1. Downs JA, Bebbington A, Jacoby P, Msall ME, McIlroy O, Fyfe S, Bahi-Buisson N, Kaufmann WE, Leonard H. {{Gross motor profile in rett syndrome as determined by video analysis}}. {Neuropediatrics};2008 (Aug);39(4):205-210.
Movement impairment is a fundamental but variable component of the Rett syndrome phenotype. This study used video supplemented by parent report data to describe the gross motor profile in females with Rett syndrome (n=99) and to investigate the impact of age, genotype, scoliosis and hand stereotypies. Factor analysis enabled the calculation of general and complex gross motor skills scores. Most subjects were able to sit, slightly less than half were able to walk and a minority were able to transfer without assistance. General gross motor skills declined with age and were poorer in those who had surgically treated scoliosis but not conservatively managed scoliosis. Complex gross motor skills did not decline with age and were better in those without scoliosis. Those with a p.R133C, p.R294X, or a p.R255X mutation appear to have better motor skills overall than those with a p.R270X or large deletion mutation. Motor scores were not related to the frequency of hand stereotypies. This information is useful for the clinician and family when planning support strategies and interventions.
2. Epstein T, Saltzman-Benaiah J, O’Hare A, Goll JC, Tuck S. {{Associated features of Asperger Syndrome and their relationship to parenting stress}}. {Child Care Health Dev};2008 (Jul);34(4):503-511.
BACKGROUND: Studies have shown an increased level of stress in parents of autistic children relative to parents of non-autistic children. Few studies have examined parenting stress specifically within the Asperger Syndrome (AS) population. Children with AS often have associated difficulties such as sensory sensitivities and problems with executive functioning (i.e. planning, inhibiting, shifting set). This study was designed to study parenting stress as well as to consider the relationship between parenting stress and some of the associated difficulties of AS. More specifically, the aims of this study were to demonstrate the following: that, as a group, parents of children with AS would report elevated levels of parenting stress, a finding which may be more significant for mothers than fathers; that children with AS show impairment in executive functioning as well as heightened sensory sensitivity according to parent report; that parent report of their child’s demanding characteristics would be positively associated with their self-reported levels of parenting stress. METHODS: Participants in this study were the parents of 39 children between the ages of 5 and 12 years, reflecting a 71% response rate, in the Lothian region of Scotland who completed The Parenting Stress Index, the Behavioural Rating Inventory of Executive Function and the Short Sensory Profile. RESULTS: The study revealed that both mothers and fathers of AS children reported elevated levels of parenting stress. There was a significant positive correlation between mother’s parenting stress and the child’s level of impairment, both with respect to executive dysfunction as well as sensory difficulties. CONCLUSION: The challenges of parenting a child with AS should not be underestimated. Further study is needed to explore the causative role that child impairments play in parenting stress and what types of interventions may prove most helpful to these families.
3. Gargus JJ. {{Genetic calcium signaling abnormalities in the central nervous system: seizures, migraine, and autism}}. {Ann N Y Acad Sci};2009 (Jan);1151:133-156.
The calcium ion is one of the most versatile, ancient, and universal of biological signaling molecules, known to regulate physiological systems at every level from membrane potential and ion transporters to kinases and transcription factors. Disruptions of intracellular calcium homeostasis underlie a host of emerging diseases, the calciumopathies. Cytosolic calcium signals originate either as extracellular calcium enters through plasma membrane ion channels or from the release of an intracellular store in the endoplasmic reticulum (ER) via inositol triphosphate receptor and ryanodine receptor channels. Therefore, to a large extent, calciumopathies represent a subset of the channelopathies, but include regulatory pathways and the mitochondria, the major intracellular calcium repository that dynamically participates with the ER stores in calcium signaling, thereby integrating cellular energy metabolism into these pathways, a process of emerging importance in the analysis of the neurodegenerative and neuropsychiatric diseases. Many of the calciumopathies are common complex polygenic diseases, but leads to their understanding come most prominently from rare monogenic channelopathy paradigms. Monogenic forms of common neuronal disease phenotypes-such as seizures, ataxia, and migraine-produce a constitutionally hyperexcitable tissue that is susceptible to periodic decompensations. The gene families and genetic lesions underlying familial hemiplegic migraine, FHM1/CACNA1A, FHM2/ATP1A2, and FHM3/SCN1A, and monogenic mitochondrial migraine syndromes, provide a robust platform from which genes, such as CACNA1C, which encodes the calcium channel mutated in Timothy syndrome, can be evaluated for their role in autism and bipolar disease.
4. Gauthier I, Klaiman C, Schultz RT. {{Face composite effects reveal abnormal face processing in Autism spectrum disorders}}. {Vision Res};2009 (Feb);49(4):470-478.
Although it has been suggested that individuals with an Autism spectrum disorder (ASD) process faces less holistically than typically developing controls, there are few direct investigations of this hypothesis. This question was addressed before using the composite paradigm (Teunisse, J. P., & de Gelder, B. (2003). Face processing in adolescents with autistic disorder: The inversion and composite effects. Brain Cognition, 52(3), 285-294.). The results had revealed that adolescents with ASDs were less sensitive than controls to the misalignment of face parts and it was concluded their face processing was less holistic. However, because of shortcomings of the design, it was not possible to distinguish whether individuals with Autism processed both aligned and misaligned composites in a part-based fashion, or both in a holistic fashion. We compared adolescents with ASDs to controls matched on sex, age and IQ on a more complete version of the composite paradigm. The results indicate that individuals with ASDs, like controls, experience interference from facial features that they are told to ignore. However, while such interference is released for controls if parts of face composites are misaligned, individuals with ASDs show comparable interference from irrelevant parts regardless of alignment. Two different interpretations are discussed, both compatible with the idea that perceptual and or attentional abnormalities in ASDs result in a diminished level of expertise for faces.
5. Guerini FR, Bolognesi E, Manca S, Sotgiu S, Zanzottera M, Agliardi C, Usai S, Clerici M. {{Family-based transmission analysis of HLA genetic markers in Sardinian children with autistic spectrum disorders}}. {Hum Immunol};2009 (Mar);70(3):184-190.
Analyses of a 6-Mb region spanning the human leukocyte antigen (HLA) region from the HLA-DR to the HFE gene were performed in 37 families of Sardinian ancestry, all of whom had at least one autistic child, to identify genetic markers associated with autism spectrum disorders (ASD) development. In particular, four microsatellites (MIB, D6S265, MOGc, and D6S2239) and three single-nucleotide polymorphisms (SNPs; two in positions -308 and -238 in the promoter of the TNF-alpha and SNP rs2857766 [V142L] in exon 3 of the MOG gene) were analyzed. An intrafamilial case-control method (affected family-based controls) and transmission disequilibrium test analysis were used to evaluate the association of microsatellite and SNP markers with ASD-affected children. Results indicated positive associations with ASD for D6S265*220 (p < 0.01) and MOGc*131 (p < 0.05) and negative associations for MOGc*117 and MIB*346 alleles (p < 0.01) in ASD children. Polymorphism haplotype analysis indicated that D6S265 allele *220 and MOGc allele *131 were significantly more likely to be transmitted together, as a whole haplotype, to ASD children (p < 0.05). Conversely, the D6S265*224-MOGc*117-rs2857766(G) haplotype was significantly less frequently transmitted to ASD children (p < 0.01). The results present novel gene markers, reinforcing the hypothesis that genetic factors play a pivotal role in the pathogenesis of ASD.
6. Herbrecht E, Poustka F, Birnkammer S, Duketis E, Schlitt S, Schmotzer G, Bolte S. {{Pilot evaluation of the Frankfurt Social Skills Training for children and adolescents with autism spectrum disorder}}. {Eur Child Adolesc Psychiatry};2009 (Jun);18(6):327-335.
The objective of this pilot study was to evaluate the effectiveness of a group-based intervention aiming at improving social and communication skills in individuals with autism spectrum disorder. Over a period of 11 months, N = 17 children and adolescents received treatment according to the manualised Frankfurt Social Skills Training (KONTAKT). Parent, teacher, expert and blind expert ratings were assessed to judge outcome regarding peer interaction, autistic behaviours, adaptive functioning and family burden. The participants exhibited improvements pre to follow-up treatment, particularly in the area of autistic symptomatology. Effect sizes (partial eta squared) ranged from 0.02 to 0.69. Among other things, regression models showed a positive influence of IQ and language skills on gains in social skills. Findings indicate that KONTAKT might be useful for enhancing social skills and reducing autism-related psychopathology over time in different contexts. Nevertheless, controlled trials are needed to reassure its effectiveness.
7. Mosconi MW, Kay M, D’Cruz AM, Seidenfeld A, Guter S, Stanford LD, Sweeney JA. {{Impaired inhibitory control is associated with higher-order repetitive behaviors in autism spectrum disorders}}. {Psychol Med};2009 (Sep);39(9):1559-1566.
BACKGROUND: Impairments in executive cognitive control, including a reduced ability to inhibit prepotent responses, have been reported in autism spectrum disorders (ASD). These deficits may underlie patterns of repetitive behaviors associated with the disorder. METHOD: Eighteen individuals with ASD and 15 age- and IQ-matched healthy individuals performed an antisaccade task and a visually guided saccade control task, each with gap and overlap conditions. Measures of repetitive behaviors were obtained using the Autism Diagnostic Inventory-Revised (ADI-R) and examined in relation to neurocognitive task performance. RESULTS: Individuals with an ASD showed increased rates of prosaccade errors (failures to inhibit prepotent responses) on the antisaccade task regardless of task condition (gap/overlap). Prosaccade error rates were associated with the level of higher-order (e.g. compulsions, preoccupations) but not sensorimotor repetitive behaviors in ASD. CONCLUSIONS: Neurocognitive disturbances in voluntary behavioral control suggest that alterations in frontostriatal systems contribute to higher-order repetitive behaviors in ASD.
8. Shultz SR, Macfabe DF, Martin S, Jackson J, Taylor R, Boon F, Ossenkopp KP, Cain DP. {{Intracerebroventricular injections of the enteric bacterial metabolic product propionic acid impair cognition and sensorimotor ability in the Long-Evans rat: further development of a rodent model of autism}}. {Behav Brain Res};2009 (Jun 8);200(1):33-41.
Propionic acid (PPA) is a dietary short chain fatty acid and a metabolic end-product of enteric bacteria. Intracerebroventricular (ICV) injections of PPA can result in brain and behavioral abnormalities in rats similar to those seen in humans suffering from autism. To evaluate cognition and sensorimotor ability in the PPA model, male Long-Evans hooded rats received ICV injection of PPA or control compounds prior to behavioral testing in water maze and beam tasks. Compared to controls, PPA-treated rats were impaired in the water maze task as indicated by an unusual pattern of mild or no impairment during spatial acquisition training, but marked impairment during spatial reversal training. PPA-treated rats were also impaired on the beam task. Neuropathological analysis from PPA-treated rats revealed an innate neuroinflammatory response. These findings add to evidence that PPA can change the brain and behavior in the laboratory rat consistent with symptoms of human autism.
9. Smith M, Spence MA, Flodman P. {{Nuclear and mitochondrial genome defects in autisms}}. {Ann N Y Acad Sci};2009 (Jan);1151:102-132.
In this review we will evaluate evidence that altered gene dosage and structure impacts neurodevelopment and neural connectivity through deleterious effects on synaptic structure and function, and evidence that the latter are key contributors to the risk for autism. We will review information on alterations of structure of mitochondrial DNA and abnormal mitochondrial function in autism and indications that interactions of the nuclear and mitochondrial genomes may play a role in autism pathogenesis. In a final section we will present data derived using Affymetrix SNP 6.0 microarray analysis of DNA of a number of subjects and parents recruited to our autism spectrum disorders project. We include data on two sets of monozygotic twins. Collectively these data provide additional evidence of nuclear and mitochondrial genome imbalance in autism and evidence of specific candidate genes in autism. We present data on dosage changes in genes that map on the X chromosomes and the Y chromosome. Precise analyses of Y located genes are often difficult because of the high degree of homology of X- and Y-related genes. However, continued efforts to analyze the latter are important, given the consistent evidence for a 4:1 ratio of males to females affected by autism. It is also important to consider whether environmental factors play a role in generating the nuclear and mitochondrial genomic instability we have observed. The study of autism will benefit from a move to analysis of pathways and multigene clusters for identification of subtypes that share a specific genetic etiology.
