[Executive function deficits in ADHD and Asperger syndrome]. / Deficit delle funzioni esecutive nell'ADHD e nella sindrome di Asperger.

BACKGROUND: The aim of this study is to evaluate the executive functioning of children with attention deficit hyperactivity disorder combined subtype (ADHD-C) and Asperger syndrome (AS) compared to a control group. METHODS: A sample of 79 children (28 ADHD-C; 24 AS; 27 subjects with typical development) was tested on a wide range of tasks related to major domains of executive functioning: inhibition response (prepotent and interference), visual working memory, planning and cognitive flexibility. RESULTS: Patients with AS showed deficits on visual working memory and cognitive flexibility. ADHD-C children were impaired on inhibition control (prepotent response) but also showed deficits on working memory and cognitive flexibility. The only executive functioning measure that differentiated ADHD from AS was inhibition of prepotent response and a more high deficit in cognitive flexibility and working memory in AS compared to ADHD-C. CONCLUSIONS: This study confirms recent evidence about the identification of specific executive profiles in these disorders. Other studies are warranted to evaluate the presence and specifity of a dysexecutive syndrome in ADHD and AS in a larger sample with girls.

Assessing attentional systems in children with Attention Deficit Hyperactivity Disorder.

The aim of this study was to evaluate the efficiency and interactions of attentional systems in children with Attention Deficit Hyperactivity Disorder (ADHD) by considering the effects of reinforcement and auditory warning on each component of attention. Thirty-six drug-naïve children (18 children with ADHD/18 typically developing children) performed two revised versions of the Attentional Network Test, which assess the efficiency of alerting, orienting, and executive systems. In feedback trials, children received feedback about their accuracy, whereas in the no-feedback trials, feedback was not given. In both conditions, children with ADHD performed more slowly than did typically developing children. They also showed impairments in the ability to disengage attention and in executive functioning, which improved when alertness was increased by administering the auditory warning. The performance of the attentional networks appeared to be modulated by the absence or the presence of reinforcement. We suggest that the observed executive system deficit in children with ADHD could depend on their low level of arousal rather than being an independent disorder.

The neurobiology of attention deficit/hyperactivity disorder.

ADHD is a brain based disorder with structural and functional abnormalities in widespread but specific areas of the brain. The most significant and consistent structural imaging findings include smaller total brain volumes, and reduced volumes in the right frontal lobe, right parietal cortex, caudate nucleus, cerebellar hemispheres, and posterior-inferior lobules of the cerebellar vermis. ADHD involves hypofunction of catecholaminergic circuits, particularly those that project to the prefrontal cortex. A minimum of 18 genes have been reported to be associated with the disorder; among them the DRD4 7-repeat allele has been found associated with a thinner prefrontal and posterior parietal cortex. Epigenetic factors acting during critical periods of prenatal and postnatal development may interact with genetic determinants. Methylphenidate, as well as the catecholaminergic nonstimulant atomoxetine, are effective in improving ADHD symptoms.

Attention and executive functions profile in drug naive ADHD subtypes.

Attention deficit hyperactivity disorder (ADHD) has been associated with executive functioning and sustained and divided attention deficits. In order to clarify the questions on neurocognitive impairment in ADHD, we investigated the presence of specific executive functions (EFs) and attention deficit patterns in ADHD clinical subtypes. 50 patients with ADHD and 44 controls were evaluated. All subjects were boys and performed a clinical-psychopathological and neuropsychological battery. Five main domains of EFs and attention were studied. Executive functions-related neurocognitive abilities were used as control tasks. ADHD patients, inattentive and combined subtypes differ from controls on response inhibition, divided attention, phonological, and visual object working memory and on variability of reaction times measured with CPT. Comparison of ADHD subtypes, in five main domains of EFs, did not show evidence of different executive functioning profiles. Response inhibition can predict performance on working memory tests but it cannot predict performance on divided attention/set shifting and on sustained attention. ADHD boys exhibit a selective impairment on executive functions and attention tasks. These data suggest the involvement of partially independent neural circuits which control inhibition and divided attention in ADHD. Since right prefrontal cortex seems to be crucial in controlling response inhibition, while left dorsolateral prefrontal cortex seems important in modulating divided attention, these areas are deputated to be involved in the pathogenesis of neuropsychological deficits in ADHD subtypes. In addition, this study candidates the impairment in phonological and visual-object working memory as a possible neuropsychological trait in ADHD males with inattentive or combined subtypes.

Mutations of the Nogo-66 receptor (RTN4R) gene in schizophrenia.

Schizophrenia (SCZD) or schizoaffective disorders are quite common features in patients with DiGeorge/velo-cardio-facial syndrome (DGS/VCFS) as a result of chromosome 22q11.2 aploinsufficiency. We evaluated the Nogo-66 receptor gene (RTN4R), which maps within the DGS/VCFS critical region, as a potential candidate for schizophrenia susceptibility. RTN4R encodes for a functional cell surface receptor, a glycosylphosphatidylinositol (GPI)-linked protein, with multiple leucine-rich repeats (LRR), which is implicated in axonal growth inhibition. One hundred and twenty unrelated Italian schizophrenic patients were screened for mutations in the RTN4R gene using denaturing high performance liquid chromatography (DHPLC). Three mutant alleles were detected, including two missense changes (c.355C>T; R119W and c.587G>A; R196H), and one synonymous codon variant (c.54G>A; L18L). The two schizophrenic patients with the missense changes were strongly resistant to the neuroleptic treatment at any dosage. Both missense changes were absent in 300 control subjects. Molecular modeling revealed that both changes lead to putative structural alterations of the native protein.