1. Anney RJ, Lasky-Su J, O’Dushlaine C, Kenny E, Neale BM, Mulligan A, Franke B, Zhou K, Chen W, Christiansen H, Arias-Vasquez A, Banaschewski T, Buitelaar J, Ebstein R, Miranda A, Mulas F, Oades RD, Roeyers H, Rothenberger A, Sergeant J, Sonuga-Barke E, Steinhausen H, Asherson P, Faraone SV, Gill M. {{Conduct disorder and ADHD: Evaluation of conduct problems as a categorical and quantitative trait in the international multicentre ADHD genetics study}}. {Am J Med Genet B Neuropsychiatr Genet};2008 (Dec 5);147B(8):1369-1378.
Attention-deficit/hyperactivity disorder (ADHD) is typically characterized by inattention, excessive motor activity, impulsivity, and distractibility. Individuals with ADHD have significant impairment in family and peer relations, academic functioning, and show high co-morbidity with a wide range of psychiatric disorders including oppositional defiant disorder (ODD), conduct disorder (CD), anxiety disorder, depression, substance abuse, and pervasive developmental disorder (PDD). Family studies suggest that ADHD + CD represents a specific subtype of the ADHD disorder with familial risk factors only partly overlapping with those of ADHD alone. We performed a hypothesis-free analysis of the GAIN-ADHD sample to identify markers and genes important in the development of conduct problems in a European cohort of individuals with ADHD. Using the Family-Based Association Test (FBAT) package we examined three measures of conduct problems in 1,043,963 autosomal markers. This study is part of a series of exploratory analyses to identify candidate genes that may be important in ADHD and ADHD-related traits, such as conduct problems. We did not find genome-wide statistical significance (P < 5 x 10(-7)) for any of the tested markers and the three conduct problem traits. Fifty-four markers reached strong GWA signals (P < 10(-5)). We discuss these findings in the context of putative candidate genes and the implications of these findings in the understanding of the etiology of ADHD + CD. We aimed to achieve insight into the genetic etiology of a trait using a hypothesis-free study design and were able to identify a number of biologically interesting markers and genes for follow-up studies. (c) 2008 Wiley-Liss, Inc.
2. Bolte S, Dziobek I, Poustka F. {{Brief Report: The Level and Nature of Autistic Intelligence Revisited}}. {J Autism Dev Disord};2008 (Dec 4)
Owing to higher performance on the Raven’s Progressive Matrices (RPM) than on the Wechsler Intelligence Scales (WIS), it has recently been argued that intelligence is underestimated in autism. This study examined RPM and WIS IQs in 48 individuals with autism, a mixed clinical (n = 28) and a neurotypical (n = 25) control group. Average RPM IQ was higher than WIS IQ only in the autism group, albeit to a much lesser degree than previously reported and only for individuals with WIS IQs <85. Consequently, and given the importance of reliable multidimensional IQ estimates in autism, the WIS are recommended as first choice IQ measure in high functioning individuals. Additional testing with the RPM might be required in the lower end of the spectrum.
3. Geier DA, Kern JK, Garver CR, Adams JB, Audhya T, Geier MR. A {{Prospective Study of Transsulfuration Biomarkers in Autistic Disorders}}. {Neurochem Res};2008 (Dec 5)
4. Meilleur AA, Fombonne E. {{Regression of language and non-language skills in pervasive developmental disorders}}. {J Intellect Disabil Res};2008 (Nov 27)
Abstract Background As part of the pervasive developmental disorders (PDD), there is a subgroup of individuals reported to have a different onset of symptom appearance consisting of an apparently normal early development, followed by a loss of verbal and/or non-verbal skills prior to 2 years of age. This study aims at comparing the symptomatology of children who displayed a regression and often an associated intellectual disability through investigation of two types of loss, namely language and other skill regression. Methods This study examined the occurrence of regression in 135 children with PDD, mean age 6.3 years. The sample was composed of 80 (59.4%) children diagnosed with autism, 44 (32.6%) with pervasive developmental disorder-not otherwise specified (PDD-NOS) and 11 (8%) with Asperger syndrome. The Autism Diagnostic Interview Revised (ADI-R) was used to evaluate the type of loss and to characterise associated factors including birth rank, gender and thimerosal exposure through vaccination. Results A total of 30 (22%) subjects regressed: nine (30%) underwent language regression alone, 17 (57%) lost a skill other than language and four (13%) lost both language and another skill. Significantly higher levels of regression were found in autism (30%) compared with PDD-NOS (14%) and Asperger syndrome (0%). Children who regressed in language skills spoke at a significantly earlier age ( = 12 months) than those who did not regress in this domain ( = 26 months). Parents and interviewers consistently reported developmental abnormalities prior to the loss. ADI-R domain mean scores indicated a more severe autistic symptomatology profile in children who regressed compared with those who did not, especially in the repetitive behaviour domain. Regression was not associated to thimerosal exposure, indirectly estimated by year of birth. Conclusions A loss of skill, present in one out of five children with PDD, is associated with a slightly more severe symptomatology as measured by the ADI-R, particularly in the repetitive behaviours domain. Furthermore, although abnormalities are often noticed by the caregivers at the time of regression, the ADI-R reveals that other atypical behaviours were in fact present prior to the onset of regression in most cases. None of the secondary factors investigated were associated with regression. In children unexposed to thimerosal-containing vaccines, the rate of regression was similar to that reported in studies of samples exposed to thimerosal, suggesting that thimerosal has no specific association with regressive autism.
5. Pijnacker J, Hagoort P, Buitelaar J, Teunisse JP, Geurts B. {{Pragmatic Inferences in High-Functioning Adults with Autism and Asperger Syndrome}}. {J Autism Dev Disord};2008 (Dec 4)
Although people with autism spectrum disorders (ASD) often have severe problems with pragmatic aspects of language, little is known about their pragmatic reasoning. We carried out a behavioral study on high-functioning adults with autistic disorder (n = 11) and Asperger syndrome (n = 17) and matched controls (n = 28) to investigate whether they are capable of deriving scalar implicatures, which are generally considered to be pragmatic inferences. Participants were presented with underinformative sentences like « Some sparrows are birds ». This sentence is logically true, but pragmatically inappropriate if the scalar implicature « Not all sparrows are birds » is derived. The present findings indicate that the combined ASD group was just as likely as controls to derive scalar implicatures, yet there was a difference between participants with autistic disorder and Asperger syndrome, suggesting a potential differentiation between these disorders in pragmatic reasoning. Moreover, our results suggest that verbal intelligence is a constraint for task performance in autistic disorder but not in Asperger syndrome.
6. Roux JC, Dura E, Villard L.{{ Tyrosine hydroxylase deficit in the chemoafferent and the sympathoadrenergic pathways of the Mecp2 deficient mouse}}. {Neurosci Lett};2008 (Dec 5);447(1):82-86.
Mutations in the gene encoding the transcriptional methyl-CpG binding protein 2 (Mecp2) cause a wide range of neurological disorders and the better known of these diseases is Rett syndrome (RS). Mecp2 deficiency has been previously associated to catecholaminergic dysfunction in the mouse brainstem. Here we report a catecholaminergic deficit in the peripheral nervous system of the Mecp2-/y males and heterozygous Mecp2+/- female mice. We used immunoquantification associated to densitometry to evaluate the amount of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis, in the key organs of the chemoafferent and sympathoadrenergic pathways: the carotid body (CB), the petrosal ganglion (PG), the superior cervical ganglion (SCG) and the adrenal medulla (AM). Our results show that the TH staining level is weaker in the CB (-15%), PG (-26%), SCG (-34%), AM (-35%) of Mecp2-/y mice and to a lesser extent in the PG (-11%) and AM (-18%) in Mecp2+/- mice. We evaluated in vivo the chemoreflex sensitivity of Mecp2-/y mice using whole-body plethysmography to record the breathing of Mecp2-/y mice in normoxia and in response to acute hypoxia (10% O(2)). Our results show that the hypoxic ventilatory response is significantly increased in Mecp2-/y mice (+50%) demonstrating in vivo disturbances of the chemoafferent pathway. In conclusion, our results offer new insights to better understand the mechanisms leading to autonomic dysfunction in RS.
7. Stefanatou A. {{Use of drawings in children with pervasive developmental disorder during hospitalization: a developmental perspective}}. {J Child Health Care};2008 (Dec);12(4):268-283.
The level and nature of emotional upheaval and relationship to developmental stage was studied in children with pervasive developmental disorder (PDD) hospitalized for head injury. The sample consisted of 25 hospitalized children aged 5-12 years. Children were asked to make the drawing of a ;person in hospital’. The drawings were evaluated by Koppitz’s emotional indicators. Punishment and persecution were the main cognitive constructs of children in order to explain hospitalization.
8. Steinlin M. {{Cerebellar Disorders in Childhood: Cognitive Problems}}. {Cerebellum};2008 (Dec 5)
Over the last decade, increasing evidence of cognitive functions of the cerebellum during development and learning processes could be ascertained. Posterior fossa malformations such as cerebellar hypoplasia or Joubert syndrome are known to be related to developmental problems in a marked to moderate extent. More detailed analyses reveal special deficits in attention, processing speed, visuospatial functions, and language. A study about Dandy Walker syndrome states a relationship of abnormalities in vermis lobulation with developmental problems. Further lobulation or volume abnormalities of the cerebellum and/or vermis can be detected in disorders as fragile X syndrome, Downs’s syndrome, William’s syndrome, and autism. Neuropsychological studies reveal a relation of dyslexia and attention deficit disorder with cerebellar functions. These functional studies are supported by structural abnormalities in neuroimaging in these disorders. Acquired cerebellar or vermis atrophy was found in groups of children with developmental problems such as prenatal alcohol exposure or extreme prematurity. Also, focal lesions during childhood or adolescence such as cerebellar tumor or stroke are related with neuropsychological abnormalities, which are most pronounced in visuospatial, language, and memory functions. In addition, cerebellar atrophy was shown to be a bad prognostic factor considering cognitive outcome in children after brain trauma and leukemia. In ataxia teleangiectasia, a neurodegenerative disorder affecting primarily the cerebellar cortex, a reduced verbal intelligence quotient and problems of judgment of duration are a hint of the importance of the cerebellum in cognition. In conclusion, the cerebellum seems to play an important role in many higher cognitive functions, especially in learning. There is a suggestion that the earlier the incorrect influence, the more pronounced the problems.
