experienced a higher level of stress than those whose children had no sleep problems. A high prevalence of significant sleep problems was reported in Chinese children in Hong Kong with PDD. A higher stress level among the parents of those children with PDD with sleep problems suggests the need for systematic early detection and management of sleep problems in children with PDD.

Child↗
PubMed2005

Retrospective assessment of atomoxetine in children and adolescents with pervasive developmental disorders.

A retrospective study was conducted to assess the effectiveness and tolerability of atomoxetine in children and adolescents with pervasive developmental disorders (PDD). An outpatient clinic registry of individuals with PDD was used to identify all children and adolescents who received atomoxetine over a period of 12 months. Patients were included if concomitant medications remained unchanged. Treatment response was assessed using the Global Improvement item of the Clinical Global Impressions scale (CGI-GI) based on the Conners Parent Rating Scale (CPRS) routinely completed by primary caretakers and other clinical information available in the registry. Twenty patients were identified, including 16 males and 4 females (age, 11.5 years; standard deviation, 3.5). Most patients (80%) were taking at least 1 concomitant medication. Treatment dose was 43.3 mg (standard deviation, 18.1) and duration was 19.5 weeks (standard deviation, 10.5). Twelve patients were judged to be responders, as defined by a score of 1 or 2 on the CGI-GI. Differences between baseline and the end of the trial period were observed in the following CPRS subscales: Conduct, hyperactivity, inattention, and learning. No differences were noted in the anxiety and psychosomatic subscales. One patient discontinued atomoxetine because of severe mood swings. Atomoxetine may be beneficial for treating secondary symptoms of PDD, and prospective open-label or double-blind, placebo-controlled studies are needed to assess its efficacy and safety.

Adolescent↗
PubMed1998

Sertraline in adults with pervasive developmental disorders: a prospective open-label investigation.

The short-term efficacy and tolerability of sertraline for adults with pervasive developmental disorders (PDDs) were assessed in this investigation. Forty-two adults with PDDs (autistic disorder, N = 22; Asperger's disorder, N = 6; and PDD not otherwise specified [NOS], N = 14) participated in a 12-week, open-label, systematic trial of sertraline. Behavioral ratings of repetitive symptoms, aggression, and social relatedness were obtained at baseline and after 4, 8, and 12 weeks of sertraline administration. Twenty-four (57%) of 42 patients showed significant improvement, primarily in repetitive and aggressive symptoms. Statistically significant changes in measures of social relatedness did not occur. Patients with autistic disorder and PDD NOS did significantly better than those with Asperger's disorder. Based on global improvement item criteria from the Clinical Global Impression Scale, 15 of 22 (68%) patients with autistic disorder, none of six (0%) patients with Asperger's disorder, and 9 of 14 (64%) patients with PDD NOS were categorized as treatment responders. Sertraline was well tolerated; no adverse cardiovascular effects, extrapyramidal symptoms, or seizures were identified. These findings suggested that sertraline may be an effective treatment for interfering repetitive and aggressive symptoms in adults with PDDs. Definitive statements about the efficacy and tolerability of sertraline for treating adults with PDDs must await results from double-blind, placebo-controlled trials. These preliminary results should not be generalized to include children and adolescents with PDDs.

1-Naphthylamine↗
PubMed1985

Developmental disorders. When to refer a child to a specialized center.

Primary care physicians need to be informed about and attuned to developmental problems in children. Developmental disorders present in infancy and childhood with characteristic symptoms that should alert the physician to the need for in-depth evaluation. This type of assessement can best be carried out in a medically based, multidisciplinary center with a team of professionals who act as consultants to and partners with the physician in caring for the child and family.

Child↗
PubMed2001

What framework should we use for understanding developmental disorders?

The neuropsychology of dyslexia has made great strides in the last decade. In particular, a consensus views dyslexia as a developmental disorder with a basis in the brain and in the genes, where the interaction of genetic and environmental factors is taken for granted. However, problems in defining the phenotype continue to bedevil research. The main conceptual problems can be expressed in three main questions: (a) Is dyslexia based on a specific brain abnormality or is it merely part of a continuum of atypical brain development? (b) When can we speak of comorbidity? (c) Why does so much individual variability occur? These questions can be tackled in a common framework that takes into account simultaneously three levels: the biological, the cognitive, and the behavioral.

Brain Damage, Chronic↗
PubMedDate not supplied

A second visually impaired, mentally retarded male with pervasive developmental disorder, Tourette disorder and Ganser's syndrome: diagnostic classification and treatment.

The authors report a second visually impaired, mentally retarded male who presents with symptoms consistent with atypical pervasive developmental disorder, Tourette disorder, and a syndrome of approximate answers (Ganser's syndrome). Both this case and an earlier reported case are significant in that they identify two children with strikingly similar long-standing symptoms and developmental histories. Since these findings may have broader relevance to children with multiple coexisting disorders, diagnostic and intervention strategies in this population are reviewed.

Adolescent↗
PubMed1991

Stressors experienced by family caregivers of children with pervasive developmental disorders.

The purpose of this study was to identify the perceived stressors experienced by parents who care for children with Pervasive Developmental Disorders. The relationship between demographics and overall stress was also examined. The most frequently cited stressor was difficulty arranging for and collaborating with professional and support services. Problems associated with the child's emotional and mental state were viewed as the most stressful of all. No demographic variables showed a significant relationship to degree of overall stress.

Adult↗
PubMed2002

Efficacy of porcine secretin in children with autism and pervasive developmental disorder.

Secretin, a gastrointestinal (GI) hormone, was reported in a preliminary study to improve language and behavior in children with autism/pervasive developmental disorder (PDD) and chronic diarrhea. To determine the efficacy of secretin, we completed a double-blind, placebo-controlled, crossover (3 weeks) study in children with autism/PDD and various GI conditions using a single dose of intravenous porcine secretin. Children with chronic, active diarrhea showed a reduction in aberrant behaviors when treated with the secretin but not when treated with the placebo. Children with no GI problems are unaffected by either secretin or placebo. The improvement seen with secretin in children with autism/PDD and chronic diarrhea suggests that there may be a subtype of children with autism/PDD who respond to secretin.

Autistic Disorder↗
PubMed2004

The comorbidity of Pervasive Developmental Disorder and Attention Deficit Hyperactivity Disorder: results of a retrospective chart review.

OBJECTIVE: To determine if a sample of children meeting diagnostic criteria for a Pervasive Developmental Disorder (PDD) display symptoms and impairment related to Attention Deficit Hyperactivity Disorder (ADHD) sufficient to warrant a comorbid diagnosis of ADHD. Further, do children with PDD displaying such symptoms demonstrate more impairment in daily life activities than those children only having PDD? METHOD: A retrospective chart review was conducted on children (N = 57) diagnosed with the PDD's of Autism or PDD-Not Otherwise Specified (PDD-NOS), or ADHD. Comparative analysis of questionnaire and neuropsychological test data was completed to determine the severity of ADHD-like symptoms presenting among children with PDD. RESULTS: From the pool of subjects having PDD with sufficient data (N = 27), 7 or 26% met DSM-IV criteria for the combined type of ADHD. Nine or 33% met diagnostic criteria for the Inattentive Type of ADHD and 11 or 41% did not demonstrate a significant number of ADHD symptoms to warrant a comorbid diagnosis of ADHD. Results indicate that a subgroup of children with PDD displaying significant ADHD-like symptoms may in fact have ADHD thus warranting a comorbid diagnosis of ADHD. Current data did not suggest children with PDD and the combined type of ADHD demonstrated significantly more impairment in daily life functioning than those children only having PDD. However, this appeared likely the result of small sample size. The data, however, does indicate such children experience more difficulties in daily situations as rated by parents and teachers. CONCLUSION: These findings reinforce clinical observations indicating that some children with PDD may also experience an independent comorbid condition of ADHD, suggesting that a comorbid diagnosis of ADHD with PDD be considered in such cases. If further findings are replicated, the current exclusionary DSM-IV-TR criteria of making such a comorbid diagnosis should be re-considered.

Attention Deficit Disorder with Hyperactivity↗
PubMed2006

Children's Yale-Brown Obsessive Compulsive Scale modified for pervasive developmental disorders.

OBJECTIVE: To examine the psychometric properties of the Children's Yale-Brown Obsessive Compulsive Scales (CYBOCS) modified for pervasive developmental disorders (PDDs). METHOD: Raters from five Research Units on Pediatric Psychopharmacology (RUPP) Autism Network were trained to reliability. The modified scale (CYBOCS-PDD), which contains only the five Compulsion severity items (range 0-20), was administered to 172 medication-free children (mean 8.2 +/- 2.6 years) with PDD (autistic disorder, n = 152; Asperger's disorder, n = 6; PDD not otherwise specified, n = 14) participating in RUPP clinical trials. Reliability was assessed by intraclass correlation coefficient (ICC) and internal consistency by Cronbach's alpha coefficient. Correlations with ratings of repetitive behavior and disruptive behavior were examined for validity. RESULTS: Eleven raters showed excellent reliability (ICC = 0.97). The mean CYBOCS score was 14.4 (+/- 3.86) with excellent internal consistency (alpha = .85). Correlations with other measures of repetitive behavior ranged from r = 0.11 to r = 0.28 and were similar to correlations with measures of irritability (r = 0.24) and hyperactivity (r = 0.25). Children with higher scores on the CYBOCS-PDD had higher levels of maladaptive behaviors and lower adaptive functioning. CONCLUSIONS: The five-item CYBOCS-PDD is reliable, distinct from other measures of repetitive behavior, and sensitive to change.

Antipsychotic Agents↗
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↗
PubMed1999

Beneficial effects of clonidine on severe self-injurious behavior in a 9-year-old girl with pervasive developmental disorder.

We report the successful treatment of persistent self-injurious behavior (SIB) in a 9-year-old girl with pervasive developmental disorder. The girl had inflicted severe tissue damage to her face, neck, and inner thighs due to pinching, scratching, and rubbing of her skin. Using a rating scale to quantify surface tissue damage produced by SIB, the number of bodily injuries, the intensity of skin trauma, and the projected risk of further physical harm decreased dramatically following the administration of clonidine that was titrated to a maximum dose of 0.4 mg daily. The girl's SIB showed marked improvement over a 24-month period of observation. Issues related to pharmacotherapy of SIB using alpha adrenergic agonists are discussed.

Adrenergic alpha-Agonists↗
PubMed1998

Timing of social gaze behavior in children with a pervasive developmental disorder.

The aim of the study was to compare social initiatives and gaze behavior in low-functioning children with a pervasive developmental disorder (PDD), high-functioning children with a PDD, children with a language disorder, and normally developing children. Behavior of the children was observed while they watched television and performed a playful task with a parent. Compared to the high-functioning children, the low-functioning children with a PDD showed fewer social initiatives. The high-functioning children with a PDD did not differ from the non-PDD control children in the number of social initiatives and gazes. However, in children with PDD, timing of social gaze proved to be different in that they had lower levels of visual checking before but not after a declarative pointing gesture. Furthermore, they had lower levels of returning gaze.

Attention↗
PubMed2002

A retrospective assessment of citalopram in children and adolescents with pervasive developmental disorders.

Although selective serotonin reuptake inhibitors have been used to treat symptoms of aggression and anxiety in children and adolescents with pervasive developmental disorders (PDDs), there are no published reports of the use of citalopram in this population. The purpose of this study was to examine the benefits and adverse effects of citalopram in a group of children and adolescents with PDDs. Target behaviors included aggression, anxiety, stereotypies, and preoccupations. Seventeen patients with PDDs (14 with autistic disorder, three with Asperger's disorder) (mean age = 9.4 +/- 2.9 years; range 4-15 years) were treated with citalopram for at least 2 months (mean duration of treatment = 7.4 +/- 5.3 months; range 1-15 months). Treatment was initiated at a low dose (5 mg daily) and was increased by 5 mg weekly as tolerated and as necessary. The mean final dose was 19.7 +/- 7.8 mg (range 5-40 mg). Outcome was based on a consensus between clinician and parents, using the Improvement item of the Clinical Global Impressions Scale as a guide. Ten (59%) children were judged to be much improved or very much improved regarding target behaviors. Core symptoms of PDDs (social interactions, communication) did not show clinically significant improvement. Citalopram was generally well tolerated, although four patients developed treatment-limiting adverse effects: two with increased agitation, one with insomnia, and one with possible tics. The results of this case series suggest that citalopram has beneficial effects on some interfering behaviors associated with PDDs with few adverse effects. Controlled trials are warranted.

Adolescent↗
PubMed2005

A double-blind, placebo-controlled study of valproate for aggression in youth with pervasive developmental disorders.

OBJECTIVE: The aim of this study was to study valproate efficacy and safety for aggression in children and adolescents with pervasive developmental disorders (PDD). METHODS: In this prospective double-blind, placebo-controlled study, 30 subjects (20 boys, 10 girls) 6-20 years of age with PDD and significant aggression were randomized and received treatment with valproate (VPA) or placebo (PBO) for 8 weeks as outpatients. Mean VPA trough blood levels were 75.5 mcg/mL at week 4 and 77.8 mcg/mL at week 8. RESULTS: No treatment difference was observed statistically between VPA and PBO groups. The Aberrant Behavior Checklist--Community Scale (ABC-C) Irritability subscale was the primary outcome measure (p = 0.65), and CGI--Improvement (p = 0.16) and OAS (p = 0.96) were secondary outcome measures. Increased appetite and skin rash were significant side effects. Only 1 subject was dropped from the study owing to side effects, notably a spreading skin rash, which then resolved spontaneously. Two subjects receiving VPA developed increased serum ammonia levels, one with an associated parent report of slurred speech and mild cognitive slowing. Poststudy, of 16 VPA and PBO subjects receiving VPA, 10 subjects demonstrated sustained response, 4 of whom later attempted taper, with significant relapse of aggression. CONCLUSION: The present negative findings cannot be viewed as conclusive, partly owing to the large placebo response, subject heterogeneity, and size of the groups. Larger studies are needed to expand upon these findings.

Adolescent↗
PubMed2006

A prospective, open-label trial of memantine in the treatment of cognitive, behavioral, and memory dysfunction in pervasive developmental disorders.

BACKGROUND: This pilot study examined the effectiveness of memantine hydrochloride in improving cognitive functioning and behavioral symptoms in children with pervasive developmental disorders (PDDs). METHOD: Subjects aged 3-12 years inclusive were enrolled in this 8-week, open-label study. Expressive and receptive language, nonverbal IQ, and nonverbal memory measures were administered at baseline and after 8 weeks of treatment with 0.4 mg/kg of memantine hydrochloride. Throughout the study, the Aberrant Behavior Checklist (ABC) was sent in weekly by parents as a measure of behavioral change. RESULTS: Twelve of 14 subjects completed the study. Significant improvement from baseline was noted on the memory test (Children's Memory Scale Dot Learning Subtest). There were no significant differences from baseline on measures of expressive or receptive language or nonverbal IQ. There were significant improvements on a number of ABC subscales, including hyperactivity, lethargy, and irritability. There were no overall significant statistical differences from baseline on the Clinical Global Improvement-Severity (CGI-S) scale. On the Clinical Global Improvement-Improvement (CGI-I), 4 of 14 subjects showed minimal improvement, and none was deemed "much-improved" or "very much improved." CONCLUSIONS: This small, prospective, open-label study suggests that memantine may be useful in the treatment of memory functioning and some behavioral symptoms in PDDs. The investigators did not see the same degree of change as endorsed by caretakers. Controlled studies are needed to substantiate and clarify these preliminary findings.

Child↗