1. Carroll LS, Owen MJ. {{Genetic overlap between autism, schizophrenia and bipolar disorder}}. {Genome Med};2009 (Oct 30);1(10):102.
ABSTRACT: There is strong evidence that genetic factors make substantial contributions to the etiology of autism, schizophrenia and bipolar disorders, with heritability estimates being at least 80% for each. These illnesses have complex inheritance, with multiple genetic and environmental factors influencing disease risk; however, in psychiatry, complex genetics is further compounded by phenotypic complexity. Autism, schizophrenia and bipolar disorder are effectively syndromic constellations of symptoms that define groups of patients with broadly similar outcomes and responses to treatment. As such the diagnostic categories are likely to be heterogeneous and the boundaries between them somewhat arbitrary. Recent applications of whole-genome technologies have discovered rare copy number variants and common single-nucleotide polymorphisms that are associated with risk of developing these disorders. Furthermore, these studies have shown an overlap between the genetic loci and even alleles that predispose to the different phenotypes. The findings have several implications. First, they show that copy number variations are likely to be important risk factors for autism and schizophrenia, whereas common single-nucleotide polymorphism alleles have a role in all disorders. Second, they imply that there are specific genetic loci and alleles that increase an individual’s risk of developing any of these disorders. Finally, the findings suggest that some of the specific genetic loci implicated so far encode proteins, such as neurexins and neuroligins, that function in synaptic development and plasticity, and therefore may represent a common biological pathway for these disorders.
2. Dichter GS, Radonovich KJ, Turner-Brown LM, Lam KS, Holtzclaw TN, Bodfish JW. {{Performance of Children with Autism Spectrum Disorders on the Dimension-Change Card Sort Task}}. {J Autism Dev Disord};2009 (Nov 5)
Restricted and repetitive behaviors in autism spectrum disorders have been conceptualized to reflect impaired executive functions. In the present study, we investigated the performance of 6-17-year-old children with and without an autism spectrum disorder on a dimension-change card sort task that explicitly indicated sorting rules on every trial. Diagnostic groups did not differ in speed of responses after the first rule switch or in speed or accuracy on blocks with mixed versus single sort rules. However, performance of the ASD group was significantly slower and less accurate overall than the typically-developing group. Furthermore, within the ASD group, poorer DCCS task performance did not predict more severe autism symptoms. Implications for the executive dysfunction theory of autism are discussed.
3. Hobson RP, Garcia-Perez RM, Lee A. {{Person-Centred (Deictic) Expressions and Autism}}. {J Autism Dev Disord};2009 (Nov 3)
We employed semi-structured tests to determine whether children with autism produce and comprehend deictic (person-centred) expressions such as ‘this’/’that’, ‘here’/’there’ and ‘come’/’go’, and whether they understand atypical non-verbal gestural deixis in the form of directed head-nods to indicate location. In Study 1, most participants spontaneously produced deictic terms, often in conjunction with pointing. Yet only among children with autism were there participants who referred to a location that was distal to themselves with the terms ‘this’ or ‘here’, or made atypical points with unusual precision, often lining-up with an eye. In Study 2, participants with autism were less accurate in responding to instructions involving contrastive deictic terms, and fewer responded accurately to indicative head nods.
4. Kates WR, Ikuta I, Burnette CP. {{Gyrification patterns in monozygotic twin pairs varying in discordance for autism}}. {Autism Res};2009 (Nov 3)
In order to disentangle genetic and environmental contributions to cortical anomalies in children with autism, we investigated cortical folding patterns in a cohort of 14 monozygotic (MZ) twin pairs who displayed a range of phenotypic discordance for autism, and 14 typically developing community controls. Cortical folding was assessed with the gyrification index, which was calculated on high resolution anatomic MR images. We found that the cortical folding patterns across most lobar regions of the cerebral cortex was highly discordant within MZ twin pairs. In addition, children with autism and their co-twins exhibited increased cortical folding in the right parietal lobe, relative to age- and gender-matched typical developing children. Increased folding in the right parietal lobe was associated with more symptoms of autism for co-twins. Finally, the robust association between cortical folding and IQ observed in typical children was not observed in either children with autism or their co-twins. These findings, which contribute to our understanding of the limits of genetic liability in autism, suggest that anomalies in the structural integrity of the cortex in this PDD may disrupt the association between cortical folding and intelligence that has been reported in typical individuals, and may account, in part, for the deficits in visual spatial attention and in social cognition that have been reported in children with autism.
5. Koldewyn K, Whitney D, Rivera SM. {{The psychophysics of visual motion and global form processing in autism}}. {Brain};2009 (Nov 3)
Several groups have recently reported that people with autism may suffer from a deficit in visual motion processing and proposed that these deficits may be related to a general dorsal stream dysfunction. In order to test the dorsal stream deficit hypothesis, we investigated coherent and biological motion perception as well as coherent form perception in a group of adolescents with autism and a group of age-matched typically developing controls. If the dorsal stream hypothesis were true, we would expect to document deficits in both coherent and biological motion processing in this group but find no deficit in coherent form perception. Using the method of constant stimuli and standard psychophysical analysis techniques, we measured thresholds for coherent motion, biological motion and coherent form. We found that adolescents with autism showed reduced sensitivity to both coherent and biological motion but performed as well as age-matched controls during coherent form perception. Correlations between intelligence quotient and task performance, however, appear to drive much of the group difference in coherent motion perception. Differences between groups on coherent motion perception did not remain significant when intelligence quotient was controlled for, but group differences in biological motion perception were more robust, remaining significant even when intelligence quotient differences were accounted for. Additionally, aspects of task performance on the biological motion perception task were related to autism symptomatology. These results do not support a general dorsal stream dysfunction in adolescents with autism but provide evidence of a more complex impairment in higher-level dynamic attentional processes.
6. Mouridsen SE, Rich B, Isager T. {{A longitudinal study of gastrointestinal diseases in individuals diagnosed with infantile autism as children}}. {Child Care Health Dev};2009 (Nov 2)
Abstract Background A number of studies have indicated a link between gastrointestinal (GI) diseases and autism spectrum disorders. Method The objective of this study was to compare the prevalence and types of GI diseases in a clinical sample of 118 individuals diagnosed as children with infantile autism (IA) with GI diseases in 336 matched controls from the general population, based on data from the nationwide Danish National Hospital Register (DNHR). The average observation time was 30.3 years (SD 0.4) (range 27-30 years), and mean age at the end of the observation period was 42.7 years (SD 7.7) (range between 27 and 57 years of age). Results Of the 118 individuals with IA, 97 (82.2%) had been in contact with a medical hospital (inpatient hospitalization or outpatient visits) during the observation period, compared with 312/336 (92.9%) in the control group (P= 0.001). A similar proportion of members from the case and comparison group had a diagnosis of any GI disease in the DNHR: 30.5% against 30.7%, but the nature of their diseases may be somewhat different. Only diseases of oral cavity were significantly associated with IA: 20.3% against 1.2%, P < 0.0001. Otherwise, specific GI diseases occurred with low frequency in both groups. Conclusion Overall, no evidence was found that patients with IA were more likely than control persons without IA to have defined GI diseases during the 30.3-year observation period.
7. Nishiyama T, Notohara M, Sumi S, Takami S, Kishino H. {{Major contribution of dominant inheritance to autism spectrum disorders (ASDs) in population-based families}}. {J Hum Genet};2009 (Nov 6)
Results of twin studies have shown that autism spectrum disorders (ASDs) are attributable to complex multigenic interactions rather than to a single susceptibility gene. However, the growing number of distinct, individually rare genetic causes of ASDs, mostly copy number variations (CNVs), favors an alternative to the polygenic hypothesis, the two-component model, which suggests that ASDs are caused either by de novo mutation or by dominant inheritance from asymptomatic carriers of such a mutation. To verify this hypothesis, we estimated the distribution of ASD-risk among both catchment area-based families and multiplex families. Our results suggest that the models with more than three risk components are preferable to the two-component model. Our results also suggest that the largest proportion of ASD cases is caused by dominant inheritance. We additionally show that Supplementary information regarding prevalence has a crucial role in analyzing proband-ascertained data.Journal of Human Genetics advance online publication, 6 November 2009; doi:10.1038/jhg.2009.105.
8. Sheppard E, Ropar D, Underwood G, van Loon E. {{Brief Report: Driving Hazard Perception in Autism}}. {J Autism Dev Disord};2009 (Nov 5)
This study investigated whether individuals with ASD (autistic spectrum disorders) are able to identify driving hazards, given their difficulties processing social information, Klin et al. (Archives of General Psychiatry 59: 809-816, 2002). Twenty-three adult males with ASD and 21 comparison participants viewed 10 video clips containing driving hazards. In half of the clips the source of the hazard was a visible person (social); in the other half the source was a car (non-social). Participants with ASD identified fewer social hazards than the comparison participants (U = 163.00, N = 44, p < .05) but not non-social. Participants with ASD were also slower to respond than comparison participants, F(1,40) = 4.93, p < .05. This suggests that, although people with ASD can perceive driving hazards they may have specific difficulty identifying them if they involve a person.
9. Skokauskas N, Gallagher L. Psychosis, {{Affective Disorders and Anxiety in Autistic Spectrum Disorder: Prevalence and Nosological Considerations}}. {Psychopathology};2009 (Nov 6);43(1):8-16.
Background: This review aimed to find relevant published studies on the co-morbidity of autism and Asperger’s syndrome with psychotic, anxiety and/or mood disorders, assess them, synthesize the findings, present an overview and make recommendations for future research. Methods: Systematic literature searches were performed using several databases. Selected articles had to describe an original study that provided prevalence and/or incidence estimates on autism and/or Asperger’s syndrome co-morbidity with psychotic, anxiety and/or mood disorders. Results and Conclusion: There is conflicting evidence regarding the frequency of schizophrenia in this population. Depression appears to be common, although most individuals with autism do not have sufficient language skills to verbalize changes in mood. Anxiety disorders represent the most common psychiatric co-morbidity in this population.
10. Taurines R, Thome J, Duvigneau JC, Forbes-Robertson S, Yang L, Klampfl K, Romanos J, Muller S, Gerlach M, Mehler-Wex C. {{Expression analyses of the mitochondrial complex I 75-kDa subunit in early onset schizophrenia and autism spectrum disorder: increased levels as a potential biomarker for early onset schizophrenia}}. {Eur Child Adolesc Psychiatry};2009 (Nov 6)
Searching for a peripheral biological marker for schizophrenia, we previously reported on elevated mitochondrial complex I 75-kDa subunit mRNA-blood concentrations in early onset schizophrenia (EOS). The aim of this study was to further evaluate the utility of this gene as a potential marker for schizophrenia. Both-schizophrenia and autism-are suggested to be neuronal maldevelopmental disorders with reports of mitochondrial dysfunction and increased oxidative stress. Therefore we have investigated the expression levels of mitochondrial complex I 75-kDa subunit mRNA in whole blood of children with autistic spectrum disorder (ASD) and a group of adolescent acute first-episode EOS patients in comparison to matched controls. We have found that compared to the respective controls only the group of EOS patients-and not the ASD group-showed a significantly altered expression of the complex I 75-kDa subunit mRNA. Although further studies are necessary to test for the specificity of this marker, our findings point to the potential use of the mitochondrial complex I as a biomarker for schizophrenia.
11. Toal F, Daly EM, Page L, Deeley Q, Hallahan B, Bloemen O, Cutter WJ, Brammer MJ, Curran S, Robertson D, Murphy C, Murphy KC, Murphy DG. {{Clinical and anatomical heterogeneity in autistic spectrum disorder: a structural MRI study}}. {Psychol Med};2009 (Nov 6):1-11.
BACKGROUND: Autistic spectrum disorder (ASD) is characterized by stereotyped/obsessional behaviours and social and communicative deficits. However, there is significant variability in the clinical phenotype; for example, people with autism exhibit language delay whereas those with Asperger syndrome do not. It remains unclear whether localized differences in brain anatomy are associated with variation in the clinical phenotype.MethodWe used voxel-based morphometry (VBM) to investigate brain anatomy in adults with ASD. We included 65 adults diagnosed with ASD (39 with Asperger syndrome and 26 with autism) and 33 controls who did not differ significantly in age or gender. RESULTS: VBM revealed that subjects with ASD had a significant reduction in grey-matter volume of medial temporal, fusiform and cerebellar regions, and in white matter of the brainstem and cerebellar regions. Furthermore, within the subjects with ASD, brain anatomy varied with clinical phenotype. Those with autism demonstrated an increase in grey matter in frontal and temporal lobe regions that was not present in those with Asperger syndrome. CONCLUSIONS: Adults with ASD have significant differences from controls in the anatomy of brain regions implicated in behaviours characterizing the disorder, and this differs according to clinical subtype.
