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Of five patients with pervasive developmental disorders (PDDs), four developed psychotic illnesses in adult life. The other was treated with antipsychotic medication for many years following a mistaken diagnosis of schizophrenia.
OBJECTIVE: Pediatric populations, including those with autistic disorder or other pervasive developmental disorders, increasingly are being prescribed selective serotonin reuptake inhibitors (SSRIs). Little is known about the age-related brain pharmacokinetics of SSRIs; there is a lack of data regarding optimal dosing of medications for children. The authors used fluorine magnetic resonance spectroscopy ((19)F MRS) to evaluate age effects on whole-brain concentrations of fluvoxamine and fluoxetine in children taking SSRIs. METHOD: Twenty-one pediatric subjects with diagnoses of autistic disorder or other pervasive developmental disorders, 6-15 years old and stabilized with a consistent dose of fluvoxamine or fluoxetine, were recruited for the study; 16 successfully completed the imaging protocol. Whole-brain drug levels in this group were compared to similarly acquired data from 28 adults. RESULTS: A significant relationship between dose and brain drug concentration was observed for both drugs across the age range studied. Brain fluvoxamine concentration in the children was lower, consistent with a lower dose/body mass drug prescription; when brain concentration was adjusted for dose/mass, age effects were no longer significant. Brain fluoxetine concentration was similar between age groups; no significant age effects on brain fluoxetine drug levels remained after adjustment for dose/mass. Observations of brain fluoxetine bioavailability and elimination half-life also were similar between age groups. CONCLUSIONS: These findings suggest that fluvoxamine or fluoxetine prescriptions adjusted for dose/mass are an acceptable treatment approach for medicating children with autistic disorder or other pervasive developmental disorders. It must be determined whether these findings can be generalized to other pediatric populations.
A systematic review of randomized controlled trials of the use of atypical antipsychotics and selective serotonin reuptake inhibitors in the treatment of behavioural problems associated with pervasive developmental disorders is reported. A search through both published and unpublished literature, including contacting drug companies and known experts in the field was undertaken. Six trials met the criteria for inclusion in the review. They largely suffer from methodological weaknesses; only two trials had satisfactory methodological quality. The heterogeneity in outcome measurements prevented from conducting a meta-analysis. There is yet no coherent body of data concerning the effects of these medications across all sub-classifications of pervasive developmental disorders, across all age categories, and concerning their medium- and long-term effects, and their effects on quality of life. Atypical antipsychotics and selective serotonin reuptake inhibitors may be of benefit for behavioural problems associated with pervasive developmental disorders. Risperidone has been the best studied among these medications. Atypical antipsychotics appear to have a low risk of extrapyramidal symptoms during short-term treatment. The reviewed trials cannot provide data on the use of selective serotonin reuptake inhibitors in the treatment of children with pervasive developmental disorders. No firm conclusions for clinical practice can be drawn. Larger, well-conducted randomized controlled trials with long-term follow-up are needed.
BACKGROUND: Autistic disorder (AD) is a disabling oligogenic condition characterized by severe social impairment. Subthreshold autistic social impairments are known to aggregate in the family members of autistic probands; therefore, we conducted this study to examine the intergenerational transmission of such traits in the general population. METHODS: The Social Responsiveness Scale (SRS), a quantitative measure of autistic traits, was completed on 285 pairs of twins (by maternal report) and on their parents (by spouse report). RESULTS: Correlation for social impairment or competence between parents and their children and between spouses was on the order of .4. In families in which both parents scored in the upper quartile for social impairment on the SRS, mean SRS score of offspring was significantly elevated (effect size 1.5). Estimated assortative mating explained approximately 30% of the variation in parent SRS scores. CONCLUSIONS: Children from families in which both parents manifest subthreshold autistic traits exhibit a substantial shift in the distribution of their scores for impairment in reciprocal social behavior, toward the pathological end. As has been previously demonstrated in children, heritable subthreshold autistic impairments are measurable in adults and appear continuously distributed in the general population.
Children with arrested, shunted, and no hydrocephalus were compared on verbal and nonverbal memory tasks assessing multiple components of memory. A gradient of severity was hypothesized, with the shunted hydrocephalus group expected to exhibit the most significant memory impairments and the arrested group expected to perform more poorly than children with no hydrocephalus. Etiologies of prematurity, spina bifida, and aqueductal stenosis were represented by 157 participants. Results supported the hypothesis; the shunted hydrocephalus group performed poorer on all memory measures. Differences for the arrested group were less frequently statistically significant relative to children with no hydrocephalus. Irrespective of etiology, the shunted hydrocephalus group exhibited a pattern of performance suggestive of encoding and retrieval deficits on both verbal and nonverbal tasks, showing a pervasive disturbance of memory processes.
We conducted a 12-year prospective study of children with pervasive developmental disorders from North Dakota. In a prospective longitudinal follow-up study, of 59 patients, we found 52 patients with pervasive developmental disorders (88%). Ten (17%) declined to participate. We collected data on 42 (71%) of the original cohort. Of the 42 subjects, 1 died (1.7%). The other 41 were followed up for 492 person-years. Severity scores for the Diagnostic and Statistical Manual of Mental Disorders-III-Revised (DSM-III-R) declined 20% and for DSM-IV 23%. Global Assessment of Functioning improved 19%, and the average number of comorbidities decreased 45%. Thirty-seven percent of patients improved in all four measures, whereas only 5% improved in only one measure. Pervasive developmental disorders are developmental disorders with a long-term course of limited improvement for most patients. Male subjects demonstrated substantially more variability in improvement but, overall, demonstrated more improvement than female subjects.
Prader-Willi syndrome (PWS), a genetic form of mental retardation, involves a myriad of physical and behavioral problems. Poor social adjustment has been reported, but the origin of this difficulty is unknown. The Social Attribution Task, a measure of one's ability to make appropriate social attributions from an ambiguous visual display [Klin (2000) Journal of Child Psychology and Psychiatry, 33(5) [861-876] was administered to study participants with PWS, participants with pervasive developmental disorder and an IQ matched comparison group with no known syndrome. The participants with PWS performed significantly more poorly than participants with comparable intellectual ability, and not significantly differently from the group of participants with a pervasive developmental disorder. Poor performance on this task by the PWS participants suggests an underlying difficulty interpreting social information that is presented visually, which may be a critical factor in the impairment in social functioning in this population.
The American Psychiatric Association's last version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; APA, 1994) identifies within pervasive developmental disorders five subgroups: (a) autistic disorder; (b) Rett's disorder; (c) childhood disintegrative disorder; (d) Asperger's disorder's and (e) pervasive developmental disorder not otherwise specified. However, the diagnosis of the different sub-groups is difficult to establish, particularly between autistic disorder and Asperger's disorder. This article exposes the diagnostic criteria of autism and Asperger's syndrome in order to illustrate the similarities and differences between the two disorders.
This article describes the method and results of a national field trial of the proposed criteria for the DSM-III-R diagnosis of autistic disorder at 11 sites which have experience in diagnosing pervasive developmental disorders. Using the diagnosis of autistic disorder made by expert clinicians as a standard, the diagnostic criteria that were finally included in DSM-III-R demonstrated high sensitivity and specificity across different age groups and in children with and without language.
This is a case report of a 15-year-old visually impaired, mentally retarded male who presents with symptoms consistent with Tourette Syndrome, a Syndrome of approximate answers (Ganser's Syndrome) and Atypical Pervasive Developmental Disorder. The authors feel that this follow-up on the case presented earlier by Parraga and Butterfield raises the possibility of a link between a number of the symptoms of adult schizophrenia, appearing in attenuated form in these two cases, and Tourette Syndrome.
The cerebellum is involved in motor and cognitive functions and behavior. Its role in controlling epileptic seizures has been demonstrated in the literature. Genetic factors can enhance epilepsy susceptibility when the cerebellum is damaged. We examined the occurrence and features of epilepsy, intelligence, and psychiatric disorders in 28 patients with cerebellar hypoplasia. We compared patients with (10; 35.7%) and without (18; 64.3%) epilepsy. The statistical evaluation showed a significant prevalence of familial antecedents for seizures in patients with epilepsy (P < .01); cerebral associated lesions and type of cerebellar hypoplasia did not influence the occurrence of epilepsy, which was partial in 80% of cases. Profound mental retardation prevailed in patients with epilepsy (P < .05). Both mental retardation (75%) and pervasive developmental disorders (17.8%) prevailed in our cases with respect to the general population (P < .000). Cerebellar hypoplasia in our sample seems to be an important risk factor for the occurrence of epilepsy, mental retardation, and psychiatric disorders.
OBJECTIVE: To investigate the short-term safety and efficacy of risperidone in the treatment of children and adolescents with pervasive developmental disorders. METHOD: This was a 12-week, prospective, systematic, open-label trial that included 18 subjects (15 boys and 3 girls) with a mean age of 10.2 +/- 3.7 years. The sample included 11 subjects with autistic disorder, 3 with Asperger's disorder, 1 with childhood disintegrative disorder, and 3 with pervasive developmental disorder not otherwise specified. Fourteen subjects had comorbid mental retardation. Behavioral ratings were obtained during two baseline visits and again after 12 weeks of risperidone treatment. RESULTS: The optimal dose of risperidone for the 18 subjects was 1.8 +/- 1.0 mg/day. On the basis of the global improvement item of the Clinical Global Impression Scale, 12 of 18 subjects were considered responders. Significant improvement was seen in measures of interfering repetitive behavior, aggression and impulsivity, and some elements of impaired social relatedness. The most common side effect was weight gain (range 10 to 35 lb). CONCLUSIONS: These preliminary results suggest that risperidone may be effective for improving interfering behavioral symptoms in some children and adolescents with pervasive developmental disorders. Double-blind, placebo-controlled studies are needed before definitive statements of safety and efficacy can be made.
OBJECTIVE: This project focused on the development of the definition of autism for DSM-IV. METHOD: Multiple sites were involved in obtaining information regarding 977 patients with the following clinician-assigned diagnoses: autism (N = 454), other pervasive developmental disorders (N = 240), and other disorders (N = 283). A standard coding system was used, and the raters (N = 125) had a range of experience in the diagnosis of autism. Patterns of agreement among existing diagnostic systems were examined, as was the rationale for inclusion of other disorders within the class of pervasive developmental disorders. RESULTS: The DSM-III-R definition of autism was found to be overly broad. The proposed ICD-10 definition most closely approximated the clinicians' diagnoses. Inclusion of other disorders within pervasive developmental disorders appeared justified. Partly on the basis of these data, modifications in the ICD-10 definition were made; this and the DSM-IV definition are conceptually identical. CONCLUSIONS: The resulting convergence of the DSM-IV and ICD-10 systems should facilitate both research and clinical service.
The purpose of exchange and development therapies (EDT) is to reduce the behavioural problems which are the expression of psychophysiological dysfunction. The aim of this study was to reveal the most disturbed psychophysiological functions and their evolution during the course of EDT in 42 children divided into three groups; group I--15 children with pure autism (A); group II--16 children with autism associated with neurological disorders (AA); and group III--11 children with pervasive developmental disorders (PDD). Among the 12 functions analysed, groups AA, A and APDD had respectively 8, 6 and 4 functions in which the score was high (> 2.5), indicating serious disorders (maximum 4). All the dysfunctions improved during EDT. However, each group had certain areas which were more susceptible to treatment. Further analysis of behaviour problems led to a more precise definition of the objectives and to the adaptation of the therapeutic methods to obtain greater effectiveness.
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.
BACKGROUND: Autism is considered to have a genetic basis, although exposure to certain stimuli in the prenatal period has been implicated to be causal in some cases. Some investigations have shown an association with obstetric complications but findings have been inconsistent owing to differences in sampling and methods. OBJECTIVE: To examine the association of obstetric factors with autism spectrum disorders for a cohort of children, using obstetric data contained in a statutory database collected at the time of birth. DESIGN: Subjects born in Western Australia between 1980 and 1995 and diagnosed with an autism spectrum disorder by 1999 were included as cases (n = 465). Siblings of the cases (n = 481) and a random population-based control group (n = 1313) were compared with the cases on obstetric information contained in the Maternal and Child Health Research Database of Western Australia. RESULTS: Compared with control subjects, cases had significantly older parents and were more likely to be firstborn. Case mothers had greater frequencies of threatened abortion, epidural caudal anesthesia use, labor induction, and a labor duration of less than 1 hour. Cases were more likely to have experienced fetal distress, been delivered by an elective or emergency cesarean section, and had an Apgar score of less than 6 at 1 minute. Cases with a diagnosis of autism had more complications than those with pervasive developmental disorder not otherwise specified or Asperger syndrome. Nonaffected siblings of cases were more similar to cases than control subjects in their profile of complications. CONCLUSIONS: Autism is unlikely to be caused by a single obstetric factor. The increased prevalence of obstetric complications among autism cases is most likely due to the underlying genetic factors or an interaction of these factors with the environment.
Genetic epidemiology is the study of inherited factors involved in the etiology of a disease or disorder and uses the methods of both medical genetics and clinical epidemiology. In general, genetic epidemiology tries to answer the following four questions: Is the disorder inherited; What phenotype is inherited; How is it inherited or what is the mode of transmission; and What is the nature of the genetic mutation, if any, that gives rise to the disorder? The hope is that by identifying the gene or genes involved in pathophysiology, a much better understanding of the steps from gene product to phenotype will be possible, leading to improvements in diagnosis, an opportunity for thoughtful family planning, and perhaps, most important, to the development of treatments based on an understanding of the biochemistry of the disorder. We review the current knowledge of the genetic epidemiology of autism and the other pervasive developmental disorders (PDDs) and highlight promising new directions. There seems to be widespread agreement that the PDDs are caused, at least in part, by genetic factors. There is also some agreement on the phenotypic boundaries associated with these same genetic factors. However, many points of uncertainty remain, and several methodologic issues need to be resolved before further progress in mapping susceptibility genes is possible. We do not specifically review molecular studies, medical conditions associated with autism, or the broader autism phenotype, as these topics are covered in other papers in this special issue.
This case study describes the association of Pseudologia Fantastica (PF) and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) in a 14-year-old girl. PF is seen in a number of diagnostic entities, but has not previously been reported in PDD spectrum disorders. Treatment implications are discussed along with a formulation of the psychological and cognitive functions of PF in a person with a PDD diagnosis.