Philippe Robaey

Perceptual Processing among High-functioning Persons with Autism

Two tasks were used to assess the processing of whole versus parts of objects in a group of high-functioning children and adolescents with autism (N = 11) and a comparison group of typically developing peers (N = 11) matched for chronological age and IQ. In the first task, only the children with autism showed a global advantage, and the two groups showed similar interference between levels. In the second task, the children with autism, despite longer RTs, showed similar performance to the comparison group with regard to the effect of goodness on visual parsing. Contrary to expectations based on the central coherence and hierarchisation deficit theories, these findings indicate intact holistic processing among persons with autism. The implications of these findings are discussed in relation to apparently discrepant evidence from other studies.

Mediators of behavioral problems in 7-year-old children born after 24 to 28 weeks of gestation

We tested the hypothesis that prematurity acts through its association with neuromotor and intellectual functioning to explain behavior problems at school age. Sixty-one extremely preterm (EP) very low birth weight (VLBW) children (< 29 wk and < 1500 g) born in 1987-1990 and 44 normal birth weight children (NBW) (> 37 wk and > 2500 g) were matched for age, sex, and socioeconomic status (SES). Mediator variables were evaluated at a hospital at 5 years and 9 months. Behaviors were evaluated at school at 7 years by peers, teachers, and parents. When compared with NBW children, EP/VLBW children had poorer IQ and neuromotor development. At school, EP/VLBW children were evaluated by peers as more sensitive/isolated, and by teachers and parents as more inattentive and hyperactive than NBW. When mediators were introduced, the previously significant relation between prematurity and behavior problems disappeared. Hyperactive and inattentive behaviors were explained by a specific working memory factor for the latter, and by a general intellectual delay for the former, whereas sensitive/isolated behaviors were best explained by neuromotor delays. Inattentive behaviors were also related to family adversity. At school age, extreme prematurity had thus an indirect effect on behaviors via specific and nonspecific intellectual and neuromotor delays.

Neuropsychological Outcomes From a Randomized Trial of Triple Intrathecal Chemotherapy Compared With 18 Gy Cranial Radiation As CNS Treatment in Acute Lymphoblastic Leukemia: Findings From Dana-Farber Cancer Institute ALL Consortium Protocol 95-01

PURPOSE We evaluated late neuropsychological toxicity in children treated for standard-risk acute lymphoblastic leukemia (ALL) who were randomly assigned to receive either cranial radiation therapy (CRT) with double intrathecal (IT) chemotherapy or intensive triple IT chemotherapy (no CRT) as CNS-directed therapy. PATIENTS AND METHODS Between 1996 and 2000, 164 children with standard-risk ALL treated on Dana-Farber Cancer Institute Consortium Protocol 95-01 were randomly assigned to receive either 18 Gy CRT delivered in twice daily fractions (0.9 [DOSAGE ERROR CORRECTED] Gy) with double IT therapy (methotrexate and cytarabine) or intensive triple IT drug (methotrexate, cytarabine and hydrocortisone) without CRT. Neuropsychological testing was completed at a median 6 years postdiagnosis for 79 children (CRT, n = 39; triple IT, n = 40), all of whom were in continuous complete remission. RESULTS Cognitive function for both groups was solidly in the average range, with no consistent group differences in basic cognitive skills. Children treated on the CRT plus double IT arm did, however, exhibit less fluent output and were less effective at modulating their behavior by parent report. CONCLUSION This randomized trial revealed only subtle differences 6 years after diagnosis between children who received CNS therapy as CRT plus double IT drug or as intensive triple IT drug. In most situations where comparable therapeutic efficacy can be achieved without CRT, it is preferable to do so. Where therapeutically necessary, however, CRT at lower doses may not add risk for significant neurotoxicity.

Virtual navigation strategies from childhood to senescence: evidence for changes across the life span

This study sought to investigate navigational strategies across the life span, by testing 8-years old children to 80-years old healthy older adults on the 4 on 8 virtual maze (4/8VM). The 4/8VM was previously developed to assess spontaneous navigational strategies, i.e., hippocampal-dependent spatial strategies (navigation by memorizing relationships between landmarks) versus caudate nucleus-dependent response strategies (memorizing a series of left and right turns from a given starting position). With the 4/8VM, we previously demonstrated greater fMRI activity and gray matter in the hippocampus of spatial learners relative to response learners. A sample of 599 healthy participants was tested in the current study. Results showed that 84.4% of children, 46.3% of young adults, and 39.3% of older adults spontaneously used spatial strategies (p < 0.0001). Our results suggest that while children predominantly use spatial strategies, the proportion of participants using spatial strategies decreases across the life span, in favor of response strategies. Factors promoting response strategies include repetition, reward and stress. Since response strategies can result from successful repetition of a behavioral pattern, we propose that the increase in response strategies is a biological adaptive mechanism that allows for the automatization of behavior such as walking in order to free up hippocampal-dependent resources. However, the down-side of this shift from spatial to response strategies occurs if people stop building novel relationships, which occurs with repetition and routine, and thereby stop stimulating their hippocampus. Reduced fMRI activity and gray matter in the hippocampus were shown to correlate with cognitive deficits in normal aging. Therefore, these results have important implications regarding factors involved in healthy and successful aging.

Adrenocortical Functioning in Boys with Attention-Deficit/Hyperactivity Disorder: Examining Subtypes of ADHD and Associated Comorbid Conditions

Disruptions to hypothalamic-pituitary-adrenal (HPA) axis function have been associated with varying forms of psychopathology in children. Studies suggesting children with ADHD have blunted HPA function have been complicated by the prevalence of comorbid diagnoses and heterogeneity of ADHD. The goals of this research were to assess the relations between waking and stress–response salivary cortisol levels and comorbid disruptive behavior (DBD) and anxiety (AnxD) disorders and problems in boys with ADHD, and to examine whether cortisol levels varied across ADHD subtypes. One hundred seventy elementary school-age boys with ADHD provided salivary cortisol at waking and in reaction to venipuncture. Parent reports were used to assess boys’ psychiatric diagnoses and severity of behavioral problems. Boys’ comorbid AnxD and anxiety problems were associated with greater cortisol reactivity, whereas boys’ comorbid DBD and oppositional problems predicted diminished adrenocortical activity. Reactive cortisol increases were greatest in boys with ADHD and comorbid AnxD, but without DBD. ADHD subtypes were not differentially associated with waking, pre-stress baseline, or reactive cortisol levels. However, comorbid DBD predicted decreased cortisol reactivity in boys with inattentive and hyperactive subtypes of ADHD, but not in boys with combined subtype of ADHD. The results clarify previous patterns of distinct and divergent dysregulations of HPA function associated with boys’ varying kinds of psychopathology.

The Quebec Newborn Twin Study Into Adolescence: 15 Years Later

The Quebec Newborn Twin Study (QNTS) is an ongoing prospective longitudinal follow-up of a birth cohort of twins born between 1995 and 1998 in the greater Montreal area, Québec, Canada. The goal of QNTS is to document individual differences in the cognitive, behavioral, and social-emotional aspects of developmental health across childhood, their early bio-social determinants, as well as their putative role in later social-emotional adjustment, school and health outcomes. A total of 662 families of twins were initially assessed when the twins were aged 6 months. These twins and their family were then followed regularly. QNTS has 14 waves of data collected or planned, including 5 in preschool. Over the past 15 years, a broad range of physiological, cognitive, behavioral, school, and health phenotypes were documented longitudinally through multi-informant and multi-method measurements. QNTS also entails extended and detailed multi-level assessments of proximal (e.g., parenting behaviors, peer relationships) and distal (e.g., family income) features of the childs environment. This detailed longitudinal information makes QNTS uniquely suited for the study of the role of the early years and gene-environment transactions in development.

Victimization: a newly recognized outcome of prematurity

Victimization by peers affects 10 to 20% of school children under the age of 12 years. Physical, verbal, and psychological victimization (being pushed, hit, called names, teased, being the target of rumours, theft, extortion) is associated with short‐ and long‐term adjustment problems, such as peer rejection, social withdrawal, low self‐esteem, anxiety, loneliness, and depression, as well as academic problems and school drop‐out. Research on populations of school children (primary and secondary) has associated victimization with personal risk factors (the victims characteristics and behaviour) and interpersonal risk factors (social relationships between peers). Studies on the social adjustment of preterm children at school age show that, even in the absence of a major motor or cognitive disability, this population has several personal risk factors associated with victimization. The objective of this study was to compare the level of victimization experienced by a group of 96 seven‐year‐old children born extremely preterm (EP, <29 weeks of gestation; 49 females) against that experienced by a group of 63 term children (34 females) matched for age and sex, maternal level of education, and family socioeconomic status. The children born EP had a mean gestational age of 27.3 weeks (SD 1.2) and a mean birthweight of 1001.1g (SD 223) and normal birth weight children had a mean gestational age of 39.5 weeks (SD 1.5) and a mean birthweight of 3468.7g (SD 431). Physical and verbal victimization were assessed in a school setting by peers with individual sociometric interviews (Modified Peer Nomination Inventory). After controlling for physical growth (height and weight) at the age of 7 years, the data indicate two independent effects: males were more victimized than females, and children born preterm experienced more verbal victimization by their peers than their term classmates, even when participants with a visible motor, intellectual, or sensory disability were excluded. Several hypotheses are presented to account for the higher incidence of verbal victimization of preterm children.

Polymorphisms of genes controlling homocysteine levels and IQ score following the treatment for childhood ALL

INTRODUCTION One of the causes of long-term morbidity associated with the treatment of acute lymphoblastic leukemia (ALL) is late neurotoxicity manifesting as impairment of higher cognitive functions. Cranial radiation therapy (CRT) and chemotherapeutic agents, particularly methotrexate (MTX), are often suggested to be major contributing factors for its development. Homocysteinemia that arises as a result of MTX-induced folate depletion was proposed to play a role in MTX-related neurotoxicity. Several enzymes are essential to maintain the homocysteine levels. Their different functional forms, associated with common genetic polymorphisms, may modulate homocysteine levels and thereby influence MTX-associated neurotoxicity. OBJECTIVES To test this hypothesis we assessed whether the variants of the methylene tetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), cystathionine beta-synthase (CBS) and endothelial nitric acid synthase (eNOS, NOS3) genes, acting either independently or in conjunction with other risk factors, influenced the cognitive functioning in ALL patients. The influence of the genes was measured by estimating the change in IQ scores over a period of 4 years post ALL diagnosis. RESULTS Two variants, the CBS 844ins68 polymorphism and NOS3 894T homozygosity, were associated with a change in IQ scores (p = 0.01 and 0.007, respectively). A multivariate model obtained through step-wise selection pointed to the importance of the NOS3 894TT genotype only. This effect appears to be dependent on CRT; IQ decline was apparent among individuals with the 894TT genotype who received radiation therapy (p = 0.03). Furthermore, additional factors affecting IQ were identified, including the treatment administered (i.e., CRT; p = 0.02) and a younger age at diagnosis (p = 0.003), and the modifying effect of the treatment protocols was also noted (p = 0.04). CONCLUSION The results suggest that NOS3 genotyping might identify individuals that are susceptible to intellectual impairment following ALL treatment.

Posttraumatic Stress Symptoms and Medical Procedures in Children

Objective: To focus on posttraumatic stress symptoms after childhood diseases such as cancer, organ transplantation, and severe burns. Methods: Differential diagnoses, risk factors, and treatment aspects (psychological and pharmacological) are discussed. Results: The concept of adjustment problems in chronic or severe illnesses is widely used in pediatrics. Many aspects of severe childhood diseases are traumatic, as defined by the DSM-IV: severe illnesses are life-threatening, medical procedures threaten the childs physical integrity, and disorganized behaviour periods are common. Conclusion: This concept, which remains insufficiently investigated, is a promising area of investigation for prospective and prevention studies.

Verbal Cognitive Functioning and Learning in Girls Treated for Acute Lymphoblastic Leukemia By Chemotherapy With or Without Cranial Irradiation

Neuropsychological problems have frequently been reported following treatment of Acute Lymphoblastic Leukemia (ALL), however, partly because of the heterogeneity of the previously studied samples, the specific nature of these deficits is still a matter of debate. These problems, however, appear to be related more to the combination of cranial radiation therapy (CRT) and intrathecal chemotherapy (ITC) than to ITC alone. In this study, we evaluated a homogenous group of l9 girls between the ages of 7 and 11 years, 30 months after the completion of treatment. Nine received cranial radiation and chemotherapy and 10 were treated with chemotherapy alone. The patients were compared to 10 normal healthy controls. Neuropsychological tests included the Wechsler Intelligence Scale for Children-Third Edition (WISC-III), the California Verbal Learning Test-Childrens Version (CVLT-C), and the Calculation and Passage Comprehension subtests of the Woodcock-Johnson Psycho-Educational Battery-Revised. Results confirmed the presence of a verbal learning deficit in ALL girls treated with the combination of ITC and CRT. The ITC and CRT group scored significantly lower than the healthy controls on the Passage Comprehension subtest and on 5 of the 6 verbal subtests of the WISC-III. Furthermore, compared to nonirradiated patients and healthy normal controls, the ITC and CRT group was impaired on the Freedom from Distractibility index of the WISC-III, indicating an auditory-verbal attention deficit. On the CVLT-C, the ITC and CRT group was particularly impaired on the second half of the learning trials compared to the other two groups, showing a plateau in their performance. The ITC group was not different from the healthy control group, suggesting a less detrimental effect of the ITC alone on verbal abilities. Globally, these results indicate a deficit affecting auditory attention and verbal learning in girls who receive ITC and CRT, which may suggest the necessity for special educational assistance for these children.