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Electrocardiographic changes in children and adolescents treated with ziprasidone: a prospective study.

OBJECTIVE: To assess the electrocardiographic safety profile of low-dose ziprasidone (< or =40 mg/day) among pediatric outpatients treated for up to 6 months. METHOD: This was a prospective, open-label trial involving 20 subjects with a mean age of 13.2 +/- 3.0 years. Subjects received a mean ziprasidone dose of 30 +/- 13 mg/day and were followed for 4.6 +/- 2.0 months, receiving a median of nine electrocardiograms each (range 2-11; total, 176). RESULTS: There were statistically significant changes from baseline to peak values in heart rate, PR, and QTc intervals, but not in QRS complex width. The mean QTc prolongation was 28 +/- 26 milliseconds and not related to dose (r = 0.16, p = .07). The peak QTc of three subjects reached or exceeded 450 milliseconds; one subject experienced a 114-millisecond prolongation. There was poor agreement (kappa = 0.25) between automated and manual identification of long QTc intervals (> or =440 milliseconds). CONCLUSIONS: These preliminary findings, occurring at doses low by current treatment standards, suggest that close electrocardiographic monitoring is warranted when prescribing ziprasidone to children, particularly at higher doses or when combined with other QTc-prolonging agents.

Adolescent↗

Annotation: Hyperlexia: disability or superability?

BACKGROUND: Hyperlexia is the phenomenon of spontaneous and precocious mastery of single-word reading that has been of interest to clinicians and researchers since the beginning of the last century. METHODS: An extensive search of publications on the subject of hyperlexia was undertaken and all available publications were reviewed. RESULTS: The literature can be subdivided into discussions of the following issues: (1) whether hyperlexia is a phenomenon that is characteristic only of specific clinical populations (e.g., children with developmental delays) or whether it can also be observed in the general population; (2) whether hyperlexia is a distinct syndrome comorbid with a number of different disorders or whether it is a part of the spectrum of some other clinical condition(s); (3) whether hyperlexia should be defined through single-word reading superiority with regard to reading comprehension, vocabulary, general intelligence, any combination of the three, or all three characteristics; (4) whether there is a specific neuropsychological profile associated with hyperlexia; (5) whether hyperlexia is characterized by a particular developmental profile; and (6) whether hyperlexia should be viewed as a disability (deficit) or superability (talent). CONCLUSIONS: We interpret the literature as supporting the view that hyperlexia is a superability demonstrated by a very specific group of individuals with developmental disorders (defined through unexpected single-word reading in the context of otherwise suppressed intellectual functioning) rather than as a disability exhibited by a portion of the general population (defined through a discrepancy between levels of single-word reading and comprehension). We simultaneously argue, however, that multifaceted and multi-methodological approaches to studying the phenomenon of hyperlexia, defined within the research framework of understanding single-word reading, are warranted and encouraged.

Adolescent↗

The familial aggregation of the lesser variant in biological and nonbiological relatives of PDD probands: a family history study.

OBJECTIVE: To determine the risk of the lesser variant (or PDD-like traits) in the biological and nonbiological second- and third-degree relatives of PDD probands using a screening questionnaire and to investigate the extent to which the risk of the lesser variant differs according to various characteristics of the proband. METHOD: The sample consists of a series of 34 nuclear families with 2 affected PDD children (multiplex, MPX), 44 families with a single PDD child (simplex, SPX), and 14 families who adopted a PDD child. Data on characteristics of the lesser variant in 1362 biological and 337 nonbiological second- and third-degree relatives were collected from parents by telephone interview and from several maternal and paternal relatives by questionnaire. RESULTS: All components of the lesser variant were more common in biological relatives (BR) than nonbiological relatives (NBR), confirming the familial aggregation of the traits. Proband characteristics associated with an increased risk of the lesser variant in relatives were a higher level of functioning and coming from a MPX family. CONCLUSIONS: These findings on the familial aggregation of the lesser variant suggest that the genes for PDD also confer susceptibility to the lesser variant and that PDD may be a genetically heterogeneous disorder.

Adolescent↗

Computer-assisted linguistic analysis of an autistic adolescent's language: implications for the diagnosis of Aspberger's syndrome and atypical psychoses.

This study illustrates the use of a computer-assisted linguistic analysis technique to compare the spoken language of an adolescent, diagnosed in childhood as autistic, with that of normal and schizophrenic individuals. A distinctive profile, in keeping with accounts in the literature of autistic speech, was noted to be radically different from that found in linguistic analysis of schizophrenic speech. This distinctive profile was mirrored by her written linguistic analysis. Changes indicative of some improvement in language function were seen on re-recording after 5 years. Implications of this technique for differential diagnosis of Aspberger's syndrome and atypical psychoses are mentioned.

Adolescent↗

The use of clozapine in adults with intellectual disability.

BACKGROUND: There are not many studies on the use of clozapine in patients with intellectual disability (ID). The authors describe a case series of patients treated with clozapine, drawn from a medium secure unit, a low secure assessment and treatment service and a community team in the London region. METHOD: A retrospective file-review of patients treated in these three settings during the time period March-June 2002 was performed (n = 24). Information was collected using a semistructured proforma. RESULTS: Of the 24 patients, 67% had schizophrenia, 17% had schizoaffective disorder and 8% had bipolar disorder. Patients had been unwell for a mean of 6 years and had been tried on a mean of four antipsychotics. The mean maximum dose of clozapine was 488 mg. The outcomes on the clinical global impression (CGI) scale showed 29% very much improved, 42% much improved, 21% minimally improved and 8% no change. 54% of the whole sample and 53% of those from the medium secure unit were discharged to homes in the community. The drug had to be stopped in four patients, of which three were because of neutropaenia. CONCLUSION: Clozapine appears to be safe and efficacious in many people with ID. Careful monitoring of side-effects is needed during therapy.

Adult↗

Disintegrative disorder or "late onset" autism.

Ten cases of disintegrative disorder were identified within a larger sample of 165 individuals who met behavioral criteria for autism. These cases were compared to autistic individuals whose disorder had been recognized by age 2 and to those whose disorder had been recognized after age 2. Consistent with previous reports, children with disintegrative disorder had a period of normal development preceding the onset of a profound developmental regression from which they made, at best, only a limited recovery. Both clinical features at the time of regression and various outcome measures support the validity of the diagnostic concept, particularly when such cases are compared to "late onset" autistic ones.

Adolescent↗

The epidemiology of Asperger syndrome. A total population study.

This paper describes a total population study of Asperger syndrome using a two-stage procedure. All school children in an outer Göteborg borough were screened. Final case selection based on clinical work-up showed a minimum prevalence of 3.6 per 1.000 children (7-16 years of age) using Gillberg and Gillberg's criteria and a male to female ratio of 4:1. Including suspected and possible Asperger syndrome cases, the prevalence rose to 7.1 per 1.000 children and the male:female ratio dropped to 2.3:1. These findings are discussed as they relate to previously published results in the field and to findings obtained using Szatmari et al.'s and ICD-10 draft criteria for the disorder.

Adolescent↗

Disembedding performance and recognition memory in autism/PDD.

This study explored the claim that superior disembedding performance in autism reflects "less capture by meaning" and/or reduced "central coherence" [Shah & Frith, Journal of Child Psychology & Psychiatry, 24, 613-620 (1983); Shah & Frith, Journal of Child Psychology & Psychiatry, 34, 1351-1364 (1993)]. Meaningless as well as meaningful disembedding contexts were used, and memory for contextual information was examined. Neither qualitative (search strategy) nor quantitative (RT or accuracy) data indicated that high-functioning individuals with autism/PDD were superior to younger, developmentally matched controls. For both groups, disembedding was slowest from meaningful contexts, which generally were remembered best. No evidence was provided for "less capture by meaning" or reduced "central coherence" in autism/PDD, raising the possibility that earlier findings reflect a developmental, rather than a stable autism-specific, phenomenon.

Adolescent↗

Another advanced test of theory of mind: evidence from very high functioning adults with autism or asperger syndrome.

Previous studies have found a subgroup of people with autism or Asperger Syndrome who pass second-order tests of theory of mind. However, such tests have a ceiling in developmental terms corresponding to a mental age of about 6 years. It is therefore impossible to say if such individuals are intact or impaired in their theory of mind skills. We report the performance of very high functioning adults with autism or Asperger Syndrome on an adult test of theory of mind ability. The task involved inferring the mental state of a person just from the information in photographs of a person's eyes. Relative to age-matched normal controls and a clinical control group (adults with Tourette Syndrome), the group with autism and Asperger Syndrome were significantly impaired on this task. The autism and Asperger Syndrome sample was also impaired on Happé's strange stories tasks. In contrast, they were unimpaired on two control tasks: recognising gender from the eye region of the face, and recognising basic emotions from the whole face. This provides evidence for subtle mindreading deficits in very high functioning individuals on the autistic continuum.

Adolescent↗

Mind-reading difficulties in the siblings of people with Asperger's syndrome: evidence for a genetic influence in the abnormal development of a specific cognitive domain.

BACKGROUND: Previous research suggests that the phenotype associated with Asperger's syndrome (AS) includes difficulties in understanding the mental states of others, leading to difficulties in social communication and social relationships. It has also been suggested that the first-degree relatives of those with AS can demonstrate similar difficulties, albeit to a lesser extent. This study examined 'theory of mind' (ToM) abilities in the siblings of children with AS relative to a matched control group. METHOD: 27 children who had a sibling with AS were administered the children's version of the 'Eyes Test' (Baron-Cohen, Wheelwright, Stone, & Rutherford, 1999). The control group consisted of 27 children matched for age, sex, and a measure of verbal comprehension, and who did not have a family history of AS/autism. RESULTS: A significant difference was found between the groups on the Eyes Test, the 'siblings' group showing a poorer performance on this measure of social cognition. The difference was more pronounced among female siblings. DISCUSSION: These results are discussed in terms of the familial distribution of a neuro-cognitive profile associated with AS, which confers varying degrees of social handicap amongst first-degree relatives. The implication of this finding with regard to the autism/AS phenotype is explored, with some discussion of why this neuro-cognitive profile (in combination with corresponding strengths) may have an evolutionary imperative.

Adolescent↗

Annotation: what do we know about sensory dysfunction in autism? A critical review of the empirical evidence.

BACKGROUND: Unusual responses to sensory stimuli are seen in many children with autism. Their presence was highlighted both in early accounts of autism and in more recent first-person descriptions. There is a widespread belief that sensory symptoms characterize autism and differentiate it from other disorders. This paper examines the empirical evidence for this assumption. METHOD: All controlled experimental laboratory investigations published since 1960 were identified through systematic searches using Medline/PubMed and PsycInfo search engines. A total of 48 empirical papers and 27 theoretical or conceptual papers were reviewed. RESULTS: Sensory symptoms are more frequent and prominent in children with autism than in typically developing children, but there is not good evidence that these symptoms differentiate autism from other developmental disorders. Certain groups, including children with fragile X syndrome and those who are deaf-blind, appear to demonstrate higher rates of sensory symptoms than children with autism. In reviewing the evidence relevant to two theories of sensory dysfunction in autism, over- and under-arousal theory, we find that there is very little support for hyper-arousal and failure of habituation in autism. There is more evidence that children with autism, as a group, are hypo-responsive to sensory stimuli, but there are also multiple failures to replicate findings and studies that demonstrate lack of group differences. CONCLUSIONS: The use of different methods, the study of different sensory modalities, and the changing scientific standards across decades complicate interpretation of this body of work. We close with suggestions for future research in this area.

Arousal↗