Executive functions and memory abilities in children with 22q11.2 deletion syndrome.

OBJECTIVE: Velo-cardio-facial syndrome or 22q11.2 deletion syndrome (22q11DS) is the most common known microdeletion syndrome. One of the genes in the deleted region is the catechol-O-methyltransferase (COMT) gene, which is thought to have significant effects on cognition through its influence on dopamine metabolism. The aim of the present study was to better characterize the cognitive phenotype in a large cohort children with 22q11DS compared with sibling controls and to investigate if the cognitive deficits in 22q11DS were modulated by COMT expression. METHOD: The memory, executive function and attentional abilities of children with 22q11DS (n = 50) compared to sibling controls (n = 31), were measured. Also, within children with 22q11DS, a preliminary exploration was carried out of the relationship between cognitive ability and COMT genotype. RESULTS: Overall, the 22q11DS group had significantly reduced scores on tests of memory (especially in visual memory) and executive function (particularly in planning, working memory, and motor organization) compared with sibling controls. No association, however, was identified between COMT genotype and cognitive function. CONCLUSIONS: Although 22q11DS children have specific cognitive deficits, differences in COMT do not account for these findings.

Executive functioning differences between adults with attention deficit hyperactivity disorder and autistic spectrum disorder in initiation, planning and strategy formation.

Executive functioning deficits characterize the neuropsychological profiles of the childhood neurodevelopmental disorders of attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD). This study sought to determine whether similar impairments exist in adults with ADHD (N = 53) and ASD (N = 45) in comparison with a healthy control group (N = 31), whether the two disorders can be distinguished on the basis of their executive functioning features, and whether these impairments are related to symptom severity. Both clinical groups were found to exhibit executive functioning deficits. The ADHD group had difficulty withholding a response, with relative preservation of initiation and planning abilities. In contrast, the ASD group exhibited significant impairments in initiation, planning and strategy formation. The specific executive functioning deficits were related to severity of response inhibition impairments in ADHD and stereotyped, repetitive behaviours in ASD. These findings suggest the pattern of executive functioning deficits follows a consistent trajectory into adulthood.

In vivo 1H-magnetic resonance spectroscopy study of amygdala-hippocampal and parietal regions in autism.

OBJECTIVE: The neural basis for autistic spectrum disorders is unclear, but abnormalities in the development of limbic areas and of glutamate have been suggested. Proton magnetic resonance spectroscopy ((1)H-MRS) can be used to measure the concentration of brain metabolites. However, the concentration of glutamate/glutamine in brain regions implicated in autistic spectrum disorders has not yet been examined in vivo. METHOD: The authors used (1)H-MRS to investigate the neuronal integrity of the amygdala-hippocampal complex and a parietal control region in adults with autistic spectrum disorders and healthy subjects. RESULTS: People with autistic spectrum disorders had a significantly higher concentration of glutamate/glutamine and creatine/phosphocreatine in the amygdala-hippocampal region but not in the parietal region. CONCLUSIONS: Abnormalities in glutamate/glutamine may partially underpin the pathophysiology of autistic spectrum disorders, and the authors confirm earlier reports that limbic areas are metabolically aberrant in these disorders.

Neuropsychological functioning in adults with Asperger syndrome.

There is some consensus in the literature regarding the cognitive profile of people with Asperger syndrome (AS). Findings to date suggest that a proportion of people with AS have higher verbal than performance IQ, a non-verbal learning disability (NVLD) and impairments in some aspects of executive function (EF). However, there are few published studies on adults with AS and many have compared the AS group to an autistic control group alone. We compared cognitive functioning in 27 AS adults without a history of language delay and 20 normal controls who did not differ significantly in age, gender and IQ. People with AS had significant impairments on a test of visual memory and on EF tasks measuring flexibility and generativity, but not inhibition. There was no significant difference between verbal and performance IQ. Our results suggest that impairments on tests requiring flexibility of thought and generation occur at all ages and across a range of autistic disorders including AS.

Visuospatial working memory in children and adolescents with 22q11.2 deletion syndrome; an fMRI study.

22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with a microdeletion of chromosome 22q11. In addition to high rates of neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder, children with 22q11DS have a specific neuropsychological profile with particular deficits in visuospatial and working memory. However, the neurobiological substrate underlying these deficits is poorly understood. We investigated brain function during a visuospatial working memory (SWM) task in eight children with 22q11DS and 13 healthy controls, using fMRI. Both groups showed task-related activation in dorsolateral prefrontal cortex (DLPFC) and bilateral parietal association cortices. Controls activated parietal and occipital regions significantly more than those with 22q11DS but there was no significant between-group difference in DLPFC. In addition, while controls had a significant age-related increase in the activation of posterior brain regions and an age-related decrease in anterior regions, the 22q11DS children showed the opposite pattern. Genetically determined differences in the development of specific brain systems may underpin the cognitive deficits in 22q11DS, and may contribute to the later development of neuropsychiatric disorders.