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PubMed2002

Serotonin transporter gene promoter variants do not explain the hyperserotoninemia in autistic children.

Autism is a biologically-heterogeneous disease. Distinct subgroups of autistic patients may be marked by intermediate phenotypes, such as elevated serotonin (5-HT) blood levels, potentially associated with different underlying disease mechanisms. This could lead to inconsistent genetic association results, such as those of prior studies on serotonin transporter (5-HTT) gene promoter variants and autistic disorder. Contributions of 5-HTT gene promoter alleles to 5-HT blood levels were thus investigated in 134 autistic patients and 291 first-degree relatives. Mean 5-HT blood levels are 11% higher in autistic patients carrying the L/L genotype, compared to patients with the S/S or S/L genotype; this trend is not observed in first-degree relatives. The probability of inheriting L or S alleles is significantly enhanced in patients with 5-HT blood levels above or below the mean, respectively (P < 0.05), but quantitative TDT analyses yield a non-significant trend (P = 0.10), as this polymorphism explains only 2.5% of the variance in 5-HT blood levels of autistic patients. In conclusion, 5-HTT gene promoter variants seemingly exert a small effect on 5-HT blood levels in autistic children, which largely does not account for hyperserotoninemia. Nonetheless, the inconsistent outcome of prior association studies could partly stem from a selection bias of hyper- or hypo-serotoninemic probands.

Autistic Disorder↗

PubMed1990

Fragile X syndrome, DSM-III-R, and autism.

Although reports of autistic behavior in fragile X males have been published for 8 years, there is little information about specific behaviors shown by fragile X males that are suggestive of the diagnosis of autism. The new diagnostic criteria for autistic disorder contained in the DSM-III-R provided the opportunity for more closely investigating the topography of autistic behavior in 17 fragile X males and the effects of age and IQ on its occurrence. The criteria most frequently met by these subjects were related to deficits in social interaction with peers, abnormalities in verbal and nonverbal communication, stereotypic motor behavior, and unusual responses to sensory stimuli. Fragile X subjects did not frequently show abnormalities in attachment behaviors and reciprocal interaction with caregivers. There were no discernable age or IQ effects. The importance and implications of these findings are discussed and the need for greater exploration of autism "subtypes" is emphasized.

Adolescent↗

PubMed2005

Post-traumatic stress disorder in young people with intellectual disability.

BACKGROUND: Post-traumatic stress disorder (PTSD) is common and treatable. There is extensive research on people of average intelligence yet little on individuals with developmental disabilities. METHODS: We report two people with intellectual disability (ID) who experienced PTSD. The relevance of their developmental difficulties, social and communication profiles, attentional skills, and causes of these, to their presentations is discussed. RESULTS: Both individuals have fragile X syndrome and severe ID. One has Diagnostic and Statistical Manual - 4th Edition (DSM-IV) autistic disorder; the other DSM-IV attention deficit-hyperactivity disorder. They experienced developmental and psychological regressions, new challenging behaviours and exacerbations of existing ones coincident with emotional trauma. PTSD symptoms and phenomena were identifiable despite intellectual and communicatory impairments. CONCLUSION: Presentation of PTSD is influenced by degree and cause of ID, social circumstances, social and communicatory skills, nature and timing of traumatic experience and subsequent management. The paucity of literature suggests it is missed frequently in individuals with ID who risk having problems misattributed to other causes with potential for inappropriate interventions.

Adolescent↗

PubMed1997

Are deficits in the decoding of affective cues and in mentalizing abilities independent?

It has been hypothesized that deficits in theory of mind (ToM) and emotion recognition abilities in subjects with autisticlike disorders are independent. We examined the relationships between deficits in the various social cognitive domains in children with an autistic disorder (N = 20), in children with a pervasive developmental disorder not otherwise specified (PDDNOS) (N = 20), and in psychiatric control (N = 20) and normal children (N = 20). The clinical groups were matched person-to-person on age and verbal IQ. The clinical children were 8-18 years old, the normal children 8-13 years old. The test battery included tasks for the matching and the context recognition of emotional expressions, and a set of first- and second-order ToM tasks. ToM and emotion recognition functioning proved to be better integrated in the non-PDD children than in the PDD children, but also in the PDD children significant correlations were found between ToM and emotion recognition measures.

Adolescent↗

PubMed1994

Comprehensive management of trichotillomania in a young autistic girl.

The coexistence of trichotillomania and autistic disorder has rarely been reported in psychiatric literature. The current study describes successful treatment of trichotillomania in a young autistic girl, using combined clomipramine and behavioral therapy. Neither behavioral therapy, clomipramine, methylphenidate, buspirone, nor naltrexone was effective in monotherapeutic trials. We postulate a synergistic effect of combined treatment with clomipramine and behavioral therapy, suggesting that both pharmacological and behavioral treatment of hair pulling may be necessary for many patients. This model is consistent with the extant literature and suggests that future clinical trials of clomipramine for trichotillomania, in both developmentally disabled and normal subjects, must evaluate this multimodal approach.

Autistic Disorder↗

PubMed1999

Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive developmental disorder.

BACKGROUND: Secretin is a peptide hormone that stimulates pancreatic secretion. After recent publicity about a child with autism whose condition markedly improved after a single dose of secretin, thousands of children with autistic disorders may have received secretin injections. METHODS: We conducted a double-blind, placebo-controlled trial of a single intravenous dose of synthetic human secretin in 60 children (age, 3 to 14 years) with autism or pervasive developmental disorder. The children were randomly assigned to treatment with an intravenous infusion of synthetic human secretin (0.4 microg per kilogram of body weight) or saline placebo. We used standardized behavioral measures of the primary and secondary features of autism, including the Autism Behavior Checklist, to assess the degree of impairment at base line and over the course of a four-week period after treatment. RESULTS: Of the 60 children, 4 could not be evaluated - 2 received secretin outside the study, and 2 did not return for follow-up. Thus, 56 children (28 in each group) completed the study. As compared with placebo, secretin treatment was not associated with significant improvements in any of the outcome measures. Among the children in the secretin group, the mean total score on the Autism Behavior Checklist at base line was 59.0 (range of possible values, 0 to 158, with a larger value corresponding to greater impairment), and among those in the placebo group it was 63.2. The mean decreases in scores over the four-week period were 8.9 in the secretin group and 17.8 in the placebo group (mean difference, -8.9; 95 percent confidence interval, -19.4 to 1.6; P=0.11). None of the children had treatment-limiting adverse effects. After they were told the results, 69 percent of the parents of the children in this study said they remained interested in secretin as a treatment for their children. CONCLUSIONS: A single dose of synthetic human secretin is not an effective treatment for autism or pervasive developmental disorder.

Adolescent↗

PubMed1994

Sampling the form of inner experience in three adults with Asperger syndrome.

Three adults with Asperger syndrome were invited to talk about their inner experiences, using an experience sampling and interview technique. They reported thoughts primarily or solely in the form of images. By contrast, normal adults previously tested with this technique reported inner experiences of a variety of forms. The present report suggests the feasibility and potential interest of the experience sampling method with high-functioning individuals with autistic disorder.

Adaptation, Psychological↗

PubMed1995

Siblings of a child with autism, with mental retardation and with a normal development.

A total of 60 children between 8 and 15 years of age participated in this project, 20 of whom had a sibling with autism, 20 a sibling with mental retardation and 20 a non-disabled sibling. The children were questioned about their sibling relationship and their experiences of stress. The children with a sibling with autism also completed a questionnaire on their knowledge of the autistic syndrome. Analyses revealed that the three groups were basically similar in their ratings of the frequency of stressors involving their siblings. There was a trend for children with a disabled brother or sister to rate their relationship with the sibling more positively. Correlational analyses revealed an association between both stressor frequency and appraisal and the evaluation of the relationship with the brother or sister. Siblings of children with autism had a fair understanding of the autistic syndrome. In this group, there was also an association between the children's knowledge of the autistic disorder and the quality of the sibling relationship.

Adolescent↗

PubMed1996

Psychiatric disorders in children and adolescents with mental retardation and active epilepsy.

OBJECTIVE: To assess the prevalence and types of psychiatric disorders in a representative sample of school-age children with the combination of mental retardation (MR) and active epilepsy. SUBJECTS AND METHODS: Ninety-eight children were identified with MR and active epilepsy in a population-based study from Göteborg, Sweden, which has a general population at risk of 48873 children. They were born between 1975 and 1986 and were 8 to 16 years old at the time of psychiatric examination. Five children had died, 3 had parents who declined participation, and 90 were clinically examined. RESULTS: Fifty-three children (59%) had at least 1 psychiatric diagnosis, and the conditions in 30 (33%) could not be classified because of profound severe MR. Twenty-four children (27%) had autistic disorder, and another 10 (11%) had an autisticlike condition. The combination of MR, active epilepsy, and autism or an autisticlike condition occurred at a rate of 0.07% in the general population. The most common seizure types in the group with autism or an autisiclike condition were complex partial, atypical absence, myoclonic, and tonic-clonic. CONCLUSIONS: Children with MR and active epilepsy suffered from a psychiatric disorder in a majority of those cases in which the children had enough skills and mobility to exhibit behavioral and emotional problems. Many such problems had been undiagnosed despite parental concern and the conviction that the psychiatric problems were the most burdensome in many cases. Neurologists and psychiatrists need to develop better programs for the adequate management of psychiatric disorders in this population.

Adolescent↗

PubMed2004

The factor structure of autistic traits.

BACKGROUND: Although DSM-IV requires symptoms in three criterion domains for a diagnosis of autistic disorder, the extent to which those domains are phenotypically independent is an unanswered and important question. The identification of 'endophenotypes' of the autistic syndrome may be very useful for genetic and neurobiologic studies of autism, but only if they represent truly independent sub domains of the disorder. METHODS: In this study we examined the factor structure of autistic traits using data from 226 child psychiatric patients with and without pervasive developmental disorders, employing cluster analysis of data from the Autism Diagnostic Interview-Revised (ADI-r) and principal components factor analysis of data from the Social Responsiveness Scale (SRS, a quantitative genetic measure of autistic traits formerly known as the Social Reciprocity Scale). RESULTS: The results were consistent with the existence of a singular, continuously distributed underlying factor, resulting in disparate phenotypic manifestations across the three criterion domains for autistic disorder (social deficits, language deficits, and repetitive/stereotypic behaviors). CONCLUSION: The analyses generally failed to support the existence of independent sub domains of dysfunction in autism spectrum conditions. Future studies of the association between genetic/neurobiologic markers and autistic symptomatology may be enhanced by approaches which consider autistic symptoms as quantitative traits, and which are informed by ongoing research on the development and phenomenology of core deficiencies in reciprocal social behavior.

Adolescent↗

PubMed1998

Outcomes of genetic evaluation in children with pervasive developmental disorder.

We undertook a retrospective etiological study of all children referred for evaluation of pervasive developmental disorder (PDD). We identified 91 children who met the DSM III-R criteria for PDD. Fifty-two were diagnosed with autistic disorder (AD), and 39 with PDD-not otherwise specified (PDD-NOS). Seven families (8.2%) had more than one affected sib. The overall recurrence rate was 7.1%. Six families had a positive history of PDD in more distant relatives. An excess of developmental problems were identified on the maternal side (seven families, vs two families on the paternal side). Affected children had head circumferences above the mean when compared with standardized growth curves. A recognizable syndrome or genetic disorder was identified in 14 children (15.4%), of which 8 children (9%) were thought to be causative of PDD (5 children with Rett syndrome, 2 with fragile X syndrome, and 1 with velocardiofacial syndrome [VCFS]). Six others had a recognized genetic, cytogenetic, or metabolic disorder believed to be unrelated to the PDD diagnosis. Given the relatively high yield of genetic diagnoses in this population, we believe that children with PDD-NOS or AD should have a detailed evaluation by a clinical geneticist or pediatrician trained in dysmorphology. Chromosome anomalies, fragile X, and other recognizable disorders, including VCFS, need to be excluded. The value of general screening for an inborn error of metabolism in all children with PDD is not certain. In light of the relatively high recurrence of PDD in families, genetic counseling is recommended.

Adolescent↗

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↗

PubMed1996

Joint attention in preverbal children: autism and developmental language disorder.

For preverbal children, episodes of joint attention are contexts for communication with responsive adults. This study describes the joint attention of 3- to 5-year-old children, 15 with autistic disorder (AD) and 15 with developmental language disorder (DLD), during play sessions with unfamiliar adults. Adults used fewer conventional than literal bids for joint attention with AD children and vice versa with DLD children. Children with AD were less likely to engage in joint attention than children with DLD. In the allocation of attention, AD children monitored the channel of communication with the adult 37% less often than DLD children. We discuss how perturbations in reciprocal interactions permeate the sharing situation and the implications of this problem for the mastery of cultural conventions.

Attention↗

PubMedDate not supplied

Cerebrospinal fluid levels of homovanillic acid and 5-hydroxyindoleacetic acid in autism.

Cerebrospinal fluid (CSF) concentrations of the serotonin and dopamine metabolites, 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA), respectively, were measured in a group of 17 children with Autistic Disorder (DSM-III-R). The group means observed for 5HIAA (135 +/- 91 nmol/L) and HVA (502 +/- 324 nmol/L) in the autistic children were not significantly different from those seen in the control group of 15 nonneurologically impaired children (5HIAA, 122 +/- 120 nmol/L; HVA 401 +/- 378 nmol/L). These data suggest that consistent, marked alterations in central serotonin and dopamine turnover are not present in the autistic subjects studied. Although studies to date have found little or no alteration in CSF 5-HIAA in autism, the various reports of CSF HVA are not entirely congruent. Although this study is consistent with most previous studies in not finding a group difference in CSF HVA, the possibility of increased CSF HVA in autism cannot be ruled out.

Autistic Disorder↗

PubMed1990

Association of acrocyanosis with Asperger's syndrome.

The authors present three men with both acrocyanosis and Asperger's syndrome. Though the general incidence of acrocyanosis is unknown, they suggest that it is probably more common in autistic disorders and may be caused by hyperserotonaemia.

Adolescent↗

PubMedDate not supplied

[Early autism and congenital muscular dystrophy: a clinical case].

The authors describe the case of a twelve-year-old patient presenting early autism associated with congenital muscular dystrophy--subtype IV, according to the subclassification of Fukuyama (slight mental retardation, ability to walk, muscle pseudohypertrophy). To our knowledge, this association has never been reported. Several factors may have played a causative role in the development of an autistic disorder in the patient. The authors suggest the following as the most significant ones: disharmonious personality, weak emotional structure, inadequate primary relation with the mother, poor environmental influences, frustrations encountered because of the muscular disorder.

Autistic Disorder↗

PubMedDate not supplied

Specialized family care for children with developmental disabilities: the Finnish experience.

This article describes features of Finland's specialized family care for children with disabilities, including professionalization and training of foster parents and the establishment of municipal employee-like status for them, long-term placements, and the preservation of relationships with biological families whenever possible. A case example of a 12-year-old child with mental retardation and autistic disorder who is in specialized care is included.

Autistic Disorder↗

PubMed2006

Animal models relevant to schizophrenia and autism: validity and limitations.

Development of animal models is a crucial issue in biological psychiatry. Animal models provide the opportunity to decipher the relationships between the nervous system and behavior and they are an obligatory step for drug tests. Mouse models or rat models to a lesser extent could help to test for the implication of a gene using gene targeting or transfecting technologies. One of the main problem for the development of animal models is to define a marker of the psychiatric disorder. Several markers have been suggested for schizophrenia and autism, but for the moment no markers or etiopathogenic mechanisms have been identified for these disorders. We examined here animal models related to schizophrenia and autism and discussed their validity and limitations after first defining these two disorders and considering their similarities and differences. Animal models reviewed in this article test mainly behavioral dimensions or biological mechanisms related to autistic disorder or schizophrenia rather than providing specific categorical models of autism or schizophrenia. Furthermore, most of these studies focus on a behavioral dimension associated with an underlying biological mechanism, which does not correspond to the complexity of mental disorders. It could be useful to develop animal models relevant to schizophrenia or autism to test a behavioral profile associated with a biological profile. A multi-trait approach seems necessary to better understand multidimensional disorders such as schizophrenia and autism and their biological and clinical heterogeneity. Finally, animal models can help us to clarify complex mechanisms and to study relationships between biological and behavioral variables and their interactions with environmental factors. The main interest of animal models is to generate new pertinent hypotheses relevant to humans opening the path to innovative research.

Animals↗