Marie-Hélène Plumet

Towards a Cognitive Phenotype for Autism: Increased Prevalence of Executive Dysfunction and Superior Spatial Span amongst Siblings of Children with Autism

Two studies were conducted to examine executive function skills in siblings of children with autism. In Study 1, four computerised tasks (three executive tasks: the ID/ED set-shifting task; a spatial working memory task; and the Tower of London planning task; and a control spatial span task) from the CANTAB battery were used to compare 31 siblings of children with autism with 32 siblings of children with developmental delay and 32 children from unaffected families. In Study 2, the two sibling groups were compared on two manually administered executive tasks (verbal fluency and list recall). As a group, autism siblings showed superior spatial and verbal span, but a greater than expected number performed poorly on the set-shifting, planning, and verbal fluency tasks. There were no group differences in working memory performance. The implications of these findings for the broader phenotype of autism is discussed.

Low-dose naltrexone effects on plasma chemistries and clinical symptoms in autism: a double-blind, placebo-controlled study

The effect of month-long naltrexone (NTX) treatment at a daily oral dose of 0.5 mg/kg/day was contrasted with placebo (PLC) in a double-blind study with conjoint clinical and biochemical evaluations of therapeutic effects. Modest clinical benefits were achieved with both PLC and NTX, with marginally better overall results following NTX, and degree of improvement appeared to be related to plasma chemical profiles. Massively elevated levels of beta-endorphin were observed in all children with assays using C-terminal antibody but not with an N-terminal antibody assay. In addition, 70% of the children exhibited abnormally low levels of adrenocorticotropic hormone, and smaller subsets exhibited elevated norepinephrine (60%), arginine-vasopressin (50%), and serotonin (20%). The best clinical responders exhibited the clearest normalization of the elevated plasma chemistries, especially in C-terminal-beta-endorphin and serotonin. There was some evidence of therapeutic carry-over effects in both clinical and biochemical measures in those children who received NTX before PLC. The results suggest that NTX only benefits a subgroup of autistic children, who may be identified by the presence of certain plasma abnormalities. These results suggest a possible linkage between abnormal plasma chemistries, especially those related to the pro-opiomelanocortin system, and autistic symptoms.

Executive function and theory of mind in school-aged children after neonatal corrective cardiac surgery for transposition of the great arteries

Aim  Cardiac malformations resulting in cyanosis, such as transposition of the great arteries (TGA), have been associated with neurodevelopmental dysfunction. The purpose of this study was to assess, for the first time, theory of mind (ToM), which is a key component of social cognition and executive functions in school‐aged children with TGA.

Impact of prenatal diagnosis on neurocognitive outcomes in children with transposition of the great arteries.

OBJECTIVES To assess the effect of prenatal diagnosis of congenital heart disease on neurocognitive outcomes in children with d-transposition of the great arteries (TGA) after surgical correction. STUDY DESIGN A prospective study of children born with a TGA between 2003 and 2005 and aged 4 to 6 years was conducted. General intelligence, language, executive functions, and social cognition scores and preoperative, intraoperative, and postoperative factors were evaluated according to time of TGA diagnosis. Neurocognitive data were also compared with a control group. RESULTS Forty-five eligible patients (67% male) were examined; 29 had a prenatal diagnosis of TGA and 16 did not. All children were comparable in age, sex, and demographic variables. Diagnostic groups did not differ in preoperative, intraoperative, and postoperative variables. Preoperative acidosis was more frequent in the postnatal group (18% versus 3%). All patients had normal IQ scores, language, and verbal working memory. However, neurocognitive deficits were more prevalent and more severe in children with a postnatal-TGA. Prenatal diagnosis was associated with better outcomes in executive functions. CONCLUSIONS Prenatal diagnosis of TGA is associated with better neurocognitive outcomes. Time of diagnosis may influence the development of early complex cognitive skills such as executive functions.

Micro-analysis of social interactions between autistic children and normal adults in semi-structured play situations

The present study was designed to: (1) identify the qualitative and temporal characteristics of the exchange structures of autistic children interacting with an adult; and (2) analyse and compare the implementation of their interactive behaviour in a range of play situations. Ten autistic children aged 5 to 14 were video-taped while interacting with an adult in four play situations, with or without objects. The elementary behavioural events observed in the dyads were coded and processed on a computer by an automatic pattern detection program. The results showed that in this structured situation the autistic children engaged in a variety of behaviours for communicating with the adult, and that 8 of the 10 children repeatedly exhibited structures of interaction. These patterns were found to depend on IQ, but involved a certain number of peculiar characteristics (parasitic behaviours, lack of initiative, maladapted visual behaviour, etc.), even for the children with the highest IQ scores. The physical interaction situations gave rise to fewer and less elaborate patterns than the situations involving objects. Only the most advanced children participated in the joint-attention situation. The implications of the method for understanding the abnormal development of interaction in autism are discussed.

Verbal Skills in Relatives of Autistic Females

First-degree relatives of 26 autistic females and 26 Downs syndrome females were tested on a battery of verbal tasks designed to detect subtle anomalies. No differences were found when comparing parents of the two groups, but there was a significant difference between siblings. This result was accounted for by a lower performance of the brothers of autistic subjects. The verbal scores of the relatives, either parents or siblings, were not related to the IQ of the proband. Findings are discussed in relation to the hypothesis of genetic and/or environmental factors in autism.

Fringe phenotypes in autism: a review of clinical, biochemical and cognitive studies

Progress in identifying the genetic vulnerability factors in autism requires correct identification of the inherited phenotype(s). This can be achieved not only by the accurate description of the affected subject but also by the identification of vulnerability traits in non-affected relatives of autistic probands. This review will focus on this last strategy and principally on clinical, biochemical and cognitive traits.

Verbal versus visuospatial abilities in relatives of autistic females

Parents and siblings of 26 autistic females and 26 Downs syndrome females were compared on a battery of verbal and visuospatial tasks to test the possibility of familial aggregation of a particular cognitive profile. No difference was found between parents of both groups. In contrast, siblings of autistic females showed significantly lower verbal abilities than controls but did not differ in their visuospatial performance. This difference appeared attributable to brothers of autistic females, some of whom showed an especially pronounced discrepant profile at the disadvantage of verbal abilities compared to their visuospatial abilities. Results are discussed in terms of genetic and/or environ mental factors that may account for an aggregation of cognitive features ranging from left‐hemisphere impairments to enhanced right‐hemisphere abilities.